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cdf50f463c668be65ea2db8af48c6bc0e55bd833 | wikidoc | ACVR1B | ACVR1B
Activin receptor type-1B is a protein that in humans is encoded by the ACVR1B gene.
ACVR1B or ALK-4 acts as a transducer of activin or activin like ligands (e.g., inhibin) signals. Activin binds to either ACVR2A or ACVR2B and then forms a complex with ACVR1B. These go on to recruit the R-SMADs SMAD2 or SMAD3. ACVR1B also transduces signals of nodal, GDF-1, and Vg1; however, unlike activin, they require other coreceptor molecules such as the protein Cripto.
# Function
Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I (I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with a cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling, and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in phosphorylation of type I receptors by type II receptors. This gene encodes activin A type IB receptor, composed of 11 exons. Alternative splicing and alternative polyadenylation result in 3 fully described transcript variants. The mRNA expression of variants 1, 2, and 3 is confirmed, and a potential fourth variant contains an alternative exon 8 and lacks exons 9 through 11, but its mRNA expression has not been confirmed.
# Interactions
ACVR1B has been shown to interact with
- ACVR2A, and ACVR2B | ACVR1B
Activin receptor type-1B is a protein that in humans is encoded by the ACVR1B gene.[1][2]
ACVR1B or ALK-4 acts as a transducer of activin or activin like ligands (e.g., inhibin) signals. Activin binds to either ACVR2A or ACVR2B and then forms a complex with ACVR1B. These go on to recruit the R-SMADs SMAD2 or SMAD3.[3] ACVR1B also transduces signals of nodal, GDF-1, and Vg1; however, unlike activin, they require other coreceptor molecules such as the protein Cripto.[4]
# Function
Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I (I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with a cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling, and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in phosphorylation of type I receptors by type II receptors. This gene encodes activin A type IB receptor, composed of 11 exons. Alternative splicing and alternative polyadenylation result in 3 fully described transcript variants. The mRNA expression of variants 1, 2, and 3 is confirmed, and a potential fourth variant contains an alternative exon 8 and lacks exons 9 through 11, but its mRNA expression has not been confirmed.[2]
# Interactions
ACVR1B has been shown to interact with
- ACVR2A,[5][6] and ACVR2B[7][5] | https://www.wikidoc.org/index.php/ACVR1B | |
c1b4e7caeb25429386f8529cb00c89dcc93f4340 | wikidoc | ACVR1C | ACVR1C
The activin A receptor also known as ACVR1C or ALK-7 is a protein that in humans is encoded by the ACVR1C gene. ACVR1C is a type I receptor for the TGFB family of signaling molecules.
ACVR1C transduces signals of Nodal. Nodal binds to ACVR2B and then forms a complex with ACVR1C. These go on to recruit the R-SMADs SMAD2 or SMAD3.
Upon ligand binding, type I receptors phosphorylate cytoplasmic SMAD family transcription factors, which then translocate to the nucleus and interact directly with DNA or in complex with other transcription factors. | ACVR1C
The activin A receptor also known as ACVR1C or ALK-7 is a protein that in humans is encoded by the ACVR1C gene.[1] ACVR1C is a type I receptor for the TGFB family of signaling molecules.[1]
ACVR1C transduces signals of Nodal. Nodal binds to ACVR2B and then forms a complex with ACVR1C. These go on to recruit the R-SMADs SMAD2 or SMAD3.[2]
Upon ligand binding, type I receptors phosphorylate cytoplasmic SMAD family transcription factors, which then translocate to the nucleus and interact directly with DNA or in complex with other transcription factors.[1] | https://www.wikidoc.org/index.php/ACVR1C | |
807b22d7ca6ec20a01d6fe5333bfe73ab0bbbbe9 | wikidoc | ACVRL1 | ACVRL1
Serine/threonine-protein kinase receptor R3 is an enzyme that in humans is encoded by the ACVRL1 gene.
ACVRL1 is a receptor in the TGF beta signaling pathway. It is also known as activin receptor-like kinase 1, or ALK1.
# Function
This gene encodes a type I cell-surface receptor for the TGF-beta superfamily of ligands. It shares with other type I receptors a high degree of similarity in serine-threonine kinase subdomains, a glycine- and serine-rich region (called the GS domain) preceding the kinase domain, and a short C-terminal tail. The encoded protein, sometimes termed ALK1, shares similar domain structures with other closely related ALK or activin receptor-like kinase proteins that form a subfamily of receptor serine/threonine kinases. Mutations in this gene are associated with hemorrhagic telangiectasia type 2, also known as Rendu-Osler-Weber syndrome 2.
# Pathology
Germline mutations of ACVRL1 are associated with:
- hereditary hemorrhagic telangiectasia type 2 (Rendu-Osler-Weber syndrome 2)
- Pulmonary arteriovenous malformations
Somatic mosaicism in ACVRL1 are associated with severe pulmonary arterial hypertension.
ACVRL1 directly interacts with low-density lipoprotein (LDL), which implies that it might initiate the early phases of atherosclerosis.
# As a drug target
- Dalantercept is an experimental ALK1 inhibitor.
# Closely/family related kinases
(Not to be confused with anaplastic lymphoma kinase (ALK) )
ALK4 is ACVR1B, ALK7 is ACVR1C, and ALK5 is the TGF-β type I receptor. | ACVRL1
Serine/threonine-protein kinase receptor R3 is an enzyme that in humans is encoded by the ACVRL1 gene.[1][2][3]
ACVRL1 is a receptor in the TGF beta signaling pathway. It is also known as activin receptor-like kinase 1, or ALK1.
# Function
This gene encodes a type I cell-surface receptor for the TGF-beta superfamily of ligands. It shares with other type I receptors a high degree of similarity in serine-threonine kinase subdomains, a glycine- and serine-rich region (called the GS domain) preceding the kinase domain, and a short C-terminal tail. The encoded protein, sometimes termed ALK1, shares similar domain structures with other closely related ALK or activin receptor-like kinase proteins that form a subfamily of receptor serine/threonine kinases. Mutations in this gene are associated with hemorrhagic telangiectasia type 2, also known as Rendu-Osler-Weber syndrome 2.[3]
# Pathology
Germline mutations of ACVRL1 are associated with:
- hereditary hemorrhagic telangiectasia type 2 (Rendu-Osler-Weber syndrome 2)[4]
- Pulmonary arteriovenous malformations[5]
Somatic mosaicism in ACVRL1 are associated with severe pulmonary arterial hypertension.[6]
ACVRL1 directly interacts with low-density lipoprotein (LDL), which implies that it might initiate the early phases of atherosclerosis.[7]
# As a drug target
- Dalantercept is an experimental ALK1 inhibitor.[8]
# Closely/family related kinases
(Not to be confused with anaplastic lymphoma kinase (ALK) )
ALK4 is ACVR1B, ALK7 is ACVR1C, and ALK5 is [part of] the TGF-β type I receptor.[9] | https://www.wikidoc.org/index.php/ACVRL1 | |
1adaf93801d71e22452d57596ecd30e609f9d3a5 | wikidoc | ADAM10 | ADAM10
A Disintegrin and metalloproteinase domain-containing protein 10, also known as ADAM10 or CDw156 or CD156c is a protein that in humans is encoded by the ADAM10 gene.
# Function
Members of the ADAM family are cell surface proteins with a unique structure possessing both potential adhesion and protease domains. Sheddase, a generic name for the ADAM metallopeptidase, functions primarily to cleave membrane proteins at the cellular surface. Once cleaved, the sheddases release soluble ectodomains with an altered location and function.
Although a single sheddase may “shed” a variety of substances, multiple sheddases can cleave the same substrate resulting in different consequences.This gene encodes an ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin.
ADAM10 (EC#: 3.4.24.81) is a sheddase, and has a broad specificity for peptide hydrolysis reactions.
ADAM10 cleaves ephrin, within the ephrin/eph complex, formed between two cell surfaces. When ephrin is freed from the opposing cell, the entire ephrin/eph complex is endocytosed. This shedding in trans had not been previously shown, but may well be involved in other shedding events.
In neurons, ADAM10 is the most important enzyme with α-secretase activity for proteolytic processing of the amyloid precursor protein.
# Structure
Although no crystallographic x-ray diffraction analyses have been published that depict the entire structure of ADAM10, one domain has been studied using this technique. The disintigrin and cysteine-rich domain (shown to the right) plays an essential role in regulation of protease activity in vivo. Recent experimental evidence suggests that this region, which is distinct from the active site, may be responsible for substrate specificity of the enzyme. It is proposed that this domain binds to particular regions of the enzyme’s substrate, allowing peptide bond hydrolysis to occur in well defined locations on certain substrate proteins.
The proposed active site of ADAM10 has been identified by sequence analysis, and is identical to enzymes in the Snake Venom metalloprotein domain family. The consensus sequence for catalytically active ADAM proteins is HEXGHNLGXXHD. Structural analysis of ADAM17, which has the same active site sequence as ADAM10, suggests that the three histidines in this sequence bind a Zn2+ atom, and that the glutamate is the catalytic residue.
# Catalytic Mechanism
Although the exact mechanism of ADAM10 has not been thoroughly investigated, its active site is homologous to those of well studied zinc-proteases such as carboxypeptidase A and thermolysin. Therefore, it is proposed that ADAM10 utilizes a similar mechanism as these enzymes.
In zinc proteases, the key catalytic elements have been identified as a glutamate residue and a Zn2+ ion coordinated to histidine residues.
The proposed mechanism begins with deprotonation of a water molecule by glutamate. The resultant hydroxide initiates a nucleophillic attack on a carbonyl carbon on the peptide backbone, producing a tetrahedral intermediate. This step is facilitated by electron withdrawal from oxygen by Zn2+ and by zinc’s subsequent stabilization of the negative charge on the oxygen atom in the intermediate state. As electrons move down from the oxygen atom to re-form the double bond, the tetrahedral intermediate collapses to products with protonation of -NH by the glutamate residue.
# Clinical significance
## Interaction with the malaria parasite
A number of different proteins on the surface of Plasmodium falciparum malaria parasites help the invaders bind to red blood cells. But once attached to host blood cells, the parasites need to shed the 'sticky' surface proteins that would otherwise interfere with entrance into the cell. The Sheddase enzyme, specifically called PfSUB2 in this example, is required for the parasites to invade cells; without it, the parasites die. The sheddase is stored in and released from cellular compartments near the tip of the parasite, according to the study. Once on the surface, the enzyme attaches to a motor that shuttles it from front to back, liberating the sticky surface proteins. With these proteins removed, the parasite gains entrance into a red blood cell. The entire invasion lasts about 30 seconds and without this ADAM metallopeptidase, malaria would be ineffective at invading the red blood cells.
# Breast cancer
In combination with low doses of herceptin, selective ADAM10 inhibitors decrease proliferation in HER2 over-expressing cell lines while inhibitors, that do not inhibit ADAM10, have no impact. These results are consistent with ADAM10 being a major determinant of HER2 shedding, the inhibition of which, may provide a novel therapeutic approach for treating breast cancer and a variety of other cancers with active HER2 signaling.
The presence of the product of this gene in neuronal synapses in conjunction with protein AP2 has been seen in increased amounts in the hippocampal neurons of Alzheimer's disease patients. | ADAM10
A Disintegrin and metalloproteinase domain-containing protein 10, also known as ADAM10 or CDw156 or CD156c is a protein that in humans is encoded by the ADAM10 gene.[1]
# Function
Members of the ADAM family are cell surface proteins with a unique structure possessing both potential adhesion and protease domains. Sheddase, a generic name for the ADAM metallopeptidase, functions primarily to cleave membrane proteins at the cellular surface. Once cleaved, the sheddases release soluble ectodomains with an altered location and function.[2][3][4]
Although a single sheddase may “shed” a variety of substances, multiple sheddases can cleave the same substrate resulting in different consequences.This gene encodes an ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin.[1]
ADAM10 (EC#: 3.4.24.81) is a sheddase, and has a broad specificity for peptide hydrolysis reactions.[5]
ADAM10 cleaves ephrin, within the ephrin/eph complex, formed between two cell surfaces. When ephrin is freed from the opposing cell, the entire ephrin/eph complex is endocytosed. This shedding in trans had not been previously shown, but may well be involved in other shedding events.[6]
In neurons, ADAM10 is the most important enzyme with α-secretase activity for proteolytic processing of the amyloid precursor protein.[7]
# Structure
Although no crystallographic x-ray diffraction analyses have been published that depict the entire structure of ADAM10, one domain has been studied using this technique. The disintigrin and cysteine-rich domain (shown to the right) plays an essential role in regulation of protease activity in vivo. Recent experimental evidence suggests that this region, which is distinct from the active site, may be responsible for substrate specificity of the enzyme. It is proposed that this domain binds to particular regions of the enzyme’s substrate, allowing peptide bond hydrolysis to occur in well defined locations on certain substrate proteins.[8]
The proposed active site of ADAM10 has been identified by sequence analysis, and is identical to enzymes in the Snake Venom metalloprotein domain family. The consensus sequence for catalytically active ADAM proteins is HEXGHNLGXXHD. Structural analysis of ADAM17, which has the same active site sequence as ADAM10, suggests that the three histidines in this sequence bind a Zn2+ atom, and that the glutamate is the catalytic residue.[9]
# Catalytic Mechanism
Although the exact mechanism of ADAM10 has not been thoroughly investigated, its active site is homologous to those of well studied zinc-proteases such as carboxypeptidase A and thermolysin. Therefore, it is proposed that ADAM10 utilizes a similar mechanism as these enzymes.
In zinc proteases, the key catalytic elements have been identified as a glutamate residue and a Zn2+ ion coordinated to histidine residues.[10]
The proposed mechanism begins with deprotonation of a water molecule by glutamate. The resultant hydroxide initiates a nucleophillic attack on a carbonyl carbon on the peptide backbone, producing a tetrahedral intermediate. This step is facilitated by electron withdrawal from oxygen by Zn2+ and by zinc’s subsequent stabilization of the negative charge on the oxygen atom in the intermediate state. As electrons move down from the oxygen atom to re-form the double bond, the tetrahedral intermediate collapses to products with protonation of -NH by the glutamate residue.[10]
# Clinical significance
## Interaction with the malaria parasite
A number of different proteins on the surface of Plasmodium falciparum malaria parasites help the invaders bind to red blood cells. But once attached to host blood cells, the parasites need to shed the 'sticky' surface proteins that would otherwise interfere with entrance into the cell. The Sheddase enzyme, specifically called PfSUB2 in this example, is required for the parasites to invade cells; without it, the parasites die. The sheddase is stored in and released from cellular compartments near the tip of the parasite, according to the study. Once on the surface, the enzyme attaches to a motor that shuttles it from front to back, liberating the sticky surface proteins. With these proteins removed, the parasite gains entrance into a red blood cell. The entire invasion lasts about 30 seconds and without this ADAM metallopeptidase, malaria would be ineffective at invading the red blood cells.[11]
# Breast cancer
In combination with low doses of herceptin, selective ADAM10 inhibitors decrease proliferation in HER2 over-expressing cell lines while inhibitors, that do not inhibit ADAM10, have no impact. These results are consistent with ADAM10 being a major determinant of HER2 shedding, the inhibition of which, may provide a novel therapeutic approach for treating breast cancer and a variety of other cancers with active HER2 signaling.[12]
The presence of the product of this gene in neuronal synapses in conjunction with protein AP2 has been seen in increased amounts in the hippocampal neurons of Alzheimer's disease patients.[13] | https://www.wikidoc.org/index.php/ADAM10 | |
85ae67a6696210f9b4bb5bc27196115172cd08f8 | wikidoc | ADAM12 | ADAM12
Disintegrin and metalloproteinase domain-containing protein 12 is an enzyme that in humans is encoded by the ADAM12 gene. ADAM12 has two splice variants: ADAM12-L, the long form, has a transmembrane region and ADAM12-S, a shorter variant, is soluble and lacks the transmembrane and cytoplasmic domains.
# Function
This gene encodes a member of the ADAM (a disintegrin and metalloprotease) protein family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This gene has two alternatively spliced transcripts: a shorter secreted form and a longer membrane-bound form. The shorter form is found to stimulate myogenesis.
# Clinical Significance
ADAM 12, a metalloprotease that binds insulin growth factor binding protein-3 (IGFBP-3), appears to be an effective early Down syndrome marker. Decreased levels of ADAM 12 may be detected in cases of trisomy 21 as early as 8 to 10 weeks gestation. Maternal serum ADAM 12 and PAPP-A levels at 8 to 9 weeks gestation in combination with maternal age yielded a 91% detection rate for Down syndrome at a 5% false-positive rate. When nuchal translucency data from approximately 12 weeks gestation was added, this increased the detection rate to 97%.
ADAM12 has also been implicated in the development of pathology in various cancers, hypertension, liver fibrogenesis, and asthma. In asthma, ADAM12 is upregulated in lung epithelium in response to TNF-alpha.
# Interactions
ADAM12 has been shown to interact with:
- ACTN2,
- IGFBP3, and
- PIK3R1. | ADAM12
Disintegrin and metalloproteinase domain-containing protein 12 is an enzyme that in humans is encoded by the ADAM12 gene.[1][2] ADAM12 has two splice variants: ADAM12-L, the long form, has a transmembrane region and ADAM12-S, a shorter variant, is soluble and lacks the transmembrane and cytoplasmic domains.[3]
# Function
This gene encodes a member of the ADAM (a disintegrin and metalloprotease) protein family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This gene has two alternatively spliced transcripts: a shorter secreted form and a longer membrane-bound form. The shorter form is found to stimulate myogenesis.[4]
# Clinical Significance
ADAM 12, a metalloprotease that binds insulin growth factor binding protein-3 (IGFBP-3), appears to be an effective early Down syndrome marker. Decreased levels of ADAM 12 may be detected in cases of trisomy 21 as early as 8 to 10 weeks gestation. Maternal serum ADAM 12 and PAPP-A levels at 8 to 9 weeks gestation in combination with maternal age yielded a 91% detection rate for Down syndrome at a 5% false-positive rate. When nuchal translucency data from approximately 12 weeks gestation was added, this increased the detection rate to 97%.[5]
ADAM12 has also been implicated in the development of pathology in various cancers, hypertension, liver fibrogenesis, and asthma.[6] In asthma, ADAM12 is upregulated in lung epithelium in response to TNF-alpha.[7]
# Interactions
ADAM12 has been shown to interact with:
- ACTN2,[8]
- IGFBP3,[9][10] and
- PIK3R1.[11] | https://www.wikidoc.org/index.php/ADAM12 | |
a3f0c12bacdc2232fdab320d319c594f269aa7a7 | wikidoc | ADAM15 | ADAM15
Disintegrin and metalloproteinase domain-containing protein 15 is an enzyme that in humans is encoded by the ADAM15 gene.
# Function
The protein encoded by this gene is a member of the ADAM (a disintegrin and metalloproteinase) protein family. ADAM family members are type I transmembrane glycoproteins known to be involved in cell adhesion and proteolytic ectodomain processing of cytokines and adhesion molecules. This protein contains multiple functional domains including a zinc-binding metalloprotease domain, a disintegrin-like domain, as well as an EGF-like domain. Through its disintegrin-like domain, this protein specifically interacts with the integrin beta chain, beta 3. It also interacts with Src family protein-tyrosine kinases in a phosphorylation-dependent manner, suggesting that this protein may function in cell-cell adhesion as well as in cellular signaling. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed.
# Clinical significance
## Arthritis
ADAM15 has been associated with a number of diseases, most recently Rheumatoid Arthritis where it is required for the activation of the FAK and Src pathways to generate apoptosis resistance in response to apoptotic signalling or cell stress. ADAM15 also has an antiapoptotic effect in osteoarthritic chondrocytes.
## Cancer
The precise role of ADAM15 in cancer is still unclear but the metalloprotein has been linked to a number of different cancerous diseases such as Breast cancer where the expression of the protein is increased in carcinoma in-situ, invasive carcinoma and metastatic breast cancer tissues Additionally, the alternative splice variant forms of ADAM15 have also been correlated with different prognosis in 48 breast cancer patients based upon their expression levels. ADAM15 has also been shown to have a role in Prostate Cancer again through increased expression in neoplastic and metastatic tissues compared to normal prostate tissues and also through its modulation of epithelial cell- tumour cell interactions.
# Interactions
ADAM15 has been shown to interact with:
- Grb2,
- HCK,
- Lck and
- SH3GL2, and
- SNX9.
The alternatively spliced isoforms have also been shown to exhibit different preferential interactions with proteins containing SH3 domains. | ADAM15
Disintegrin and metalloproteinase domain-containing protein 15 is an enzyme that in humans is encoded by the ADAM15 gene.[1]
# Function
The protein encoded by this gene is a member of the ADAM (a disintegrin and metalloproteinase) protein family. ADAM family members are type I transmembrane glycoproteins known to be involved in cell adhesion and proteolytic ectodomain processing of cytokines and adhesion molecules. This protein contains multiple functional domains including a zinc-binding metalloprotease domain, a disintegrin-like domain, as well as an EGF-like domain. Through its disintegrin-like domain, this protein specifically interacts with the integrin beta chain, beta 3. It also interacts with Src family protein-tyrosine kinases in a phosphorylation-dependent manner, suggesting that this protein may function in cell-cell adhesion as well as in cellular signaling. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed.[2]
# Clinical significance
## Arthritis
ADAM15 has been associated with a number of diseases, most recently Rheumatoid Arthritis where it is required for the activation of the FAK and Src pathways to generate apoptosis resistance in response to apoptotic signalling or cell stress.[3] ADAM15 also has an antiapoptotic effect in osteoarthritic chondrocytes.[4]
## Cancer
The precise role of ADAM15 in cancer is still unclear but the metalloprotein has been linked to a number of different cancerous diseases such as Breast cancer where the expression of the protein is increased in carcinoma in-situ, invasive carcinoma and metastatic breast cancer tissues[5] Additionally, the alternative splice variant forms of ADAM15 have also been correlated with different prognosis in 48 breast cancer patients based upon their expression levels.[6] ADAM15 has also been shown to have a role in Prostate Cancer again through increased expression in neoplastic and metastatic tissues compared to normal prostate tissues[5] and also through its modulation of epithelial cell- tumour cell interactions.[7]
# Interactions
ADAM15 has been shown to interact with:
- Grb2,[8]
- HCK,[8]
- Lck[8] and
- SH3GL2,[9] and
- SNX9.[9]
The alternatively spliced isoforms have also been shown to exhibit different preferential interactions with proteins containing SH3 domains.[6][10] | https://www.wikidoc.org/index.php/ADAM15 | |
0ba8f0f0727bc271a61f9a00c051d6fef5c48565 | wikidoc | ADAM17 | ADAM17
ADAM metallopeptidase domain 17 (ADAM17), also called TACE (tumor necrosis factor-α-converting enzyme), is a 70-kDa enzyme that belongs to the ADAM protein family of disintegrins and metalloproteases.
# Chemical characteristics
ADAM17 is an 824-amino acid polypeptide.
# Function
ADAM17 is understood to be involved in the processing of tumor necrosis factor alpha (TNF-α) at the surface of the cell, and from within the intracellular membranes of the trans-Golgi network. This process, which is also known as 'shedding', involves the cleavage and release of a soluble ectodomain from membrane-bound pro-proteins (such as pro-TNF-α), and is of known physiological importance. ADAM17 was the first 'sheddase' to be identified, and is also understood to play a role in the release of a diverse variety of membrane-anchored cytokines, cell adhesion molecules, receptors, ligands, and enzymes.
Cloning of the TNF-α gene revealed it to encode a 26 kDa type II transmembrane pro-polypeptide that becomes inserted into the cell membrane during its maturation. At the cell surface, pro-TNF-α is biologically active, and is able to induce immune responses via juxtacrine intercellular signaling. However, pro-TNF-α can undergo a proteolytic cleavage at its Ala76-Val77 amide bond, which releases a soluble 17kDa extracellular domain (ectodomain) from the pro-TNF-α molecule. This soluble ectodomain is the cytokine commonly known as TNF-α, which is of pivotal importance in paracrine signaling. This proteolytic liberation of soluble TNF-α is catalyzed by ADAM17.
Recently, ADAM17 was discovered as a crucial mediator of resistance to radiotherapy. Radiotherapy can induce a dose-dependent increase of furin-mediated cleavage of the ADAM17 proform to active ADAM17, which results in enhanced ADAM17 activity in vitro and in vivo. It was also shown that radiotherapy activates ADAM17 in non-small cell lung cancer, which results in shedding of multiple survival factors, growth factor pathway activation, and radiotherapy-induced treatment resistance.
ADAM17 may play a prominent role in the Notch signaling pathway, during the proteolytic release of the Notch intracellular domain (from the Notch1 receptor) that occurs following ligand binding. ADAM17 also regulates the MAP kinase signaling pathway by regulating shedding of the EGFR ligand amphiregulin in the mammary gland. ADAM17 also has a role in the shedding of L-selectin, a cellular adhesion molecule.
# Interactions
ADAM17 has been shown to interact with:
- DLG1
- MAD2L1, and
- MAPK1.
# Cellular localization
The localization of ADAM17 is speculated to be an important determinant of shedding activity. TNF-α processing has classically been understood to occur in the trans-Golgi network, and be closely connected to transport of soluble TNF-α to the cell surface. However, research that suggests that the majority of mature, endogenous ADAM17 may be localized to a perinuclear compartment, with only a small amount of TACE being present on the cell surface. The localization of mature ADAM17 to a perinuclear compartment, therefore, raises the possibility that ADAM17-mediated ectodomain shedding may also occur in the intracellular environment, in contrast with the conventional model.
Functional ADAM17 has been documented to be ubiquitously expressed in the human colon, with increased activity in the colonic mucosa of patients with ulcerative colitis, a main form of inflammatory bowel disease. Other experiments have also suggested that expression of ADAM17 may be inhibited by ethanol.
# Model organisms
Model organisms have been used in the study of ADAM17 function. A conditional knockout mouse line, called Adam17tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty eight tests were carried out on mutant mice and two significant abnormalities were observed. Few homozygous mutant embryos were identified during gestation. The remaining tests were carried out on heterozygous mutant adult mice; an increased bone mineral content was observed in these animals using Micro-CT. | ADAM17
ADAM metallopeptidase domain 17 (ADAM17), also called TACE (tumor necrosis factor-α-converting enzyme), is a 70-kDa enzyme that belongs to the ADAM protein family of disintegrins and metalloproteases.
# Chemical characteristics
ADAM17 is an 824-amino acid polypeptide.[1][2]
# Function
ADAM17 is understood to be involved in the processing of tumor necrosis factor alpha (TNF-α) at the surface of the cell, and from within the intracellular membranes of the trans-Golgi network. This process, which is also known as 'shedding', involves the cleavage and release of a soluble ectodomain from membrane-bound pro-proteins (such as pro-TNF-α), and is of known physiological importance. ADAM17 was the first 'sheddase' to be identified, and is also understood to play a role in the release of a diverse variety of membrane-anchored cytokines, cell adhesion molecules, receptors, ligands, and enzymes.
Cloning of the TNF-α gene revealed it to encode a 26 kDa type II transmembrane pro-polypeptide that becomes inserted into the cell membrane during its maturation. At the cell surface, pro-TNF-α is biologically active, and is able to induce immune responses via juxtacrine intercellular signaling. However, pro-TNF-α can undergo a proteolytic cleavage at its Ala76-Val77 amide bond, which releases a soluble 17kDa extracellular domain (ectodomain) from the pro-TNF-α molecule. This soluble ectodomain is the cytokine commonly known as TNF-α, which is of pivotal importance in paracrine signaling. This proteolytic liberation of soluble TNF-α is catalyzed by ADAM17.
Recently, ADAM17 was discovered as a crucial mediator of resistance to radiotherapy. Radiotherapy can induce a dose-dependent increase of furin-mediated cleavage of the ADAM17 proform to active ADAM17, which results in enhanced ADAM17 activity in vitro and in vivo. It was also shown that radiotherapy activates ADAM17 in non-small cell lung cancer, which results in shedding of multiple survival factors, growth factor pathway activation, and radiotherapy-induced treatment resistance. [3]
ADAM17 may play a prominent role in the Notch signaling pathway, during the proteolytic release of the Notch intracellular domain (from the Notch1 receptor) that occurs following ligand binding. ADAM17 also regulates the MAP kinase signaling pathway by regulating shedding of the EGFR ligand amphiregulin in the mammary gland.[4] ADAM17 also has a role in the shedding of L-selectin, a cellular adhesion molecule.[5]
# Interactions
ADAM17 has been shown to interact with:
- DLG1[6]
- MAD2L1,[7][8] and
- MAPK1.[9]
# Cellular localization
The localization of ADAM17 is speculated to be an important determinant of shedding activity. TNF-α processing has classically been understood to occur in the trans-Golgi network, and be closely connected to transport of soluble TNF-α to the cell surface. However, research that suggests that the majority of mature, endogenous ADAM17 may be localized to a perinuclear compartment, with only a small amount of TACE being present on the cell surface. The localization of mature ADAM17 to a perinuclear compartment, therefore, raises the possibility that ADAM17-mediated ectodomain shedding may also occur in the intracellular environment, in contrast with the conventional model.
Functional ADAM17 has been documented to be ubiquitously expressed in the human colon, with increased activity in the colonic mucosa of patients with ulcerative colitis, a main form of inflammatory bowel disease. Other experiments have also suggested that expression of ADAM17 may be inhibited by ethanol.[10]
# Model organisms
Model organisms have been used in the study of ADAM17 function. A conditional knockout mouse line, called Adam17tm1a(EUCOMM)Wtsi[16][17] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[18][19][20]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[14][21] Twenty eight tests were carried out on mutant mice and two significant abnormalities were observed.[14] Few homozygous mutant embryos were identified during gestation. The remaining tests were carried out on heterozygous mutant adult mice; an increased bone mineral content was observed in these animals using Micro-CT.[14] | https://www.wikidoc.org/index.php/ADAM17 | |
c70c5c30dfa9bd701eda08819786d92770c12d6a | wikidoc | ADARB1 | ADARB1
Double-stranded RNA-specific editase 1 is an enzyme that in humans is encoded by the ADARB1 gene.
# Function
This gene encodes the enzyme responsible for pre-mRNA editing of the glutamate receptor subunit B by site-specific deamination of adenosines. Studies in rats found that this enzyme acted on its own pre-mRNA molecules to convert an AA dinucleotide to an AI dinucleotide which resulted in a new splice site. Alternative splicing of this gene results in several transcript variants, some of which have been characterized by the presence or absence of an ALU cassette insert and a short or long C-terminal region.
ADARB1 (ADAR2) requires the small molecule inositol hexakisphosphate (IP6) for proper function. ADAR2 is an A-to-I RNA-editing enzyme that mostly acts on protein-coding substrates. | ADARB1
Double-stranded RNA-specific editase 1 is an enzyme that in humans is encoded by the ADARB1 gene.[1][2][3]
# Function
This gene encodes the enzyme responsible for pre-mRNA editing of the glutamate receptor subunit B by site-specific deamination of adenosines. Studies in rats found that this enzyme acted on its own pre-mRNA molecules to convert an AA dinucleotide to an AI dinucleotide which resulted in a new splice site. Alternative splicing of this gene results in several transcript variants, some of which have been characterized by the presence or absence of an ALU cassette insert and a short or long C-terminal region.[3]
ADARB1 (ADAR2) requires the small molecule inositol hexakisphosphate (IP6) for proper function.[4] ADAR2 is an A-to-I RNA-editing enzyme that mostly acts on protein-coding substrates.[5] | https://www.wikidoc.org/index.php/ADARB1 | |
3f7f032e457d7e2d14591b29bc842f58c2d67035 | wikidoc | ADARB2 | ADARB2
Double-stranded RNA-specific editase B2 is an enzyme that in humans is encoded by the ADARB2 gene.
# Function
RNA-editing deaminase-2 (RED2, or ADARB2) is a member of the double-stranded RNA (dsRNA) adenosine deaminase family of RNA-editing enzymes. Adenosine deamination of pre-mRNA results in a change in the amino acid sequence of the gene product, which differs from that predicted by the genomic DNA sequence. Other members of this family include DRADA (ADAR) and RED1 (ADARB1).
Unlike ADAR1 and ADAR2, ADAR3 has demonstrated no editing ability in vitro. It has been shown to suppress 5-HT2C RNA editing in vitro through a yet unknown mechanism, and may thus work as a negative regulator. | ADARB2
Double-stranded RNA-specific editase B2 is an enzyme that in humans is encoded by the ADARB2 gene.[1][2][3]
# Function
RNA-editing deaminase-2 (RED2, or ADARB2) is a member of the double-stranded RNA (dsRNA) adenosine deaminase family of RNA-editing enzymes. Adenosine deamination of pre-mRNA results in a change in the amino acid sequence of the gene product, which differs from that predicted by the genomic DNA sequence. Other members of this family include DRADA (ADAR) and RED1 (ADARB1).[1][3]
Unlike ADAR1 and ADAR2, ADAR3 has demonstrated no editing ability in vitro. It has been shown to suppress 5-HT2C RNA editing in vitro through a yet unknown mechanism, and may thus work as a negative regulator.[4] | https://www.wikidoc.org/index.php/ADARB2 | |
e858dab5c5097817b17264405da99a3cc6a36b90 | wikidoc | ADCY10 | ADCY10
Adenylyl cyclase 10 also known as ADCY10 is an enzyme that, in humans, is encoded by the ADCY10 gene.
# Function
The protein encoded by this gene belongs to a distinct class of mammalian adenylyl cyclase that is soluble and insensitive to G protein or forskolin regulation. It is localized in the cytoplasm and is thought to function as a general bicarbonate sensor throughout the body. It may also play an important role in the generation of cAMP in spermatozoa, implying possible roles in sperm maturation through the epididymis, capacitation, hypermotility, and/or the acrosome reaction.
# Clinical significance
Mutations in the ADCY10 gene are associated with an increased risk of adsorptive hypercalciuria. | ADCY10
Adenylyl cyclase 10 also known as ADCY10 is an enzyme that, in humans, is encoded by the ADCY10 gene.[1]
# Function
The protein encoded by this gene belongs to a distinct class of mammalian adenylyl cyclase that is soluble and insensitive to G protein or forskolin regulation. It is localized in the cytoplasm and is thought to function as a general bicarbonate sensor throughout the body. It may also play an important role in the generation of cAMP in spermatozoa, implying possible roles in sperm maturation through the epididymis, capacitation, hypermotility, and/or the acrosome reaction.[2]
# Clinical significance
Mutations in the ADCY10 gene are associated with an increased risk of adsorptive hypercalciuria.[1] | https://www.wikidoc.org/index.php/ADCY10 | |
8eb78f603fd4f54b4812b777ef25db274ce4f0fe | wikidoc | AFP-L3 | AFP-L3
# Overview
In oncology, AFP-L3 is an isoform of Alpha-fetoprotein (AFP), a substance typically used in the triple test during pregnancy and for screening chronic liver disease patients for hepatocellular carcinoma (HCC). AFP can be fractionated by affinity electrophoresis into 3 glycoforms: L1, L2, and L3 based on the reactivity with the lectin Lens culinaris agglutinin (LCA). AFP-L3 binds strongly to LCA via an additional α 1-6 fucose residue attached at the reducing terminus of N-acetylglucosamine; this is in contrast to the L1 isoform. It is the L1 isoform which is typically associated with non-HCC inflammation of liver disease condition. The L3 isoform is specific to malignant tumors and its detected presence can serve to identify patients whom need increased monitoring for the development of HCC in high risk populations (i.e. chronic hepatitis B & C and/or liver cirrhosis). AFP-L3% is now being considered as a tumor marker for the North American demographic.
# AFP-L3% assay
AFP-L3 is isolated via an immunoassay and quantified using chemiluminesence on an automated platform. Results for AFP-L3 are represented as a ratio of LCA-reactive AFP to total AFP (AFP-L3%). The AFP-L3% assay, a liquid-phase binding assay, will help to identify at-risk subjects earlier, allowing for more intense evaluation for evidence of HCC according to existing practice guidelines in oncology. AFP-L3% is the standard for quantifying the L3 isoform of AFP in serum of high risk chronic liver disease (CLD) patients. Studies have shown that AFP-L3% test results of more than 10% can be indicative of early HCC or early nonseminomatous germ cell tumor.
Early testimonials from hepatologists indicate that there is a target patient population for the AFP-L3% assay. This target population are those CLD patients who have AFP concentrations in the indeterminate range of 20-200+ ng/mL and a small or indeterminate mass on imaging. It is in this range that doctors experience trouble differentiating non-HCC fluctuations in AFP vs indication of HCC. In such patients these hepatologists recommend utilizing AFP-L3% to clarify the disease state. Some hepatologists also use a positive result to urge insurance companies to pay for more frequent and intensive imaging.
Ultimately AFP-L3% may be used as a rule-in or rule-out assay for transplantation consideration and/or an intermediate step in surveillance precluding costly imaging on patients with fluctuating AFP results but negative for HCC. | AFP-L3
# Overview
In oncology, AFP-L3 is an isoform of Alpha-fetoprotein (AFP), a substance typically used in the triple test during pregnancy and for screening chronic liver disease patients for hepatocellular carcinoma (HCC). AFP can be fractionated by affinity electrophoresis into 3 glycoforms: L1, L2, and L3 based on the reactivity with the lectin Lens culinaris agglutinin (LCA). AFP-L3 binds strongly to LCA via an additional α 1-6 fucose residue attached at the reducing terminus of N-acetylglucosamine; this is in contrast to the L1 isoform. It is the L1 isoform which is typically associated with non-HCC inflammation of liver disease condition. The L3 isoform is specific to malignant tumors and its detected presence can serve to identify patients whom need increased monitoring for the development of HCC in high risk populations (i.e. chronic hepatitis B & C and/or liver cirrhosis). AFP-L3% is now being considered as a tumor marker for the North American demographic.
# AFP-L3% assay
AFP-L3 is isolated via an immunoassay and quantified using chemiluminesence on an automated platform. Results for AFP-L3 are represented as a ratio of LCA-reactive AFP to total AFP (AFP-L3%). The AFP-L3% assay, a liquid-phase binding assay, will help to identify at-risk subjects earlier, allowing for more intense evaluation for evidence of HCC according to existing practice guidelines in oncology. AFP-L3% is the standard for quantifying the L3 isoform of AFP in serum of high risk chronic liver disease (CLD) patients. Studies have shown that AFP-L3% test results of more than 10% can be indicative of early HCC[citation needed] or early nonseminomatous germ cell tumor.[1]
Early testimonials from hepatologists indicate that there is a target patient population for the AFP-L3% assay. This target population are those CLD patients who have AFP concentrations in the indeterminate range of 20-200+ ng/mL and a small or indeterminate mass on imaging. It is in this range that doctors experience trouble differentiating non-HCC fluctuations in AFP vs indication of HCC. In such patients these hepatologists recommend utilizing AFP-L3% to clarify the disease state. Some hepatologists also use a positive result to urge insurance companies to pay for more frequent and intensive imaging.
Ultimately AFP-L3% may be used as a rule-in or rule-out assay for transplantation consideration and/or an intermediate step in surveillance precluding costly imaging on patients with fluctuating AFP results but negative for HCC. | https://www.wikidoc.org/index.php/AFP-L3 | |
15f911810f3564ad1fa2857bb2b96c9880bb6251 | wikidoc | AGPAT3 | AGPAT3
1-acyl-sn-glycerol-3-phosphate acyltransferase gamma is an enzyme that in humans is encoded by the AGPAT3 gene.
The protein encoded by this gene is an acyltransferase that converts lysophosphatidic acid into phosphatidic acid, which is the second step in the de novo phospholipid biosynthetic pathway. The encoded protein may be an integral membrane protein. Two transcript variants encoding the same protein have been found for this gene.
# Model organisms
Model organisms have been used in the study of AGPAT3 function. A conditional knockout mouse line, called Agpat3tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and one significant abnormality was observed. Few homozygous mutant animals survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these. | AGPAT3
1-acyl-sn-glycerol-3-phosphate acyltransferase gamma is an enzyme that in humans is encoded by the AGPAT3 gene.[1]
The protein encoded by this gene is an acyltransferase that converts lysophosphatidic acid into phosphatidic acid, which is the second step in the de novo phospholipid biosynthetic pathway. The encoded protein may be an integral membrane protein. Two transcript variants encoding the same protein have been found for this gene.[1]
# Model organisms
Model organisms have been used in the study of AGPAT3 function. A conditional knockout mouse line, called Agpat3tm1a(EUCOMM)Wtsi[6][7] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[8][9][10]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[4][11] Twenty five tests were carried out on mutant mice and one significant abnormality was observed.[4] Few homozygous mutant animals survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these.[4] | https://www.wikidoc.org/index.php/AGPAT3 | |
66e01a273ce0df18c28ec05a55d64045d5384e82 | wikidoc | AKAP11 | AKAP11
A-kinase anchor protein 11 is an enzyme that in humans is encoded by the AKAP11 gene.
# Function
The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is expressed at high levels throughout spermatogenesis and in mature sperm. It binds the RI and RII subunits of PKA in testis. It may serve a function in cell cycle control of both somatic cells and germ cells in addition to its putative role in spermatogenesis and sperm function.
# Interactions
AKAP11 has been shown to interact with:
- GSK3B,
- PPP1CA,
- PRKAR2A,
- PRKAR2B.
- VAPB. Binding is via a FFAT motif in the N-terminal portion of AKAP11, similar to that found in AKAP3. | AKAP11
A-kinase anchor protein 11 is an enzyme that in humans is encoded by the AKAP11 gene.[1][2][3]
# Function
The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is expressed at high levels throughout spermatogenesis and in mature sperm. It binds the RI and RII subunits of PKA in testis. It may serve a function in cell cycle control of both somatic cells and germ cells in addition to its putative role in spermatogenesis and sperm function.[3]
# Interactions
AKAP11 has been shown to interact with:
- GSK3B,[4]
- PPP1CA,[4][5]
- PRKAR2A,[2][4][6]
- PRKAR2B.[7]
- VAPB.[8] Binding is via a FFAT motif in the N-terminal portion of AKAP11, similar to that found in AKAP3. [9] | https://www.wikidoc.org/index.php/AKAP11 | |
b5fa3760eb2a15647f1b92b0299a5fa4a5b513ca | wikidoc | AKAP13 | AKAP13
A-kinase anchor protein 13 is an enzyme that in humans is encoded by the AKAP13 gene.
# Function
The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins that have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. Alternative splicing of this gene results in at least 3 transcript variants encoding different isoforms containing a dbl oncogene homology (DH) domain and a pleckstrin homology (PH) domain. The DH domain is associated with guanine nucleotide exchange activation for the Rho/Rac family of small GTP-binding proteins, resulting in the conversion of the inactive GTPase to the active form capable of transducing signals. The PH domain has multiple functions. Therefore, these isoforms function as scaffolding proteins to coordinate a Rho signaling pathway and, in addition, function as protein kinase A-anchoring proteins.
# Interactions
AKAP13 has been shown to interact with Estrogen receptor alpha, CTNNAL1 and PRKAR2A. | AKAP13
A-kinase anchor protein 13 is an enzyme that in humans is encoded by the AKAP13 gene.[1][2][3]
# Function
The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins that have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. Alternative splicing of this gene results in at least 3 transcript variants encoding different isoforms containing a dbl oncogene homology (DH) domain and a pleckstrin homology (PH) domain. The DH domain is associated with guanine nucleotide exchange activation for the Rho/Rac family of small GTP-binding proteins, resulting in the conversion of the inactive GTPase to the active form capable of transducing signals. The PH domain has multiple functions. Therefore, these isoforms function as scaffolding proteins to coordinate a Rho signaling pathway and, in addition, function as protein kinase A-anchoring proteins.[3]
# Interactions
AKAP13 has been shown to interact with Estrogen receptor alpha,[1] CTNNAL1[4] and PRKAR2A.[5][6] | https://www.wikidoc.org/index.php/AKAP13 | |
bc262169c5f7e1ca9c77102170eb7f936b594569 | wikidoc | AKR1B1 | AKR1B1
Aldo-keto reductase family 1, member B1 (AKR1B1), also known as aldose reductase, is an enzyme that in humans is encoded by the AKR1B1 gene. It is a reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent enzyme catalyzing the reduction of various aldehydes and ketones to the corresponding alcohol. The involvement in oxidative stress diseases, cell signal transduction and cell proliferation process endows AKR1B1 the potential as a therapeutic target.
# Structure
## Gene
The AKR1B1 gene lies on the chromosome location of 7q33 and consists of 10 exons. There are a few putative pseudogenes for this gene, and one of them has been confirmed and mapped to chromosome 3.
## Protein
AKR1B1 consists of 316 amino acid residues and weighs 35853Da. It does not possess the traditional dinucleotide binding fold. The way it binds NADPH differs from other nucleotide adenine dinucleotide-dependent enzymes. The active site pocket of human aldose reductase is relatively hydrophobic, lined by seven aromatic and four other non-polar residues.
# Function
AR belongs to the aldehyde-keto reductase superfamily, with a widely expression in human organs including the kidney, lens, retina, nerve, heart, placenta, brain, skeletal muscle, testis, blood vessels, lung, and liver. It is a reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent enzyme catalyzing the reduction of various aldehydes and ketones to the corresponding alcohol. It also participates in glucose metabolism and osmoregulation and plays a protective role against toxic aldehydes derived from lipid peroxidation and steroidogenesis.
# Clinical significance
Under diabetic conditions AR converts glucose into sorbitol, which is then converted to fructose. 20466987 It has been found to play an important role in many diabetes complications such as diabetes retinopathy and renopathy. It is also involved in many oxidative stress diseases, cell signal transduction and cell proliferation process including cardiovascular disorders, sepsis, and cancer.
It has been reported that he action of AR contributes to the activation of retinal microglia, suggesting that inhibition of AR may be of a therapeutic importance to reduce inflammation associated with activation of RMG. Adapting AR inhibitors could as well prevent sepsis complications, prevent angiogenesis, ameliorate mild or asymptomatic diabetic cardiovascular autonomic neuropathy and may be a promising strategy for the treatment of endotoxemia and other ROS-induced inflammatory diseases.
# Interactions
AKR1B1 has been found to interact with:
- ginsenoside 20(S)-Rh2
- alkaloid
- carboxylic acid derivatives
- spirohydantoins
- cyclic amides | AKR1B1
Aldo-keto reductase family 1, member B1 (AKR1B1), also known as aldose reductase, is an enzyme that in humans is encoded by the AKR1B1 gene.[1][2] It is a reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent enzyme catalyzing the reduction of various aldehydes and ketones to the corresponding alcohol. The involvement in oxidative stress diseases, cell signal transduction and cell proliferation process endows AKR1B1 the potential as a therapeutic target.
# Structure
## Gene
The AKR1B1 gene lies on the chromosome location of 7q33 and consists of 10 exons. There are a few putative pseudogenes for this gene, and one of them has been confirmed and mapped to chromosome 3.[2]
## Protein
AKR1B1 consists of 316 amino acid residues and weighs 35853Da. It does not possess the traditional dinucleotide binding fold. The way it binds NADPH differs from other nucleotide adenine dinucleotide-dependent enzymes. The active site pocket of human aldose reductase is relatively hydrophobic, lined by seven aromatic and four other non-polar residues.[3]
# Function
AR belongs to the aldehyde-keto reductase superfamily, with a widely expression in human organs including the kidney, lens, retina, nerve, heart, placenta, brain, skeletal muscle, testis, blood vessels, lung, and liver.[4] It is a reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent enzyme catalyzing the reduction of various aldehydes and ketones to the corresponding alcohol. It also participates in glucose metabolism and osmoregulation and plays a protective role against toxic aldehydes derived from lipid peroxidation and steroidogenesis.[5]
# Clinical significance
Under diabetic conditions AR converts glucose into sorbitol, which is then converted to fructose. 20466987 It has been found to play an important role in many diabetes complications such as diabetes retinopathy and renopathy.[6][7][8] It is also involved in many oxidative stress diseases, cell signal transduction and cell proliferation process including cardiovascular disorders, sepsis, and cancer.[9]
It has been reported that he action of AR contributes to the activation of retinal microglia, suggesting that inhibition of AR may be of a therapeutic importance to reduce inflammation associated with activation of RMG.[10] Adapting AR inhibitors could as well prevent sepsis complications, prevent angiogenesis, ameliorate mild or asymptomatic diabetic cardiovascular autonomic neuropathy and may be a promising strategy for the treatment of endotoxemia and other ROS-induced inflammatory diseases.[8]
# Interactions
AKR1B1 has been found to interact with:
- ginsenoside 20(S)-Rh2 [11]
- alkaloid [12]
- carboxylic acid derivatives[8]
- spirohydantoins[8]
- cyclic amides[8] | https://www.wikidoc.org/index.php/AKR1B1 | |
5b689ee139c469df5c7ae118335e955ce1a86c72 | wikidoc | AKR1C3 | AKR1C3
Aldo-keto reductase family 1 member C3 (AKR1C3), also known as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5, HSD17B5) is a key steroidogenic enzyme that in humans is encoded by the AKR1C3 gene.
# Function
This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14.
# Pathology
AKR1C3 is overexpressed in prostate cancer (PCa) and is associated with the development of castration-resistant prostate cancer (CRPC). In addition, AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression. | AKR1C3
Aldo-keto reductase family 1 member C3 (AKR1C3), also known as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5, HSD17B5) is a key steroidogenic enzyme that in humans is encoded by the AKR1C3 gene.[1][2][3]
# Function
This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14.[3]
# Pathology
AKR1C3 is overexpressed in prostate cancer (PCa) and is associated with the development of castration-resistant prostate cancer (CRPC). In addition, AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression.[4] | https://www.wikidoc.org/index.php/AKR1C3 | |
99f6d21cf9d9abae0459241b1e6e5af786652e72 | wikidoc | ALD-52 | ALD-52
ALD-52 or N-acetyl-LSD, is a chemical analogue of LSD (Lysergic Acid Diethylamide). It was originally discovered by Albert Hofmann but was not widely studied until the rise in popularity of psychedelics in the 1960s.
# Effects
In TiHKAL, Shulgin touches briefly on ALD-52 in entry 26, LSD. His writings are vague, second hand accounts, saying doses in the 50-175µg range have resulted in various conclusions. One found that there was less visual distortion than with LSD and it seems to produce less anxiety and was somewhat less potent than LSD. Another report claimed it was more effective in increasing blood pressure. Yet another could not tell them apart.
It has the same characteristics as LSD, but supposedly "without the anxiety, tenseness, and other problems inherent to it".
# Dangers
In The Hallucinogens by Hoffer and Osmond (1967), ALD-52 (D,L-Acetyllysergic acid diethylamide) is listed as having a lower (approximately 1/5) intravenous toxicity (in rabbits), a lower (approximately 1/8) pyretogenic effect, an equal psychological effect in man, and double the antiserotonin effect as compared with LSD.
# History
It is possible ALD-52 was the active chemical in the "Orange Sunshine" LSD that was widely available in California through 1968 and 1969. The Sonoma County underground chemistry lab of Tim Scully and Nicholas Sand was the source for "Orange Sunshine." It was shut down by the police, and Scully was arrested and prosecuted. This resulted in the first drug analogue trial, where Scully claimed that he and his partners did nothing wrong, because they were producing ALD-52 which was not an illicit drug. However, as the prosecution claimed, there were problems with such a rationale: first, ALD-52 readily undergoes hydrolysis to LSD, and second, the synthesis of ALD-52 required LSD (this was based on the methods available in the scientific literature at the time). Scully was convicted and served time in prison.
# Sources
- Entry #26 from TiHKAL
- everything2
- Totse
- Lycaeum
- White Light | ALD-52
ALD-52 or N-acetyl-LSD, is a chemical analogue of LSD (Lysergic Acid Diethylamide). It was originally discovered by Albert Hofmann but was not widely studied until the rise in popularity of psychedelics in the 1960s.
# Effects
In TiHKAL, Shulgin touches briefly on ALD-52 in entry 26, LSD. His writings are vague, second hand accounts, saying doses in the 50-175µg range have resulted in various conclusions. One found that there was less visual distortion than with LSD and it seems to produce less anxiety and was somewhat less potent than LSD. Another report claimed it was more effective in increasing blood pressure. Yet another could not tell them apart.
It has the same characteristics as LSD, but supposedly "without the anxiety, tenseness, and other problems inherent to it".
# Dangers
In The Hallucinogens by Hoffer and Osmond (1967), ALD-52 (D,L-Acetyllysergic acid diethylamide) is listed as having a lower (approximately 1/5) intravenous toxicity (in rabbits), a lower (approximately 1/8) pyretogenic effect, an equal psychological effect in man, and double the antiserotonin effect as compared with LSD.
# History
It is possible ALD-52 was the active chemical in the "Orange Sunshine" LSD that was widely available in California through 1968 and 1969. The Sonoma County underground chemistry lab of Tim Scully and Nicholas Sand was the source for "Orange Sunshine." It was shut down by the police, and Scully was arrested and prosecuted. This resulted in the first drug analogue trial, where Scully claimed that he and his partners did nothing wrong, because they were producing ALD-52 which was not an illicit drug. However, as the prosecution claimed, there were problems with such a rationale: first, ALD-52 readily undergoes hydrolysis to LSD, and second, the synthesis of ALD-52 required LSD (this was based on the methods available in the scientific literature at the time). Scully was convicted and served time in prison.
# Sources
- Entry #26 from TiHKAL
- everything2
- Totse
- Lycaeum
- White Light
Template:Hallucinogenic lysergamides
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/ALD-52 | |
c8187104301e1cea29005e895ad211cedda501ef | wikidoc | ALOX12 | ALOX12
ALOX12 (EC 1.13.11.31), also known as arachidonate 12-lipoxygenase, 12-lipoxygenase, 12S-Lipoxygenase, 12-LOX, and 12S-LOX is a lipoxygenase-type enzyme that in humans is encoded by the ALOX12 gene which is located along with other lipoyxgenases on chromosome 17p13.3. ALOX12 is 75 kilodalton protein composed of 663 amino acids.
# Nomenclature
Other systematic names for ALOX12 include platelet-type 12-lipoxygenase, arachidonate:oxygen 12-oxidoreductase, Delta12-lipoxygenase, 12Delta-lipoxygenase, C-12 lipoxygenase, leukotriene A4 synthase, and LTA4 synthase. ALOX12, often termed plate platelet-type 12-lipoxygenase, is distinguished from leukocyte-type 12-lipoxygenase which is found in mice, rats, cows, and pigs but not humans. Leukocyte-type 12-lipoxygenase in these animal species shares 73-86% amino acid identity with human ALOX15 but only 57-66% identity with human platelet-type 12-lipoxygenase and, like ALOX15, metabolizes arachidonic acid primarily to 15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (i.e. 15(S)-HpETE; see 15-Hydroxyeicosatetraenoic acid). Accordingly, rodent leukocyte 12-lipoxygenase is deemed an ortholog of ALOX15 and is designated as Alox15.
Human ALOX12 and ALOX15 along with rodent leukocyte-type Alox12 and Alox15 are commonly termed 12/15-lipoxygenases based on their ability to metabolize arachidonic acid to both 12(S)-HpETE and 15(S)-HpETE and to conduct this same metabolism on arachidonic acid that is esterified to membrane phospholipids; human ALOX15B makes 15(S)-HpETE but not 12(S)-HpETE and therefore is not regarded as a 12/15-lipoxygenase. Studies on the role of ALOX12 in pathophysiology using the main models for such functional studies, rats and mice, are complicated because neither species possesses a lipoxygenase that makes a predominance of 12(S)-HETE and therefore is metabolically equivalent to ALOX12. For example, the functions inferred for Alox12 in mice made deficient in Alox12 using knockout methods may not indicate a similar function for ALOX12 in humans due to differences in these two enzymes' metabolic activities. The function of ALOX12 is further clouded by human ALOX15 which metabolizes arachidonic acid primarily to 15(S)-HpETE but also makes lesser but still significant amounts of 12(S)-HpETE (see ALOX15).
ALOX12 is also distinguished from arachidonate 12-lipoxygenase, 12R type (ALOX12B), which metabolizes arachidonic acid to the R stereoisomer of 12(S)-HpETE viz., 12(R)-hydroperoxy-5Z,8Z,10E,14Z-icosatetraenoic acid (12(R)-HpETE), a product with very different pathophysiological roles than that of 12(S)-HpETE (see ALOX12B).
# Discovery
ALOX12, originally called arachidonate 12-lipoxygenase, was first characterized by the Nobel Laureate, Bengt I. Samuelsson, and his famed colleague, Mats Hamberg, in 1974 by showing that human platelets metabolize arachidonic acid not only by the well-known cyclooxygenase pathway into prostaglandins and 12-Hydroxyheptadecatrienoic acid but also by a cyclooxygenase-independent pathway to 12(S)-hydroperoxy-5,8,10,14-eicosatetraenoic acid; this activity was the first mammalian lipoxygenase activity to be characterized. In 1975, the first biological activity was attached to this metabolite in studies showing that it simulated the chemotaxis of human neutrophils. During the several years thereafter, human ALOX12 was purified, characterized biochemically, and had its gene molecularly cloned.
# Tissue distribution
Based predominantly on the presence of its mRNA, human ALOX12 is distributed predominantly in blood platelets and leukocytes and at lower levels in the basal layer of the epidermis (particularly in the skin lesions of psoriasis), islets of Langerhans within the pancreas, and certain cancers.
# Enzyme activities
The control of ALOX12 activity appears to rest principally on the availability of its polyunsaturated fatty acid (PUFA) substrates which are released from storage in membrane phospholipids by cell stimulation. The enzyme participates in arachidonic acid metabolism by conducting the following chemical reaction wherein its substrates are arachidonic acid (also termed as arachidonate or, chemically, as 5Z,8Z,11Z,14Z-eicosatetraenoic acid) and O2 (i.e. oxygen) and its product is 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (i.e. 12S-hydroperoxyeicosatetraenoic acid or 12S-HpETE):
- arachidonate + O2 → 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid
In cells, 12SHpETE may be further metabolized by ALOX12 itself, by ALOXE3 or possibly other, as yet not fully identified, hepoxilin synthases to hepoxilin A3 (8R/S-hydroxy-11,12-oxido-5Z,9E,14Z-eicosatrienoic acid) and B3 (10R/S-hydroxy-11,12-oxido-5Z,8Z,14Z-eicosatrienoic acid):
- 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid → 8R/S-hydroxy-11,12-oxido-5Z,9E,14Z-eicosatrienoic acid + 10R/S-hydroxy-11,12-oxido-5Z,8Z,14Z-eicosatrienoic acid
Hepoxilins can promote certain inflammation responses, increase pain perception (i.e. tactile allodynia), regulate regional blood flow, and contribute to the regulation of blood pressure in animal models (see Hepoxilins). Far more commonly, however, 12S-HpETE is rapidly reduced to its hydroxyl product by ubiquitous cellular peroxidase activities thereby forming 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid, i.e. 12-hydroxyeicosatetraenoic acid or 12S-HETE:
- 12S-hydroperoxy-5(Z),8(Z),10(E),14(Z)-eicosatetraenoic acid → 12S-hydroperoxy-5(Z),8(Z),10(E),14(Z)-eicosatetraenoic acid
12S-HETE promotes inflammation responses, may be involved in the perception of puritis (i.e. itching) in the skin, and regulates regional blood flow in animal models; it also promotes the malignant behavior of cultured human cancer cells as well as the growth of certain cancers in animal models (see 12-HETE). While arachidonate and 12(S)-HETE are the predominant substrates and products, respectively, of ALOX12, the enzyme also metabolizes other PUFA. It metabolizes the omega-3 fatty acid, docosahexaenoic acid (DHA i.e., 4(Z),7(Z),10(Z),13(Z),16(Z),19(Z)-docosahexaenoic acid to 14(R)-hydroperoxy-4(Z),8(Z),10(Z),12(E),16(Z),19(Z)-docosahexaenoic acid)(i.e. 17-hydroperoxy-DHA); then, ALOX12 or an unidentified epoxidase-type enzyme may metabolize this intermediate to an epoxide, 13,14-epoxy-4(Z),7(Z),9(E),11(E),16(Z),19(Z)-docosahexaenoic acid (i.e. 13,14-e-maresin) which metabolized to 7R,14S-dihydroxy-4Z,8E,10E,12Z,16Z,19Z-docosahexaenoic acid (i.e. Maresin 1), by an unidentified epoxide hydrolase-type enzyme:
- DHA → 17-hydroperoxy-DHA → 13,14-e-maresin → Maresin-1
Maresin 1 has a set of activities that may oppose those of 12(S)-HETE and the hepoxilins; it is a member of a class of PUFA metabolites termed Specialized pro-resolution mediators (SPMs) which possess anti-inflammatory, pain-alleviating, and other defensive activities. ALOX12 also acts on leukotriene A4 (LTA4) in a two cellular reaction termed transcellular metabolism: human neutrophils metabolize arachidonic acid to its 5,6-epoxide, LTA4, and releases this intermediate to nearby neutrophils which metabolize it to lipoxin A4 (5S,6R,15S-trihydroxy-7E,9E,11Z,13Z-eicosatetraenoic acid) and lipoxin B4 (5S,14R,15S-trihydroxy-6E,8Z,10E,12E-eicosatetraenoic acid); both lipoxins are SPMs with many SPM-like activities (see lipoxin). ALOX12 may also metabolize lesser amounts of DHA to secondary products including 17-hydroperoxy-DHA, 11-hydroperoxy-DHA, and 8,14-dihydroxy-DHA ALOX12 may likewise metabolize 5(S)-HETE to 5S,12S-dihydroxyeicosatetraenoic acid (12,15-diHETE) and 15S-HETE to 14,15S-diETE. While these compounds have not been thoroughly evaluated for bioactivity, 17-hydroperoxy-HDHA and the reduced product to which it is rapidly converted in cells, 17-hydroxy-HDHA, have been shown to inhibit the growth of cultured human prostate cancer cell by causing them to enter apoptosis.
# Animal studies
Studies on rodents lacking or made deficient in the leukocyte-type 12-lipoxygenase, Alox12 (which is most closely related to human ALOX15) implicate this enzyme in: a) preventing the development and complications of dietary-induced and/or genetically-induced diabetes, adipose cell/tissue dysfunction, and obesity; b) the development of atherosclerosis and Steatohepatitis; b) regulating blood vessel contraction, dilation, pressure, remodeling, and angiogenesis; c) maintaining normal renal, neurological, and brain function; and d) the development of Alzheimer's disease. In these studies, it is usually unclear which, if any metabolite(s) of Alox12 was implicated.
# Preclinical studies
## Metabolic syndrome
The metabolic syndrome is a clustering of at least three of five of the following medical conditions: abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose (or overt diabetes), high serum triglycerides, and low high-density lipoprotein (HDL) levels. ALOX12 and its metabolite, 12(S)-HETE, are elevated in the islets of Langerhans of patients with type 1 diabetes or type 2 diabetes as well as in the fat cells of white adipose tissue of morbidly obese type 2 diabetic patients. The PP cells (i.e. gamma cells) of the pancreas islets appear to be the major if not only site where ALOX12 is expressed in these patients. The studies propose that in the islets of Langerhans ALOX12 and its 12(S)-HETE product cause excessive production of reactive oxygen species and inflammation which lead to losses in insulin-secreting beta cells and thereby types 1 and 2 diabetes and that in adipose tissue the excess in AlOX12, 12(S)-HETE, reactive oxygen species, and inflammation lead to fat cell dysfunction (also see 12-HETE#Inflammation and inflammatory diseases and 12-HETE#Diabetes). Indeed, in one study a Single-nucleotide polymorphism, rs2073438, located in an intron region of the ALOX12 gene was significantly associated with total and percentage fat mass of obese compared to non-obese young Chinese men. ALOX12 and 12(S)-HETE are likewise implicated in essential hypertension (see next section). Hence, ALOX12 and its metabolite(s) may contribute to the development and/or progression of obesity, diabetes, hypertension, and/or the metabolic syndrome.
## Blood vessels
A selective but not totally specific inhibitor of ALOX12 reduced the growth response of cultured human endothelial cells to basic fibroblast growth factor and vascular endothelial growth factor (VEGF); this reduction was partially reversed by 12(S)-HETE; 12(S)-HETE also stimulates human prostate cell lines to produce VEGF. These results suggest that growth responses to the two growth factors involves their stimulation of 12(S)-HETE production by endothelial cells and therefore that ALOX12 may be a target for reducing the neo-vascularization that promotes arthritic and cancer diseases. 12(S)-HETE also dilates human coronary microcirculation arteries by activating these vessels' smooth muscle BKca Potassium channels and is therefore suggested to be an Endothelium-derived hyperpolarizing factor. Finally, a single nucleotide variant in the ALOX12 gene (R261Q ) has been associated with essential hypertension and elevation in the urinary excretion of 12(S)-HETE in humans and may be a contributing factor for to essential hypertension (see also 12-HETE#Blood pressure).
## Alzheimer's disease
Patients with Alzheimer's disease or other forms of dementia have significantly higher levels of 12(S)-HETE (and 15(S)-HETE) in cerebrospinal fluid compared to aged-matched normal individuals. Complementary studies in rodent models bearing human mutated genes for Amyloid precursor protein and/or tau protein (see tau protein#Clinical significance) that produce Alzheimer's dementia-like syndromes implicate 12(S)-HETE, 15(S)-HETE, and a 12/15-lipoxygenase type enzyme in the development and progression of the Alzhiemer's disease-like symptoms and findings in these animals. In a single study, ALOX12 mRNA was found elevated in the brain tissue of Alzheimer disease patients compared to control patients. These results suggest that ALOX12 (or ALOX15) may contribute to the development of Alzheimer's disease in humans.
## Cancer
Studies in prostate cancer find that human prostate cancer cell lines in culture overexpress ALOX12, overproduce 12(S)-HETE, and respond to 12(S)-HETE by increasing their rate of proliferation, increasing their cell surface expression of integrins, increasing their survival and delaying their apoptosis, and increasing their production of vascular endothelial growth factor and MMP9 (i.e. Matrix metallopeptidase 9); selective (but not entirely) specific ALOX12 inhibitors reduced the proliferation and survival of these cells (see also 12-HETE#prostate cancer). These finding suggest that ALOX12 and its 12(S)-HETE product may contribute to the growth and spread of prostate cancer in humans. Recently, hypermethylation of the ALOX12 gene in prostate cancer tissue was associated with clinical predictors for a high rate of recurrent disease. Some studies have found that 12(S)-HETE also promotes the growth and/or related pro-malignant behaviors of various other types of cultured cancer cell lines (see 12-HETE#Other cancers). ALOX12 has been shown to interact with Keratin 5 and LMNA as screened in a yeast two-hybrid interaction library from human epidermoid carcinoma A431 cells; these proteins are candidates for regulating 12-LOX, particularly in tumor cells.
## Platelet function
Although first identified in human platelets, the role of ALOX12 and its major metabolites, 12(S)-HpETE and 12(S)-HETE in platelet function remains controversial and unclear; it is possible that the ALOX12-12(S)-HETE metabolic pathway has dual functions in promoting or inhibiting platelet responses depending on the stimulating agent and response studied but that inhibiting ALOX12 may ultimately prove useful in inhibiting platelet-related blood clotting.
## Other associations
The ALOX12 gene has susceptibility alleles (rs6502997, rs312462, rs6502998, and rs434473) for the parasitic disease, human congenital toxoplasmosis. Fetus bearer of these alleles thus suffer an increased susceptibility to this disease. | ALOX12
ALOX12 (EC 1.13.11.31), also known as arachidonate 12-lipoxygenase, 12-lipoxygenase, 12S-Lipoxygenase, 12-LOX, and 12S-LOX is a lipoxygenase-type enzyme that in humans is encoded by the ALOX12 gene which is located along with other lipoyxgenases on chromosome 17p13.3.[1][2] ALOX12 is 75 kilodalton protein composed of 663 amino acids.
# Nomenclature
Other systematic names for ALOX12 include platelet-type 12-lipoxygenase, arachidonate:oxygen 12-oxidoreductase, Delta12-lipoxygenase, 12Delta-lipoxygenase, C-12 lipoxygenase, leukotriene A4 synthase, and LTA4 synthase. ALOX12, often termed plate platelet-type 12-lipoxygenase, is distinguished from leukocyte-type 12-lipoxygenase which is found in mice, rats, cows, and pigs but not humans. Leukocyte-type 12-lipoxygenase in these animal species shares 73-86% amino acid identity with human ALOX15 but only 57-66% identity with human platelet-type 12-lipoxygenase and, like ALOX15, metabolizes arachidonic acid primarily to 15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (i.e. 15(S)-HpETE; see 15-Hydroxyeicosatetraenoic acid).[3] Accordingly, rodent leukocyte 12-lipoxygenase is deemed an ortholog of ALOX15 and is designated as Alox15.[4]
Human ALOX12 and ALOX15 along with rodent leukocyte-type Alox12 and Alox15 are commonly termed 12/15-lipoxygenases based on their ability to metabolize arachidonic acid to both 12(S)-HpETE and 15(S)-HpETE and to conduct this same metabolism on arachidonic acid that is esterified to membrane phospholipids; human ALOX15B makes 15(S)-HpETE but not 12(S)-HpETE and therefore is not regarded as a 12/15-lipoxygenase.[5] Studies on the role of ALOX12 in pathophysiology using the main models for such functional studies, rats and mice, are complicated because neither species possesses a lipoxygenase that makes a predominance of 12(S)-HETE and therefore is metabolically equivalent to ALOX12.[3][5] For example, the functions inferred for Alox12 in mice made deficient in Alox12 using knockout methods may not indicate a similar function for ALOX12 in humans due to differences in these two enzymes' metabolic activities. The function of ALOX12 is further clouded by human ALOX15 which metabolizes arachidonic acid primarily to 15(S)-HpETE but also makes lesser but still significant amounts of 12(S)-HpETE (see ALOX15).
ALOX12 is also distinguished from arachidonate 12-lipoxygenase, 12R type (ALOX12B), which metabolizes arachidonic acid to the R stereoisomer of 12(S)-HpETE viz., 12(R)-hydroperoxy-5Z,8Z,10E,14Z-icosatetraenoic acid (12(R)-HpETE), a product with very different pathophysiological roles than that of 12(S)-HpETE (see ALOX12B).
# Discovery
ALOX12, originally called arachidonate 12-lipoxygenase, was first characterized by the Nobel Laureate, Bengt I. Samuelsson, and his famed colleague, Mats Hamberg, in 1974 by showing that human platelets metabolize arachidonic acid not only by the well-known cyclooxygenase pathway into prostaglandins and 12-Hydroxyheptadecatrienoic acid but also by a cyclooxygenase-independent pathway to 12(S)-hydroperoxy-5,8,10,14-eicosatetraenoic acid; this activity was the first mammalian lipoxygenase activity to be characterized.[6] In 1975, the first biological activity was attached to this metabolite in studies showing that it simulated the chemotaxis of human neutrophils.[7] During the several years thereafter, human ALOX12 was purified, characterized biochemically, and had its gene molecularly cloned.[3][8]
# Tissue distribution
Based predominantly on the presence of its mRNA, human ALOX12 is distributed predominantly in blood platelets and leukocytes and at lower levels in the basal layer of the epidermis (particularly in the skin lesions of psoriasis), islets of Langerhans within the pancreas, and certain cancers.[9]
# Enzyme activities
The control of ALOX12 activity appears to rest principally on the availability of its polyunsaturated fatty acid (PUFA) substrates which are released from storage in membrane phospholipids by cell stimulation.[10] The enzyme participates in arachidonic acid metabolism by conducting the following chemical reaction wherein its substrates are arachidonic acid (also termed as arachidonate or, chemically, as 5Z,8Z,11Z,14Z-eicosatetraenoic acid) and O2 (i.e. oxygen) and its product is 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (i.e. 12S-hydroperoxyeicosatetraenoic acid or 12S-HpETE):[6][11]
- arachidonate + O2 → 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid
In cells, 12SHpETE may be further metabolized by ALOX12 itself, by ALOXE3 or possibly other, as yet not fully identified, hepoxilin synthases to hepoxilin A3 (8R/S-hydroxy-11,12-oxido-5Z,9E,14Z-eicosatrienoic acid) and B3 (10R/S-hydroxy-11,12-oxido-5Z,8Z,14Z-eicosatrienoic acid):[12][13][14]
- 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid → 8R/S-hydroxy-11,12-oxido-5Z,9E,14Z-eicosatrienoic acid + 10R/S-hydroxy-11,12-oxido-5Z,8Z,14Z-eicosatrienoic acid
Hepoxilins can promote certain inflammation responses, increase pain perception (i.e. tactile allodynia), regulate regional blood flow, and contribute to the regulation of blood pressure in animal models (see Hepoxilins). Far more commonly, however, 12S-HpETE is rapidly reduced to its hydroxyl product by ubiquitous cellular peroxidase activities thereby forming 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid, i.e. 12-hydroxyeicosatetraenoic acid or 12S-HETE:[15]
- 12S-hydroperoxy-5(Z),8(Z),10(E),14(Z)-eicosatetraenoic acid → 12S-hydroperoxy-5(Z),8(Z),10(E),14(Z)-eicosatetraenoic acid
12S-HETE promotes inflammation responses, may be involved in the perception of puritis (i.e. itching) in the skin, and regulates regional blood flow in animal models; it also promotes the malignant behavior of cultured human cancer cells as well as the growth of certain cancers in animal models (see 12-HETE). While arachidonate and 12(S)-HETE are the predominant substrates and products, respectively, of ALOX12, the enzyme also metabolizes other PUFA. It metabolizes the omega-3 fatty acid, docosahexaenoic acid (DHA i.e., 4(Z),7(Z),10(Z),13(Z),16(Z),19(Z)-docosahexaenoic acid to 14(R)-hydroperoxy-4(Z),8(Z),10(Z),12(E),16(Z),19(Z)-docosahexaenoic acid)(i.e. 17-hydroperoxy-DHA); then, ALOX12 or an unidentified epoxidase-type enzyme may metabolize this intermediate to an epoxide, 13,14-epoxy-4(Z),7(Z),9(E),11(E),16(Z),19(Z)-docosahexaenoic acid (i.e. 13,14-e-maresin) which metabolized to 7R,14S-dihydroxy-4Z,8E,10E,12Z,16Z,19Z-docosahexaenoic acid (i.e. Maresin 1), by an unidentified epoxide hydrolase-type enzyme:
- DHA → 17-hydroperoxy-DHA → 13,14-e-maresin → Maresin-1
Maresin 1 has a set of activities that may oppose those of 12(S)-HETE and the hepoxilins; it is a member of a class of PUFA metabolites termed Specialized pro-resolution mediators (SPMs) which possess anti-inflammatory, pain-alleviating, and other defensive activities.[16] ALOX12 also acts on leukotriene A4 (LTA4) in a two cellular reaction termed transcellular metabolism: human neutrophils metabolize arachidonic acid to its 5,6-epoxide, LTA4, and releases this intermediate to nearby neutrophils which metabolize it to lipoxin A4 (5S,6R,15S-trihydroxy-7E,9E,11Z,13Z-eicosatetraenoic acid) and lipoxin B4 (5S,14R,15S-trihydroxy-6E,8Z,10E,12E-eicosatetraenoic acid); both lipoxins are SPMs with many SPM-like activities (see lipoxin).[17] ALOX12 may also metabolize lesser amounts of DHA to secondary products including 17-hydroperoxy-DHA, 11-hydroperoxy-DHA, and 8,14-dihydroxy-DHA[16] ALOX12 may likewise metabolize 5(S)-HETE to 5S,12S-dihydroxyeicosatetraenoic acid (12,15-diHETE) and 15S-HETE to 14,15S-diETE.[10] While these compounds have not been thoroughly evaluated for bioactivity, 17-hydroperoxy-HDHA and the reduced product to which it is rapidly converted in cells, 17-hydroxy-HDHA, have been shown to inhibit the growth of cultured human prostate cancer cell by causing them to enter apoptosis.[18]
# Animal studies
Studies on rodents lacking or made deficient in the leukocyte-type 12-lipoxygenase, Alox12 (which is most closely related to human ALOX15) implicate this enzyme in: a) preventing the development and complications of dietary-induced and/or genetically-induced diabetes, adipose cell/tissue dysfunction, and obesity; b) the development of atherosclerosis and Steatohepatitis; b) regulating blood vessel contraction, dilation, pressure, remodeling, and angiogenesis; c) maintaining normal renal, neurological, and brain function; and d) the development of Alzheimer's disease.[4][5][19] In these studies, it is usually unclear which, if any metabolite(s) of Alox12 was implicated.
# Preclinical studies
## Metabolic syndrome
The metabolic syndrome is a clustering of at least three of five of the following medical conditions: abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose (or overt diabetes), high serum triglycerides, and low high-density lipoprotein (HDL) levels. ALOX12 and its metabolite, 12(S)-HETE, are elevated in the islets of Langerhans of patients with type 1 diabetes or type 2 diabetes as well as in the fat cells of white adipose tissue of morbidly obese type 2 diabetic patients.[4] The PP cells (i.e. gamma cells) of the pancreas islets appear to be the major if not only site where ALOX12 is expressed in these patients.[4] The studies propose that in the islets of Langerhans ALOX12 and its 12(S)-HETE product cause excessive production of reactive oxygen species and inflammation which lead to losses in insulin-secreting beta cells and thereby types 1 and 2 diabetes and that in adipose tissue the excess in AlOX12, 12(S)-HETE, reactive oxygen species, and inflammation lead to fat cell dysfunction (also see 12-HETE#Inflammation and inflammatory diseases and 12-HETE#Diabetes). Indeed, in one study a Single-nucleotide polymorphism, rs2073438,[20] located in an intron region of the ALOX12 gene was significantly associated with total and percentage fat mass of obese compared to non-obese young Chinese men.[4][9][14] ALOX12 and 12(S)-HETE are likewise implicated in essential hypertension (see next section). Hence, ALOX12 and its metabolite(s) may contribute to the development and/or progression of obesity, diabetes, hypertension, and/or the metabolic syndrome.
## Blood vessels
A selective but not totally specific inhibitor of ALOX12 reduced the growth response of cultured human endothelial cells to basic fibroblast growth factor and vascular endothelial growth factor (VEGF); this reduction was partially reversed by 12(S)-HETE; 12(S)-HETE also stimulates human prostate cell lines to produce VEGF.[15] These results suggest that growth responses to the two growth factors involves their stimulation of 12(S)-HETE production by endothelial cells and therefore that ALOX12 may be a target for reducing the neo-vascularization that promotes arthritic and cancer diseases. 12(S)-HETE also dilates human coronary microcirculation arteries by activating these vessels' smooth muscle BKca Potassium channels and is therefore suggested to be an Endothelium-derived hyperpolarizing factor.[5][15] Finally, a single nucleotide variant in the ALOX12 gene (R261Q [3957 G>A]) has been associated with essential hypertension and elevation in the urinary excretion of 12(S)-HETE in humans and may be a contributing factor for to essential hypertension (see also 12-HETE#Blood pressure).[5][21]
## Alzheimer's disease
Patients with Alzheimer's disease or other forms of dementia have significantly higher levels of 12(S)-HETE (and 15(S)-HETE) in cerebrospinal fluid compared to aged-matched normal individuals. Complementary studies in rodent models bearing human mutated genes for Amyloid precursor protein and/or tau protein (see tau protein#Clinical significance) that produce Alzheimer's dementia-like syndromes implicate 12(S)-HETE, 15(S)-HETE, and a 12/15-lipoxygenase type enzyme in the development and progression of the Alzhiemer's disease-like symptoms and findings in these animals.[19] In a single study, ALOX12 mRNA was found elevated in the brain tissue of Alzheimer disease patients compared to control patients.[9] These results suggest that ALOX12 (or ALOX15) may contribute to the development of Alzheimer's disease in humans.
## Cancer
Studies in prostate cancer find that human prostate cancer cell lines in culture overexpress ALOX12, overproduce 12(S)-HETE, and respond to 12(S)-HETE by increasing their rate of proliferation, increasing their cell surface expression of integrins, increasing their survival and delaying their apoptosis, and increasing their production of vascular endothelial growth factor and MMP9 (i.e. Matrix metallopeptidase 9); selective (but not entirely) specific ALOX12 inhibitors reduced the proliferation and survival of these cells (see also 12-HETE#prostate cancer). These finding suggest that ALOX12 and its 12(S)-HETE product may contribute to the growth and spread of prostate cancer in humans.[15] Recently, hypermethylation of the ALOX12 gene in prostate cancer tissue was associated with clinical predictors for a high rate of recurrent disease.[22] Some studies have found that 12(S)-HETE also promotes the growth and/or related pro-malignant behaviors of various other types of cultured cancer cell lines (see 12-HETE#Other cancers).[15] ALOX12 has been shown to interact with Keratin 5 and LMNA as screened in a yeast two-hybrid interaction library from human epidermoid carcinoma A431 cells; these proteins are candidates for regulating 12-LOX, particularly in tumor cells.[23]
## Platelet function
Although first identified in human platelets, the role of ALOX12 and its major metabolites, 12(S)-HpETE and 12(S)-HETE in platelet function remains controversial and unclear; it is possible that the ALOX12-12(S)-HETE metabolic pathway has dual functions in promoting or inhibiting platelet responses depending on the stimulating agent and response studied but that inhibiting ALOX12 may ultimately prove useful in inhibiting platelet-related blood clotting.[15]
## Other associations
The ALOX12 gene has susceptibility alleles (rs6502997,[24] rs312462,[25] rs6502998,[26] and rs434473[27]) for the parasitic disease, human congenital toxoplasmosis.[9][28] Fetus bearer of these alleles thus suffer an increased susceptibility to this disease. | https://www.wikidoc.org/index.php/ALOX12 | |
f0d3a6823c608761bc9a018c4e0414dd3362e649 | wikidoc | ALOX15 | ALOX15
ALOX15 (also termed arachidonate 15-lipoxygenase, 15-lipoxygenase-1, 15-LO-1, 15-LOX-1) is, like other lipoxygenases, a seminal enzyme in the metabolism of polyunsaturated fatty acids to a wide range of physiologically and pathologically important products.
▼ Gene Function
Kelavkar and Badr (1999) stated that the ALOX15 gene product is implicated in antiinflammation, membrane remodeling, and cancer development/metastasis. Kelavkar and Badr (1999) described experiments yielding data that supported the hypothesis that loss of the TP53 gene, or gain-of-function activities resulting from the expression of its mutant forms, regulates ALOX15 promoter activity in human and in mouse, albeit in directionally opposite manners. These studies defined a direct link between ALOX15 gene activity and an established tumor-suppressor gene located in close chromosomal proximity. Kelavkar and Badr (1999) referred to this as evidence that 15-lipoxygenase is a mutator gene.
▼ Mapping
By PCR analysis of a human-hamster somatic hybrid DNA panel, Funk et al. (1992) demonstrated that genes for 12-lipoxygenase and 15-lipoxygenase are located on human chromosome 17, whereas the most unrelated lipoxygenase (5-lipoxygenase) was mapped to chromosome 10.
Kelavkar and Badr (1999) stated that the ALOX15 gene maps to 17p13.3 in close proximity to the tumor-suppressor gene TP53 (191170). In humans, it is encoded by the ALOX15 gene located on chromosome 17p13.3. This 11 kilobase pair gene consists of 14 exons and 13 introns coding for a 75 kiloDalton protein composed of 662 amino acids. 15-LO is to be distinguished from another human 15-lipoxygenase enzyme, ALOX15B (also termed 15-lipoxygenase-2). Orthologs of ALOX15, termed Alox15, are widely distributed in animal and plant species but commonly have different enzyme activities and make somewhat different products than ALOX15.
# Nomenclature
Human ALOX15 was initially named arachidonate 15-lipoxygenase or 15-lipoxygenase but subsequent studies uncovered a second human enzyme with 15-lipoxygenase activity as well as various non-human mammalian Alox15 enzymes that are closely related to and therefore orthologs of human ALOX15. Many of the latter Alox15 enzymes nonetheless possess predominantly or exclusively 12-lipoxygenase rather than 15-lipoxygenase activity. Consequently, human ALOX15 is now referred to as arachidonate-15-lipoxygenase-1, 15-lipoxygenase-1, 15-LOX-1, 15-LO-1, human 12/15-lipoxygenase, leukocyte-type arachidonate 12-lipoxygenase, or arachidonate omega-6 lipoxygenase. The second discovered human 15-lipoxygenase, a product of the ALOX15B gene, is termed ALOX15B, arachidonate 15-lipoxygenase 2, 15-lipoxygenase-2, 15-LOX-2, 15-LO-2, arachidonate 15-lipoxygenase type II, arachidonate 15-lipoxygenase, second type, and arachidonate 15-lipoxygenase; and mouse, rat, and rabbit rodent orthologs of human ALOX15, which share 74-81% amino acid identity with the human enzyme, are commonly termed Alox15, 12/15-lipoxygenase, 12/15-LOX, or 12/15-LO).
Both human ALOX15 and ALOX15B genes are located on chromosome 17; their product proteins have an amino acid sequence identity of only ~38%; they also differ in the polyunsaturated fatty acids that they prefer as substrates and exhibit different product profiles when acting on the same substrates.
# Tissue distribution
Human ALOX15 protein is highly expressed in circulating blood eosinophils and reticulocytes, cells, bronchial airway epithelial cells, mammary epithelial cells, the Reed-Sternberg cells of Hodgkin's lymphoma, corneal epithelial cells, and dendritic cells; it is less strongly expressed in alveolar macrophages, tissue mast cells, tissue fibroblasts, circulating blood neutrophils, vascular endothelial cells, joint Synovial membrane cells, seminal fluid, prostate epithelium cells, and mammary ductal epithelial cells.
The distribution of Alox15 in sub-human primates and, in particular, rodents differs significantly from that of human ALOX15; this, along with their different principal product formation (e.g. 12-HETE rather than 15-HETE) has made the findings of Alox15 functions in rat, mouse, or rabbit models difficult to extrapolate to the function of ALOX15 in humans.
# Enzyme activities
## Lipoxygenase activity
ALOX15 and Alox15 enzymes are non-heme, iron-containing dioxygenases. They commonly catalyze the attachment of molecular oxygen O2 as a peroxy residue to polyunsaturated fatty acids (PUFA) that contain two carbon-carbon double bonds that for the human ALOX15 are located between carbons 10 and 9 and 7 and 6 as numbered counting backward from the last or omega (i.e. ω) carbon at the methyl end of the PUFA (these carbons are also termed ω-10 and ω-9 and ω-7 and ω-6). In PUFAs that do not have a third carbon-carbon double bound between their ω-13 and ω-12 carbons, human ALOX15 forms ω-6 peroxy intermediates; in PUFAs that do have this third double bound, human ALOX15 makes the ω-6 peroxy intermediate but also small amounts of the ω-9 peroxy intermediate. Rodent Alox15 enzymes, in contrast, produce almost exclusively ω-9 peroxy intermediates. Concurrently, ALOX15 and rodent Alox15 enzymes rearrange the carbon-carbon double bonds to bring them into the 1S-hydroxy-2E,4Z-diene configuration. ALOX15 and Alox15 enzymes act with a high degree of Stereospecificity to form products that position the hydroperoxy residue in the S stereoisomer configuration.
## Lipohydroperoxidase activity
Human ALOX15 can also convert the peroxy PUFA intermediate to a cyclic ether with a three-atom ring, i.e. an epoxide intermediate that is attacked by a water molecule to form epoxy-hydrpoxy PUFA products. Eoxins stimulate vascular permeability in an ex vivo human vascular endothelial model system.
## Leukotriene synthase activity
The PUFA epoxide of arachidonic acid made by ALOX15 may also be conjugated with glutathione to form eoxin A4 which product can be further metabolized to eoxin B4, eoxin C4, and eoxin D4.
# Substrates, substrate metabolites, and metabolite activities
Among their physiological substrates, human and rodent AlOX15 enzymes act on linoleic acid, alpha-linolenic acid, gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid when presented not only as free acids but also when incorporated as esters in phospholipids, glycerides, or Cholesteryl esters. The human enzyme is particularly active on linoleic acid, preferring it over arachidonic acid. It is less active on PUFA that are esters within the cited lipids.
## Arachidonic acid
Arachidonic acid (AA) has double bonds between carbons 5-6, 8-9, 11-12, and 14-15; these double bonds are in the cis (see Cis–trans isomerism or Z as opposed to the trans or E configuration. ALOX15 adds a hydroperoxy residue to AA at carbons 15 and to a lesser extent 12 to form 15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15(S)-HpETE) and 12(S)-hydroperoxy-5Z,8Z,10E, 15S-eicosatetraenoic acid (12(S)-HpETE); the purified enzyme makes 15(S)-HpETE and 12(S)-HpETE in a product ratio of ~4-9 to 1. Both products may be rapidly reduced by ubiquitous cellular Glutathione peroxidase enzymes to their corresponding hydroxy analogs, 15(S)-HETE (see 15-hydroxyeicosatetraenoic acid) and 12(S)-HETE (see 12-Hydroxyeicosatetraenoic acid). 15(S)-HpETE and 15(S)-HETE bind to and activate the Leukotriene B4 receptor 2, activate the Peroxisome proliferator-activated receptor gamma, and at high concentrations cause cells to generate toxic reactive oxygen species; one or more of these effects may be at least in part responsible for their ability to promote inflammatory responses, alter the growth of various times of human cancer cell lines, contract various types of blood vessels, and stimulate pathological fibrosis in pulmonary arteries and liver (see 15-Hydroxyicosatetraenoic acid#15(S)-HpETE and 15(S)-HETE). 15(S)-HpETE and 15(S)-HETE are esterified into membrane phospholipids where they may be stored and subsequently released during cell stimulation. As one aspect of this processing, the two products are progressively esterified in mitochondria membrane phospholipids during the maturation of red blood cells (see erythropoiesis) and thereby may serve to signal for the degradation of the mitochondria and the maturation of these precursors to red blood cells in mice. This pathway operates along with two other mitochondria-removing pathways and therefore does not appear essential for mouse red blood cell maturation.
15-(S)-HpETE and 15(S)-HETE may be further metabolized to various bioactive products including:
- lipoxin (LX)A4, LXB4, AT-LXA4, and AT-LXB4; these metabolites are members of the specialized proresolving mediator class of anti-inflammatory agents that contribute to the resolution of inflammatory responses and inflammation-based diseases in animal models and, potentially, humans (see specialized proresolving mediators and lipoxins).
- Hepoxilin isomers (e.g. 1S-hydroxy-14S,15S-epoxy-5Z,8Z,12E-eicosatrienoic acid and 13R-hydroxy-14S,15S-epoxy-5Z,8Z,11Z-eicosatrienoic acid ) which may contribute to the regulation of inflammation responses and insulin secretion (see hepoxilins).
- Eoxins (e.g. eoxin C4, 14,15-eoxin D4, and eoxin E4) which have pro-inflammatory actions and contribute to severe asthma, aspirin-induced asthma attacks, and other allergy reactions; they may also be involved in the pathology of Hodgkins disease (see Eoxins).
- 8(S),15(S)-dihydroxy-5Z,9E,llZ,13E-eicosatetraenoic acid (8(S),15(S)-diHETE), an inhibitor of human platelet aggregation (see Dihydroxy-E,Z,E-PUFA).
- 5(S),15(S)-dihydroxy-6Z,8E,llE,13Z-eicosatetraenoic acid (5S),15(S)-diHETE) and its 5-ketone analog, 5-oxo-15(S)-hydroxy-ETE. These are weak and potent, respectively, stimulators of human eosinophil, neutrophil, and monocyte chemotaxis and thereby possible contributors to human allergic and non-allergic inflammation responses (see 5-Hydroxyicosatetraenoic acid#Inflammation and 5-Hydroxyicosatetraenoic acid#Allergy).
- 15-Oxo-ETE which inhibits the growth of cultured Human umbilical vein endothelial cells and various human cancer cell lines; it is also has activities on THP1 cell line cells suggesting that it might act as an inhibitor of inflammatory and oxidative stress reactions (see15-Hydroxyicosatetraenoic acid#15-oxo-ETE).
The minor products of ALOX15, 12-(S)-HpETE and 12(S)-HETE, possess a broad range of activities. One or both of these compounds stimulates cells by binding with and activating two G protein-coupled receptors, GPR31 and the Leukotriene B4 receptor 2; 12S-HETE also acts as a receptor antagonist by binding to but not stimulating the Thromboxane receptor thereby inhibiting the actions of Thromboxane A2 and Prostaglandin H2 (see 12-Hydroxyeicosatetraenoic acid#Receptor targets and mechanisms of action). As at least a partial consequence of these receptor-directed actions, one or both the two ALOX15 products exhibit pro-inflammation, diabetes-inducing, and vasodilation activities in animal models; cancer-promoting activity on cultured human cancer cells; and other actions (see 12-Hydroxyeicosatetraenoic acid#Activities and possible clinical significance). The two products are also further metabolized to various bioactive products including:
- Hepoxilin A3 and Hepoxilin B3 along with their respective tri-hydroxyl metabolites, trioxilin A3 and trioxilin B3. These metabolites have been reported to have anti-inflammatory activity, to have vasodilationactivity, to promote pain perceptrion, to reverse oxidative stress in cells, and to promote insulin secretion in animal model systems (see Hepoxilin.
- 12-Oxo-ETE, which along with 12S-HETE, activates the Leukotriene B4 receptor, Leukotriene B4 receptor 2 (BLT2) but not its Leukotriene B4 receptor 1 (BLT1). This allows the possibility that 12-oxo-ETE contributes to the pro-inflammatory and other activities that BLT2 regulates (see 12-HETE#Inflammation and inflammatory diseases and Leukotriene B4 receptor 2.
## Docosahexaenoic acid
Human ALOX15 metabolizes docosahexaenoic acid (DHA) to 17S-Hydroperoxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid (17S-HpDHA) and 17S-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid (17S-HDHA). One or both of these products stimulate human breast and prostate cell lines to proliferate in culture and 17S-HDHA possesses potent specialized proresolving mediator activity (see specialized proresolving mediators#DHA-derived Resolvins). One or both of these products may be further metabolized enzymatically to:
- Resolvin Ds (RvDs), i.e. RvD-1, RvD2, RvD3, RvD4, RvD5, and RvD6 (see resolvin and specialized proresolving mediators#DHA-derived Resolvins) and protectin Ds (PDs), i.e. PD1, PDX, 20-hydroxy-PD1, 17-epi-PD1, and 10-epi-PD1 (see neuroprotectin D1 and specialized proresolving mediators#DHA-derived protectins/neuroprotectins). These products are members of, and have a wide range of activities common to, the specialized proresolving mediators class of metabolites.
## Eicosapentaenoic acid
Human ALOX15 metabolizes eicosapentaenoic acid to 15S-hydroperoxy-5Z,8Z,11Z,13E,17E-eicosapentaenoic acid (15S-HpEPA) and 15S-hydroxy-5Z,8Z,11Z,13E,17E-eicosapentaenoic acid (15S-HEPA); 15S-HEPA inhibits ALOX5-dependent production of the pro-inflammatory mediator, LTB4, in cells, and may thereby serve an anti-inflammatory function. These products may be further metabolized to:
- Resolvin E3, a specialized proresolvin mediator with anti-inflammatory activity (see Specialized proresolving mediators#EPA-derived resolvins (i.e. RvE)).
## n-3 Docosaexaenoic acid
Human cells and mouse tissues metabolize n-3 docosapentaenoic acid (i.e., 7Z,10Z,13Z,16Z,19Z-docosapentaenoic acid, see clupanodonic acid) to a series of products that have been classified as specialized proresolvin mediators. Base on the analogy to docosahexaenoic acid metabolism to resolving D's, it is presumed that a 15-lipoxygenase, most likely ALOX15 in humans, contributes to this metabolism. These products, termed n-3 Resolven D's (RvDn-3's), are:
- RvD1n-3, RvD2n-3, and RvD3n-3; each of these products possesses potent anti-inflammatory activity (see Specialized proresolving mediators#n-3 DPA-derived resolvins).
## Linoleic acid
Human 15-LOX-1 prefers linoleic acid over arachidonic acid as its primary substrate, oxygenating it at carbon 13 to form 13(S)-hydroperoxy-9Z,11E-octadecaenoic acid (13-HpODE or 13(S)-HpODE) which may then be reduce to the corresponding hydroxy derivative, 13(S)-HODE or 13-HODE (see 13-Hydroxyoctadecadienoic acid). In addition to 13(S)-HpODE, non-human 15-LOX1 orthologs such as mouse 12/15-LOX and soybean 15-LOX metabolize linoleic acid to 9-hydroperoxy-10E, 12Z-octadecaenoic acid (9-HpODE or 9(S)-HpODE), which is rapidly converted to 9(S)-HODE (9-HODE) (see 9-Hydroxyoctadecadienoic acid)). 13(S)-HODE acts through Peroxisome proliferator-activated receptors and the TRPV1 and human GPR132 receptors to stimulate a variety of responses related to monocyte maturation, lipid metabolism, and neuron activation (see 13-Hydroxyoctadecadienoic acid##Activities of 13-HODEs; 9(S)-HODE is a marker for diseases involving oxidative stress and may contribute to this disease as well as to pain perception and atherosclerosis (see 9-Hydroxyoctadecadienoic acid##Biological and clinical relevancy of 9-HODEs). The two HODEs can be further metabolized to their ketones, 13-oxo-9Z,11E-octadecaenoic acid and 9-oxo-10E, 12Z-octadecaenoic acid; these ketones have been implicated as biomarkers for and possible contributors to the inflammatory component of atherosclerosis, Alzheimer's disease, Steatohepatitis, and other pathological conditions.
## Dihomo-γ-linolenic acid
Human neutrophils, presumably using their ALOX 15, metabolize Dihomo-γ-linolenic acid (8Z,11Z,14Z-eicosatrienoic acid) to 15S-hydroperoxy-8Z,11Z,13E-eicosatrienoic acid and 15S-hydroxy-8Z,11Z,13E-eicosatrienoic acid (15S-HETrE). 15S-HETrE possesses anti-inflammatory activity.
# Gene manipulation studies
Mice made deficient in their 12/15-lipoxygenase gene (Alox15) exhibit a prolonged inflammatory response along with various other aspects of a pathologically enhanced inflammatory response in experimental models of cornea injury, airway inflammation, and peritonitis. These mice also show an accelerated rate of progression of atherosclerosis whereas mice made to overexpress 12/15-lipoxygenase exhibit a delayed rate of atherosclerosis development. Alox15 overexpressing rabbits exhibited reduced tissue destruction and bone loss in a model of periodontitis. Finally, Control mice, but not 12/15-lipoxygense deficient mice responded to eicospentaenoic acid administration by decreasing the number of lesions in a model of endometriosis. These studies indicate that the suppression of inflammation is a major function of 12/15-lipoxygenase and the Specialized proresolving mediators it produces in rodents; although rodent 12/15-lipoxygenase differs from human ALOX15 in the profile of the PUFA metabolites that it produces as well as various other parameters (e.g. tissue distribution), these genetic studies allow that human ALOX15 and the specialized proresolving mediators it produces may play a similar major anti-inflammatory function in humans.
# Clinical significance
## Inflammatory diseases
À huge and growing number of studies in animal models suggest that 15-LOX-1 and its lipoxin, resolvin, and protectin metabolites (see Specialized proresolving mediators) to inhibit, limit, and resolve diverse inflammatory diseases including periodontitis, peritonitis, sepsis, and other pathogen-induced inflammatory responses; in eczema, arthritis, asthma, cystic fibrosis, atherosclerosis, and adipose tissue inflammation; in the insulin resistance that occurs in obesity that is associated with diabetes and the metabolic syndrome; and in Alzheimer's disease. While these studies have not yet been shown to translate to human diseases, first and second generation synthetic resolvins and lipoxins, which unlike their natural analogs, are relatively resistant to metabolic inactivation, have been made and tested as inflammation inhibitors in animal models. These synthetic analogs may prove to be clinically useful for treating the cited human inflammatory diseases.
By metabolizing the ω-3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid, into 17-HpDHA, 17-HDHA, and the resolvins and protectins, 15-LOX-1's metabolic action is thought to be one mechanism by which dietary ω-3 polyunsaturated fatty acids, particularly fish oil, act to ameliorate inflammation, inflammation-related diseases, and certain cancers.
## Asthma
15-LOX-1 and its 5-oxo-15-hydroxy-ETE and eoxin metabolites have been suggested as potential contributors to, and therefore targets for the future study and treatment of, human allergen-induced asthma, aspirin-induced asthma, and perhaps other allergic diseases.
## Cancer
In colorectal, breast, and kidney cancers, 15-LOX-1 levels are low or absent compared to the cancers' normal tissue counterparts and/or these levels sharply decline as the cancers progress. These results, as well as a 15-LOX-1 transgene study on colon cancer in mice suggests but do not prove that 15-LOX-1 is a tumor suppressor.
By metabolizing ω-3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid, into lipoxins and resolvins, 15-LOX-1 is thought to be one mechanism by which dietary ω-3 polyunsaturated fatty acids, particularly fish oil, may act to reduce the incidence and/or progression of certain cancers. Indeed, the ability of docosahexaenoic acid to inhibit the growth of cultured human prostate cancer cells is totally dependent upon the expression of 15-LOX-1 by these cells and appears due to this enzyme's production of docosahexaenoic acid metabolites such as 17(S)-HpETE, 17(S)-HETE, and/or and, possibly, an isomer of protectin DX (10S, 17S-dihydroxy-4Z, 7Z, 11E, 13Z, 15E, 19Z-docosahexaenoic acid)
Kelavkar et.al have shown that aberrant overexpression of 15-LO-1 occurs in human PCa, particularly high-grade PCa, and in high-grade prostatic intraepithelial neoplasia (HGPIN), and that the murine orthologue is increased in SV40-based genetically engineered mouse (GEM) models of PCa, such as LADY and TRansgenic Adenocarcinoma of Mouse Prostate.Targeted overexpression of h15-LO-1 (a gene overexpressed in human PCa and HGPIN) to mouse prostate is sufficient to promote epithelial proliferation and mPIN development. These results support 15-LO-1 as having a role in prostate tumor initiation and as an early target for dietary or other prevention strategies. The FLiMP mouse model should also be useful in crosses with other GEM models to further define the combinations of molecular alterations necessary for PCa progression. | ALOX15
ALOX15 (also termed arachidonate 15-lipoxygenase, 15-lipoxygenase-1, 15-LO-1, 15-LOX-1) is, like other lipoxygenases, a seminal enzyme in the metabolism of polyunsaturated fatty acids to a wide range of physiologically and pathologically important products.
▼ Gene Function
Kelavkar and Badr (1999) stated that the ALOX15 gene product is implicated in antiinflammation, membrane remodeling, and cancer development/metastasis. Kelavkar and Badr (1999) described experiments yielding data that supported the hypothesis that loss of the TP53 gene, or gain-of-function activities resulting from the expression of its mutant forms, regulates ALOX15 promoter activity in human and in mouse, albeit in directionally opposite manners. These studies defined a direct link between ALOX15 gene activity and an established tumor-suppressor gene located in close chromosomal proximity. Kelavkar and Badr (1999) referred to this as evidence that 15-lipoxygenase is a mutator gene.
▼ Mapping
By PCR analysis of a human-hamster somatic hybrid DNA panel, Funk et al. (1992) demonstrated that genes for 12-lipoxygenase and 15-lipoxygenase are located on human chromosome 17, whereas the most unrelated lipoxygenase (5-lipoxygenase) was mapped to chromosome 10.
Kelavkar and Badr (1999) stated that the ALOX15 gene maps to 17p13.3 in close proximity to the tumor-suppressor gene TP53 (191170). In humans, it is encoded by the ALOX15 gene located on chromosome 17p13.3.[1] This 11 kilobase pair gene consists of 14 exons and 13 introns coding for a 75 kiloDalton protein composed of 662 amino acids. 15-LO is to be distinguished from another human 15-lipoxygenase enzyme, ALOX15B (also termed 15-lipoxygenase-2).[2] Orthologs of ALOX15, termed Alox15, are widely distributed in animal and plant species but commonly have different enzyme activities and make somewhat different products than ALOX15.
# Nomenclature
Human ALOX15 was initially named arachidonate 15-lipoxygenase or 15-lipoxygenase but subsequent studies uncovered a second human enzyme with 15-lipoxygenase activity as well as various non-human mammalian Alox15 enzymes that are closely related to and therefore orthologs of human ALOX15. Many of the latter Alox15 enzymes nonetheless possess predominantly or exclusively 12-lipoxygenase rather than 15-lipoxygenase activity. Consequently, human ALOX15 is now referred to as arachidonate-15-lipoxygenase-1, 15-lipoxygenase-1, 15-LOX-1, 15-LO-1, human 12/15-lipoxygenase, leukocyte-type arachidonate 12-lipoxygenase, or arachidonate omega-6 lipoxygenase. The second discovered human 15-lipoxygenase, a product of the ALOX15B gene, is termed ALOX15B, arachidonate 15-lipoxygenase 2, 15-lipoxygenase-2, 15-LOX-2, 15-LO-2, arachidonate 15-lipoxygenase type II, arachidonate 15-lipoxygenase, second type, and arachidonate 15-lipoxygenase; and mouse, rat, and rabbit rodent orthologs of human ALOX15, which share 74-81% amino acid identity with the human enzyme, are commonly termed Alox15, 12/15-lipoxygenase, 12/15-LOX, or 12/15-LO).[1][2]
Both human ALOX15 and ALOX15B genes are located on chromosome 17; their product proteins have an amino acid sequence identity of only ~38%; they also differ in the polyunsaturated fatty acids that they prefer as substrates and exhibit different product profiles when acting on the same substrates.[2][3]
# Tissue distribution
Human ALOX15 protein is highly expressed in circulating blood eosinophils and reticulocytes, cells, bronchial airway epithelial cells, mammary epithelial cells, the Reed-Sternberg cells of Hodgkin's lymphoma, corneal epithelial cells, and dendritic cells; it is less strongly expressed in alveolar macrophages, tissue mast cells, tissue fibroblasts, circulating blood neutrophils, vascular endothelial cells, joint Synovial membrane cells, seminal fluid, prostate epithelium cells, and mammary ductal epithelial cells.[4][5][6][7]
The distribution of Alox15 in sub-human primates and, in particular, rodents differs significantly from that of human ALOX15; this, along with their different principal product formation (e.g. 12-HETE rather than 15-HETE) has made the findings of Alox15 functions in rat, mouse, or rabbit models difficult to extrapolate to the function of ALOX15 in humans.[2]
# Enzyme activities
## Lipoxygenase activity
ALOX15 and Alox15 enzymes are non-heme, iron-containing dioxygenases. They commonly catalyze the attachment of molecular oxygen O2 as a peroxy residue to polyunsaturated fatty acids (PUFA) that contain two carbon-carbon double bonds that for the human ALOX15 are located between carbons 10 and 9 and 7 and 6 as numbered counting backward from the last or omega (i.e. ω) carbon at the methyl end of the PUFA (these carbons are also termed ω-10 and ω-9 and ω-7 and ω-6). In PUFAs that do not have a third carbon-carbon double bound between their ω-13 and ω-12 carbons, human ALOX15 forms ω-6 peroxy intermediates; in PUFAs that do have this third double bound, human ALOX15 makes the ω-6 peroxy intermediate but also small amounts of the ω-9 peroxy intermediate. Rodent Alox15 enzymes, in contrast, produce almost exclusively ω-9 peroxy intermediates. Concurrently, ALOX15 and rodent Alox15 enzymes rearrange the carbon-carbon double bonds to bring them into the 1S-hydroxy-2E,4Z-diene configuration. ALOX15 and Alox15 enzymes act with a high degree of Stereospecificity to form products that position the hydroperoxy residue in the S stereoisomer configuration.[8]
## Lipohydroperoxidase activity
Human ALOX15 can also convert the peroxy PUFA intermediate to a cyclic ether with a three-atom ring, i.e. an epoxide intermediate that is attacked by a water molecule to form epoxy-hydrpoxy PUFA products.[2] Eoxins stimulate vascular permeability in an ex vivo human vascular endothelial model system.[9]
## Leukotriene synthase activity
The PUFA epoxide of arachidonic acid made by ALOX15 may also be conjugated with glutathione to form eoxin A4 which product can be further metabolized to eoxin B4, eoxin C4, and eoxin D4.[2]
# Substrates, substrate metabolites, and metabolite activities
Among their physiological substrates, human and rodent AlOX15 enzymes act on linoleic acid, alpha-linolenic acid, gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid when presented not only as free acids but also when incorporated as esters in phospholipids, glycerides, or Cholesteryl esters. The human enzyme is particularly active on linoleic acid, preferring it over arachidonic acid. It is less active on PUFA that are esters within the cited lipids.[2]
## Arachidonic acid
Arachidonic acid (AA) has double bonds between carbons 5-6, 8-9, 11-12, and 14-15; these double bonds are in the cis (see Cis–trans isomerism or Z as opposed to the trans or E configuration. ALOX15 adds a hydroperoxy residue to AA at carbons 15 and to a lesser extent 12 to form 15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15(S)-HpETE) and 12(S)-hydroperoxy-5Z,8Z,10E, 15S-eicosatetraenoic acid (12(S)-HpETE); the purified enzyme makes 15(S)-HpETE and 12(S)-HpETE in a product ratio of ~4-9 to 1.[10] Both products may be rapidly reduced by ubiquitous cellular Glutathione peroxidase enzymes to their corresponding hydroxy analogs, 15(S)-HETE (see 15-hydroxyeicosatetraenoic acid) and 12(S)-HETE (see 12-Hydroxyeicosatetraenoic acid). 15(S)-HpETE and 15(S)-HETE bind to and activate the Leukotriene B4 receptor 2, activate the Peroxisome proliferator-activated receptor gamma, and at high concentrations cause cells to generate toxic reactive oxygen species; one or more of these effects may be at least in part responsible for their ability to promote inflammatory responses, alter the growth of various times of human cancer cell lines, contract various types of blood vessels, and stimulate pathological fibrosis in pulmonary arteries and liver (see 15-Hydroxyicosatetraenoic acid#15(S)-HpETE and 15(S)-HETE). 15(S)-HpETE and 15(S)-HETE are esterified into membrane phospholipids where they may be stored and subsequently released during cell stimulation. As one aspect of this processing, the two products are progressively esterified in mitochondria membrane phospholipids during the maturation of red blood cells (see erythropoiesis) and thereby may serve to signal for the degradation of the mitochondria and the maturation of these precursors to red blood cells in mice. This pathway operates along with two other mitochondria-removing pathways and therefore does not appear essential for mouse red blood cell maturation.[2]
15-(S)-HpETE and 15(S)-HETE may be further metabolized to various bioactive products including:
- lipoxin (LX)A4, LXB4, AT-LXA4, and AT-LXB4; these metabolites are members of the specialized proresolving mediator class of anti-inflammatory agents that contribute to the resolution of inflammatory responses and inflammation-based diseases in animal models and, potentially, humans (see specialized proresolving mediators and lipoxins).
- Hepoxilin isomers (e.g. 1S-hydroxy-14S,15S-epoxy-5Z,8Z,12E-eicosatrienoic acid [14,15-HXA3] and 13R-hydroxy-14S,15S-epoxy-5Z,8Z,11Z-eicosatrienoic acid [14,15-HXB3]) which may contribute to the regulation of inflammation responses and insulin secretion (see hepoxilins).
- Eoxins (e.g. eoxin C4, 14,15-eoxin D4, and eoxin E4) which have pro-inflammatory actions and contribute to severe asthma, aspirin-induced asthma attacks, and other allergy reactions; they may also be involved in the pathology of Hodgkins disease (see Eoxins).
- 8(S),15(S)-dihydroxy-5Z,9E,llZ,13E-eicosatetraenoic acid (8(S),15(S)-diHETE), an inhibitor of human platelet aggregation (see Dihydroxy-E,Z,E-PUFA).
- 5(S),15(S)-dihydroxy-6Z,8E,llE,13Z-eicosatetraenoic acid (5S),15(S)-diHETE) and its 5-ketone analog, 5-oxo-15(S)-hydroxy-ETE. These are weak and potent, respectively, stimulators of human eosinophil, neutrophil, and monocyte chemotaxis and thereby possible contributors to human allergic and non-allergic inflammation responses (see 5-Hydroxyicosatetraenoic acid#Inflammation and 5-Hydroxyicosatetraenoic acid#Allergy).
- 15-Oxo-ETE which inhibits the growth of cultured Human umbilical vein endothelial cells and various human cancer cell lines; it is also has activities on THP1 cell line cells suggesting that it might act as an inhibitor of inflammatory and oxidative stress reactions (see15-Hydroxyicosatetraenoic acid#15-oxo-ETE).
The minor products of ALOX15, 12-(S)-HpETE and 12(S)-HETE, possess a broad range of activities. One or both of these compounds stimulates cells by binding with and activating two G protein-coupled receptors, GPR31 and the Leukotriene B4 receptor 2; 12S-HETE also acts as a receptor antagonist by binding to but not stimulating the Thromboxane receptor thereby inhibiting the actions of Thromboxane A2 and Prostaglandin H2 (see 12-Hydroxyeicosatetraenoic acid#Receptor targets and mechanisms of action). As at least a partial consequence of these receptor-directed actions, one or both the two ALOX15 products exhibit pro-inflammation, diabetes-inducing, and vasodilation activities in animal models; cancer-promoting activity on cultured human cancer cells; and other actions (see 12-Hydroxyeicosatetraenoic acid#Activities and possible clinical significance). The two products are also further metabolized to various bioactive products including:
- Hepoxilin A3 and Hepoxilin B3 along with their respective tri-hydroxyl metabolites, trioxilin A3 and trioxilin B3. These metabolites have been reported to have anti-inflammatory activity, to have vasodilationactivity, to promote pain perceptrion, to reverse oxidative stress in cells, and to promote insulin secretion in animal model systems (see Hepoxilin.
- 12-Oxo-ETE, which along with 12S-HETE, activates the Leukotriene B4 receptor, Leukotriene B4 receptor 2 (BLT2) but not its Leukotriene B4 receptor 1 (BLT1). This allows the possibility that 12-oxo-ETE contributes to the pro-inflammatory and other activities that BLT2 regulates (see 12-HETE#Inflammation and inflammatory diseases and Leukotriene B4 receptor 2.[11]
## Docosahexaenoic acid
Human ALOX15 metabolizes docosahexaenoic acid (DHA) to 17S-Hydroperoxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid (17S-HpDHA) and 17S-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid (17S-HDHA).[12] One or both of these products stimulate human breast and prostate cell lines to proliferate in culture and 17S-HDHA possesses potent specialized proresolving mediator activity (see specialized proresolving mediators#DHA-derived Resolvins).[13][14][15][16] One or both of these products may be further metabolized enzymatically to:
- Resolvin Ds (RvDs), i.e. RvD-1, RvD2, RvD3, RvD4, RvD5, and RvD6 (see resolvin and specialized proresolving mediators#DHA-derived Resolvins) and protectin Ds (PDs), i.e. PD1, PDX, 20-hydroxy-PD1, 17-epi-PD1, and 10-epi-PD1 (see neuroprotectin D1 and specialized proresolving mediators#DHA-derived protectins/neuroprotectins). These products are members of, and have a wide range of activities common to, the specialized proresolving mediators class of metabolites.
## Eicosapentaenoic acid
Human ALOX15 metabolizes eicosapentaenoic acid to 15S-hydroperoxy-5Z,8Z,11Z,13E,17E-eicosapentaenoic acid (15S-HpEPA) and 15S-hydroxy-5Z,8Z,11Z,13E,17E-eicosapentaenoic acid (15S-HEPA); 15S-HEPA inhibits ALOX5-dependent production of the pro-inflammatory mediator, LTB4, in cells, and may thereby serve an anti-inflammatory function.[17] These products may be further metabolized to:
- Resolvin E3, a specialized proresolvin mediator with anti-inflammatory activity (see Specialized proresolving mediators#EPA-derived resolvins (i.e. RvE)).
## n-3 Docosaexaenoic acid
Human cells and mouse tissues metabolize n-3 docosapentaenoic acid (i.e., 7Z,10Z,13Z,16Z,19Z-docosapentaenoic acid, see clupanodonic acid) to a series of products that have been classified as specialized proresolvin mediators. Base on the analogy to docosahexaenoic acid metabolism to resolving D's, it is presumed that a 15-lipoxygenase, most likely ALOX15 in humans, contributes to this metabolism. These products, termed n-3 Resolven D's (RvDn-3's), are:
- RvD1n-3, RvD2n-3, and RvD3n-3; each of these products possesses potent anti-inflammatory activity (see Specialized proresolving mediators#n-3 DPA-derived resolvins).
## Linoleic acid
Human 15-LOX-1 prefers linoleic acid over arachidonic acid as its primary substrate, oxygenating it at carbon 13 to form 13(S)-hydroperoxy-9Z,11E-octadecaenoic acid (13-HpODE or 13(S)-HpODE) which may then be reduce to the corresponding hydroxy derivative, 13(S)-HODE or 13-HODE (see 13-Hydroxyoctadecadienoic acid). In addition to 13(S)-HpODE, non-human 15-LOX1 orthologs such as mouse 12/15-LOX and soybean 15-LOX metabolize linoleic acid to 9-hydroperoxy-10E, 12Z-octadecaenoic acid (9-HpODE or 9(S)-HpODE), which is rapidly converted to 9(S)-HODE (9-HODE) (see 9-Hydroxyoctadecadienoic acid)).[18][19] 13(S)-HODE acts through Peroxisome proliferator-activated receptors and the TRPV1 and human GPR132 receptors to stimulate a variety of responses related to monocyte maturation, lipid metabolism, and neuron activation (see 13-Hydroxyoctadecadienoic acid##Activities of 13-HODEs; 9(S)-HODE is a marker for diseases involving oxidative stress and may contribute to this disease as well as to pain perception and atherosclerosis (see 9-Hydroxyoctadecadienoic acid##Biological and clinical relevancy of 9-HODEs). The two HODEs can be further metabolized to their ketones, 13-oxo-9Z,11E-octadecaenoic acid and 9-oxo-10E, 12Z-octadecaenoic acid; these ketones have been implicated as biomarkers for and possible contributors to the inflammatory component of atherosclerosis, Alzheimer's disease, Steatohepatitis, and other pathological conditions.[20]
## Dihomo-γ-linolenic acid
Human neutrophils, presumably using their ALOX 15, metabolize Dihomo-γ-linolenic acid (8Z,11Z,14Z-eicosatrienoic acid) to 15S-hydroperoxy-8Z,11Z,13E-eicosatrienoic acid and 15S-hydroxy-8Z,11Z,13E-eicosatrienoic acid (15S-HETrE). 15S-HETrE possesses anti-inflammatory activity.[17][21]
# Gene manipulation studies
Mice made deficient in their 12/15-lipoxygenase gene (Alox15) exhibit a prolonged inflammatory response along with various other aspects of a pathologically enhanced inflammatory response in experimental models of cornea injury, airway inflammation, and peritonitis. These mice also show an accelerated rate of progression of atherosclerosis whereas mice made to overexpress 12/15-lipoxygenase exhibit a delayed rate of atherosclerosis development. Alox15 overexpressing rabbits exhibited reduced tissue destruction and bone loss in a model of periodontitis. Finally, Control mice, but not 12/15-lipoxygense deficient mice responded to eicospentaenoic acid administration by decreasing the number of lesions in a model of endometriosis.[22] These studies indicate that the suppression of inflammation is a major function of 12/15-lipoxygenase and the Specialized proresolving mediators it produces in rodents; although rodent 12/15-lipoxygenase differs from human ALOX15 in the profile of the PUFA metabolites that it produces as well as various other parameters (e.g. tissue distribution), these genetic studies allow that human ALOX15 and the specialized proresolving mediators it produces may play a similar major anti-inflammatory function in humans.
# Clinical significance
## Inflammatory diseases
À huge and growing number of studies in animal models suggest that 15-LOX-1 and its lipoxin, resolvin, and protectin metabolites (see Specialized proresolving mediators) to inhibit, limit, and resolve diverse inflammatory diseases including periodontitis, peritonitis, sepsis, and other pathogen-induced inflammatory responses; in eczema, arthritis, asthma, cystic fibrosis, atherosclerosis, and adipose tissue inflammation; in the insulin resistance that occurs in obesity that is associated with diabetes and the metabolic syndrome; and in Alzheimer's disease.[23][24][25][26][27] While these studies have not yet been shown to translate to human diseases, first and second generation synthetic resolvins and lipoxins, which unlike their natural analogs, are relatively resistant to metabolic inactivation, have been made and tested as inflammation inhibitors in animal models.[28] These synthetic analogs may prove to be clinically useful for treating the cited human inflammatory diseases.
By metabolizing the ω-3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid, into 17-HpDHA, 17-HDHA, and the resolvins and protectins, 15-LOX-1's metabolic action is thought to be one mechanism by which dietary ω-3 polyunsaturated fatty acids, particularly fish oil, act to ameliorate inflammation, inflammation-related diseases, and certain cancers.[7][23]
## Asthma
15-LOX-1 and its 5-oxo-15-hydroxy-ETE and eoxin metabolites have been suggested as potential contributors to, and therefore targets for the future study and treatment of, human allergen-induced asthma, aspirin-induced asthma, and perhaps other allergic diseases.[29][30]
## Cancer
In colorectal, breast, and kidney cancers, 15-LOX-1 levels are low or absent compared to the cancers' normal tissue counterparts and/or these levels sharply decline as the cancers progress.[6][23][31] These results, as well as a 15-LOX-1 transgene study on colon cancer in mice[32] suggests but do not prove[33] that 15-LOX-1 is a tumor suppressor.
By metabolizing ω-3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid, into lipoxins and resolvins, 15-LOX-1 is thought to be one mechanism by which dietary ω-3 polyunsaturated fatty acids, particularly fish oil, may act to reduce the incidence and/or progression of certain cancers.[23] Indeed, the ability of docosahexaenoic acid to inhibit the growth of cultured human prostate cancer cells is totally dependent upon the expression of 15-LOX-1 by these cells and appears due to this enzyme's production of docosahexaenoic acid metabolites such as 17(S)-HpETE, 17(S)-HETE, and/or and, possibly, an isomer of protectin DX (10S, 17S-dihydroxy-4Z, 7Z, 11E, 13Z, 15E, 19Z-docosahexaenoic acid)[7][34]
Kelavkar et.al have shown that aberrant overexpression of 15-LO-1 occurs in human PCa, particularly high-grade PCa, and in high-grade prostatic intraepithelial neoplasia (HGPIN), and that the murine orthologue is increased in SV40-based genetically engineered mouse (GEM) models of PCa, such as LADY and TRansgenic Adenocarcinoma of Mouse Prostate.Targeted overexpression of h15-LO-1 (a gene overexpressed in human PCa and HGPIN) to mouse prostate is sufficient to promote epithelial proliferation and mPIN development. These results support 15-LO-1 as having a role in prostate tumor initiation and as an early target for dietary or other prevention strategies. The FLiMP mouse model should also be useful in crosses with other GEM models to further define the combinations of molecular alterations necessary for PCa progression.[35] | https://www.wikidoc.org/index.php/ALOX15 | |
287a3063cea5b412ea2c878106ccf5ba5ec196bf | wikidoc | ALOXE3 | ALOXE3
Epidermis-type lipoxygenase 3 (ALOXE3 or eLOX3) is a member of the lipoxygenase family of enzymes; in humans, it is encoded by the ALOXE3 gene. This gene is located on chromosome 17 at position 13.1 where it forms a cluster with two other lipoxygenases, ALOX12B and ALOX15B. Among the human lipoxygenases, ALOXE3 is most closely (54% identity) related in amino acid sequence to ALOX12B. ALOXE3, ALOX12B, and ALOX15B are often classified as epidermal lipoxygenases, in distinction to the other three human lipoxygenases (ALOX5, ALOX12, and ALOX15), because they were initially defined as being highly or even exclusively expressed and functioning in skin. The epidermis-type lipoxygenases are now regarded as a distinct subclass within the multigene family of mammalian lipoxygenases with mouse Aloxe3 (also termed e-Lox-3) being the ortholog to human ALOXE3, mouse Alox12b being the ortholog to human ALOX12B (MIM 603741), and mouse Alox8 being the ortholog to human ALOX15B (MIM 603697). ALOX12B and ALOXE3 in humans, Alox12b and Aloxe3 in mice, and comparable orthologs in other in other species are proposed to act sequentially in a multistep metabolic pathway that forms products that are structurally critical for creating and maintaining the skin's water barrier function.
# Tissue distribution
Immunologically detected ALOXE3 and ALOX12B in humans and Aloxe3 and Alox12b in mice have a similar tissue distribution in being highly expressed in the outer, differentiated layers of the epidermis; they co-localize at the surface of keratinocytes in the stratum granulosum of mouse skin and during mouse embryogenesis appear concurrently at the onset of skin development at day 15.5. ALOXE3 mRNA in humans was also detected at low levels in the pancreas, ovary, brain, testis, placenta, and some secretory epithelia. Aloxe3 and Alox12b mRNA was detected in the tongue, forestomach, trachea, brain, testis, and adipose tissue of mice and in the spinal cord of rats.
# Activity
## Epidermal tissue
ALOX12B, like most of the other lipoxygenases, possesses dioxygenase (EC 1.13.11) activity: it catalyzes the incorporate dioxygen (i.e. molecular oxygen ) into a single substrate. Owing to this activity, the enzyme adds (O2) in the form of a hydroperoxyl (HO2) residue to arachidonic acid at its 12th carbon thereby forming 12(R)-hydroperoxy-5Z,8Z,10E,14Z-icosatetraenoic acid (also termed 12(R)-HpETE or 12R-HpETE).
arachidonic acid + O2 \rightleftharpoons 12R-HpETE
Hydroperoxy-containing polyunsaturated fatty acids (PUFAs) such as 12R-HETE readily breakdown through non-enzymatic transformations in which the two oxygen atoms of the hydroperoxy residue rearrange to form PUFAs containing one hydroxyl (also termed alcohol) residue and one epoxide residue. This transformation may occur in tissues or during tissue preparations with 12-HpETE to form Hepoxilins, i.e. epoxyalcohols of 12-HpETE that are of the A type (i.e. hepoxilin As, which contain an epoxy and alcohol residue separated from each other by a double (i.e. alkene) bond or, alternatively, B type (i.e. hepoxilin Bs, which contain epoxy and alcohol residues on adjacent carbons); these non-enxymatically formed products are a mixture of hydroxy and epoxy R,S stereoisomers and diastereomers. In addition to arachidonic acid, ALOX12B metabolizes linoleic acid (LA) to 9(R)-hydroperoxy-10(E),12(Z)-octadecadienoic acid (9R-HpODE):
LA + O2 \rightleftharpoons9R-HpODE.
ALOXE3 is an atypical lipoxygenase in that under most but not all experimental conditions, it lacks the dioxygenase activity that converts PUFA to hydroperoxide metabolites; rather, it possess hepoxilin synthase (i.e. hydroperoxy isomerase) activity; that is, it converts hydroperoxy-containing PUFAs to hepoxilin-like epoxyalcohol products; these products, unlike those formed by non-enzymatic transformations, are specific isomers with just one form of the chiral hydroxy and epoxy residues. ALOX3E metabolizes 12R-HpETE to 8R-hydroxy-11R,12R-epoxy-eicosatrienoic acid and metabolizes 9R-HpODE to products that contain either an epoxyalcohol or a ketone residue. It exhibits relatively weak activity in conducting this conversion on free 9R-HODE but stronger activity when 9R-HpODE is presented as its methyl ester. ALOXE3's primary function in epidermal tissue appears to be to metabolize the 9R-HpODE moiety that is not free but rather esterified to certain ceramide lipids.
LA is the most abundant fatty acid in the skin epidermis, being present mainly esterified to the omega-hydroxyl residue of amide-linked omega-hydroxylated very long chain fatty acids (VLCFAs) in a unique class of ceramides termed esterified omega-hydroxyacyl-sphingosine (EOS). EOS is an intermediate component in a proposed multi-step metabolic pathway which delivers VLCFAs to the cornified lipid envelop in the skin's Stratum corneum; the presence of these wax-like, hydrophobic VLCFAs is needed to maintain the skin's integrity and functionality as a water barrier (see Lung microbiome#Role of the epithelial barrier). ALOX12B metabolizes the LA in EOS to its 9R-hydroperoxy derivative which ALOXE3 then converts to three ceramide-esterified products: a) 9R,10R-trans-epoxide,13R-hydroxy-10E-octadecenoic acid, b) 9-keto-10E,12Z-octadecadienoic acid, and c) 9R,10R-trans-epoxy-13-keto-11E-octadecenoic acid. The ALOX12B/ALOE3-oxidized products, it is proposed, signal for their hydrolysis (i.e. removal) from EOS; this allows the multi-step metabolic pathway to proceed in delivering the VLCFAs to the cornified lipid envelop in the skin's Stratum corneum.
## Other tissues
AloxE3 appears responsible for forming hepoxilins A and/or B from 12R-HpETE in the spinal fluids of rats and ALOXE3 is proposed to be responsible for the formation of these hepoxilins in various human tissues although the presence and activity of ALOXE3 in many of these hepoxilin-forming tissues has not yet been demonstrated.
Spinal Aloxe3, apparently through its ability to make hepoxilins, appears responsible for the hyperalgesia which accompanies inflammation in rats.
Aloxe3 appears necessary and sufficient for the differentiation of mouse 3T3-L1 fibroblast cells into adipocytes (i.e. fat cells); the function of Aloxe3 in this differentiation appears to be to its metabolism 12R-HpETE into hepoxilins A3 or B3 which directly activate(s) Peroxisome proliferator-activated receptor gamma which in turn initiates the expression of adipocyte-differentiation genes.
# Clinical significance
## Congenital ichthyosiform erythrodema
Deletions of Alox12b or Aloxe3 genes by gene knockout in mice cause a congenital scaly skin disease which is characterized by a greatly reduced skin water barrier function and other features found in the autosomal recessive nonbullous Congenital ichthyosiform erythroderma (ARCI) disease of humans.; homoxzygous recessive deleterious mutations in ALOXE3 or ALOX12B are likewise causes, albeit rare, of this congenital disease in humans. ARCI refers to nonsyndromic (i.e. not associated with other signs or symptoms) congenital Ichthyosis including Harlequin-type ichthyosis, Lamellar ichthyosis, and Congenital ichthyosiform erythroderma. ARCI has an incidence of about 1/200,000 in European and North American populations; 40 different mutations in ALOX12B and 13 different mutations in ALOXE3 genes account for a total of about 10% of ARCI cases; these mutations are homoxygous recessive (see Dominance (genetics)), cause a total loss of ALOX12B or ALOXE3 function (see mutations), and can be associated with any of the three cited forms of the disease.
## Hepoxilin synthase
In mice lacking Aloxe3 activity due to gene knockout of the Alox3 gene, levels in skin of hepoxilins A3 and B3, as well as their metabolites, trioxilins A3 and B3, are greatly reduced. Furthermore, rat Aloxe3 has been implicated in the production of hepoxilin B3 in studies that transfected its gene into cultured HEK 293 cells and similarly implicated in the inflammation-induced production of hepoxilin B3 in the spine of rats as well as the perception of pain (i.e. allodynia) by these animals using pharmacological inhibitor and siRNA-based gene knockdown studies. Finally, cultured human skin cells, which are rich in ALOXE3 readily convert arachidonic acid as well as 12S-hydroperoxy-eicosatetraenoic acid to Hepoxilin B3; this production, in keeping with the higher content of ALOXE3, is far greater in the skin cells isolated from subjects with psoriasis. These results suggest that ALOXE3 and its orthologs contribute greatly to or are the hepoxylin synthase activity responsible for producing bioactive hepoxilins (see hepoxilin) in the skin and other ALOXE3/ortholog-rich tissues of mammals, possibly including humans.
## Other possible clinical significances
The distribution of ALOXE3 and Aloxe3 (see Tissue distribution, above) suggests that these lipoxygenases may serve functions not only in the skin but also in other tissues. The studies reported in the above "Activities, Other tissues", subsection allow that the pain perception and adipocyte differentiation activities of Aloxe3 in rodents might also occur in humans.
# Toxicity
Interuterine delivery of e-Lox-3 to mice at gestational day 14.5 resulted in fetal growth restriction and intrauterine death apparently due to a strongly negative effect on placental development. | ALOXE3
Epidermis-type lipoxygenase 3 (ALOXE3 or eLOX3) is a member of the lipoxygenase family of enzymes; in humans, it is encoded by the ALOXE3 gene.[1] This gene is located on chromosome 17 at position 13.1 where it forms a cluster with two other lipoxygenases, ALOX12B and ALOX15B.[2] Among the human lipoxygenases, ALOXE3 is most closely (54% identity) related in amino acid sequence to ALOX12B.[3][4][5] ALOXE3, ALOX12B, and ALOX15B are often classified as epidermal lipoxygenases, in distinction to the other three human lipoxygenases (ALOX5, ALOX12, and ALOX15), because they were initially defined as being highly or even exclusively expressed and functioning in skin. The epidermis-type lipoxygenases are now regarded as a distinct subclass within the multigene family of mammalian lipoxygenases with mouse Aloxe3 (also termed e-Lox-3) being the ortholog to human ALOXE3, mouse Alox12b being the ortholog to human ALOX12B (MIM 603741), and mouse Alox8 being the ortholog to human ALOX15B (MIM 603697)[supplied by OMIM].[1] ALOX12B and ALOXE3 in humans, Alox12b and Aloxe3 in mice, and comparable orthologs in other in other species are proposed to act sequentially in a multistep metabolic pathway that forms products that are structurally critical for creating and maintaining the skin's water barrier function.
# Tissue distribution
Immunologically detected ALOXE3 and ALOX12B in humans and Aloxe3 and Alox12b in mice have a similar tissue distribution in being highly expressed in the outer, differentiated layers of the epidermis; they co-localize at the surface of keratinocytes in the stratum granulosum of mouse skin and during mouse embryogenesis appear concurrently at the onset of skin development at day 15.5.[6] ALOXE3 mRNA in humans was also detected at low levels in the pancreas, ovary, brain, testis, placenta, and some secretory epithelia.[6][7] Aloxe3 and Alox12b mRNA was detected in the tongue, forestomach, trachea, brain, testis, and adipose tissue of mice and in the spinal cord of rats.[6]
# Activity
## Epidermal tissue
ALOX12B, like most of the other lipoxygenases, possesses dioxygenase (EC 1.13.11) activity: it catalyzes the incorporate dioxygen (i.e. molecular oxygen [O2]) into a single substrate. Owing to this activity, the enzyme adds (O2) in the form of a hydroperoxyl (HO2) residue to arachidonic acid at its 12th carbon thereby forming 12(R)-hydroperoxy-5Z,8Z,10E,14Z-icosatetraenoic acid (also termed 12(R)-HpETE or 12R-HpETE).[8][9]
arachidonic acid + O2 <math>\rightleftharpoons</math> 12R-HpETE
Hydroperoxy-containing polyunsaturated fatty acids (PUFAs) such as 12R-HETE readily breakdown through non-enzymatic transformations in which the two oxygen atoms of the hydroperoxy residue rearrange to form PUFAs containing one hydroxyl (also termed alcohol) residue and one epoxide residue.[10] This transformation may occur in tissues or during tissue preparations with 12-HpETE to form Hepoxilins, i.e. epoxyalcohols of 12-HpETE that are of the A type (i.e. hepoxilin As, which contain an epoxy and alcohol residue separated from each other by a double (i.e. alkene) bond or, alternatively, B type (i.e. hepoxilin Bs, which contain epoxy and alcohol residues on adjacent carbons); these non-enxymatically formed products are a mixture of hydroxy and epoxy R,S stereoisomers and diastereomers.[11] In addition to arachidonic acid, ALOX12B metabolizes linoleic acid (LA) to 9(R)-hydroperoxy-10(E),12(Z)-octadecadienoic acid (9R-HpODE):[11]
LA + O2 <math>\rightleftharpoons</math>9R-HpODE.
ALOXE3 is an atypical lipoxygenase in that under most but not all experimental conditions, it lacks the dioxygenase activity that converts PUFA to hydroperoxide metabolites; rather, it possess hepoxilin synthase (i.e. hydroperoxy isomerase) activity; that is, it converts hydroperoxy-containing PUFAs to hepoxilin-like epoxyalcohol products; these products, unlike those formed by non-enzymatic transformations, are specific isomers with just one form of the chiral hydroxy and epoxy residues. ALOX3E metabolizes 12R-HpETE to 8R-hydroxy-11R,12R-epoxy-eicosatrienoic acid[11] and metabolizes 9R-HpODE to products that contain either an epoxyalcohol or a ketone residue.[6][12] It exhibits relatively weak activity in conducting this conversion on free 9R-HODE but stronger activity when 9R-HpODE is presented as its methyl ester. ALOXE3's primary function in epidermal tissue appears to be to metabolize the 9R-HpODE moiety that is not free but rather esterified to certain ceramide lipids.
LA is the most abundant fatty acid in the skin epidermis, being present mainly esterified to the omega-hydroxyl residue of amide-linked omega-hydroxylated very long chain fatty acids (VLCFAs) in a unique class of ceramides termed esterified omega-hydroxyacyl-sphingosine (EOS). EOS is an intermediate component in a proposed multi-step metabolic pathway which delivers VLCFAs to the cornified lipid envelop in the skin's Stratum corneum; the presence of these wax-like, hydrophobic VLCFAs is needed to maintain the skin's integrity and functionality as a water barrier (see Lung microbiome#Role of the epithelial barrier).[6] ALOX12B metabolizes the LA in EOS to its 9R-hydroperoxy derivative which ALOXE3 then converts to three ceramide-esterified products: a) 9R,10R-trans-epoxide,13R-hydroxy-10E-octadecenoic acid, b) 9-keto-10E,12Z-octadecadienoic acid, and c) 9R,10R-trans-epoxy-13-keto-11E-octadecenoic acid.[6][12] The ALOX12B/ALOE3-oxidized products, it is proposed, signal for their hydrolysis (i.e. removal) from EOS; this allows the multi-step metabolic pathway to proceed in delivering the VLCFAs to the cornified lipid envelop in the skin's Stratum corneum.[6][13]
## Other tissues
AloxE3 appears responsible for forming hepoxilins A and/or B from 12R-HpETE in the spinal fluids of rats[14] and ALOXE3 is proposed to be responsible for the formation of these hepoxilins in various human tissues[11][15] although the presence and activity of ALOXE3 in many of these hepoxilin-forming tissues has not yet been demonstrated.
Spinal Aloxe3, apparently through its ability to make hepoxilins, appears responsible for the hyperalgesia which accompanies inflammation in rats.[14]
Aloxe3 appears necessary and sufficient for the differentiation of mouse 3T3-L1 fibroblast cells into adipocytes (i.e. fat cells); the function of Aloxe3 in this differentiation appears to be to its metabolism 12R-HpETE into hepoxilins A3 or B3 which directly activate(s) Peroxisome proliferator-activated receptor gamma which in turn initiates the expression of adipocyte-differentiation genes.[16]
# Clinical significance
## Congenital ichthyosiform erythrodema
Deletions of Alox12b or Aloxe3 genes by gene knockout in mice cause a congenital scaly skin disease which is characterized by a greatly reduced skin water barrier function and other features found in the autosomal recessive nonbullous Congenital ichthyosiform erythroderma (ARCI) disease of humans.;[12] homoxzygous recessive deleterious mutations in ALOXE3 or ALOX12B are likewise causes, albeit rare, of this congenital disease in humans.[17][18] ARCI refers to nonsyndromic (i.e. not associated with other signs or symptoms) congenital Ichthyosis including Harlequin-type ichthyosis, Lamellar ichthyosis, and Congenital ichthyosiform erythroderma.[6] ARCI has an incidence of about 1/200,000 in European and North American populations; 40 different mutations in ALOX12B and 13 different mutations in ALOXE3 genes account for a total of about 10% of ARCI cases; these mutations are homoxygous recessive (see Dominance (genetics)), cause a total loss of ALOX12B or ALOXE3 function (see mutations), and can be associated with any of the three cited forms of the disease.[6][19]
## Hepoxilin synthase
In mice lacking Aloxe3 activity due to gene knockout of the Alox3 gene, levels in skin of hepoxilins A3 and B3, as well as their metabolites, trioxilins A3 and B3, are greatly reduced.[11][20] Furthermore, rat Aloxe3 has been implicated in the production of hepoxilin B3 in studies that transfected its gene into cultured HEK 293 cells and similarly implicated in the inflammation-induced production of hepoxilin B3 in the spine of rats as well as the perception of pain (i.e. allodynia) by these animals using pharmacological inhibitor and siRNA-based gene knockdown studies.[14] Finally, cultured human skin cells, which are rich in ALOXE3 readily convert arachidonic acid as well as 12S-hydroperoxy-eicosatetraenoic acid to Hepoxilin B3; this production, in keeping with the higher content of ALOXE3, is far greater in the skin cells isolated from subjects with psoriasis.[6][11] These results suggest that ALOXE3 and its orthologs contribute greatly to or are the hepoxylin synthase activity responsible for producing bioactive hepoxilins (see hepoxilin) in the skin and other ALOXE3/ortholog-rich tissues of mammals, possibly including humans.
## Other possible clinical significances
The distribution of ALOXE3 and Aloxe3 (see Tissue distribution, above) suggests that these lipoxygenases may serve functions not only in the skin but also in other tissues. The studies reported in the above "Activities, Other tissues", subsection allow that the pain perception and adipocyte differentiation activities of Aloxe3 in rodents might also occur in humans.
# Toxicity
Interuterine delivery of e-Lox-3 to mice at gestational day 14.5 resulted in fetal growth restriction and intrauterine death apparently due to a strongly negative effect on placental development. | https://www.wikidoc.org/index.php/ALOXE3 | |
fb3c866b83893ae32641c492f0e88588119f1e89 | wikidoc | ANAPC1 | ANAPC1
Anaphase-promoting complex subunit 1 is an enzyme that in humans is encoded by the ANAPC1 gene.
ANAPC1 is one of at least ten subunits of the anaphase-promoting complex (APC), which functions at the metaphase-to-anaphase transition of the cell cycle and is regulated by spindle checkpoint proteins. The APC is an E3 ubiquitin ligase that targets cell cycle regulatory proteins for degradation by the proteasome, thereby allowing progression through the cell cycle (supplied by OMIM).
# Interactions
ANAPC1 has been shown to interact with ANAPC5, ANAPC4, ANAPC2, CDC27 and ANAPC7. | ANAPC1
Anaphase-promoting complex subunit 1 is an enzyme that in humans is encoded by the ANAPC1 gene.[1][2]
ANAPC1 is one of at least ten subunits of the anaphase-promoting complex (APC), which functions at the metaphase-to-anaphase transition of the cell cycle and is regulated by spindle checkpoint proteins. The APC is an E3 ubiquitin ligase that targets cell cycle regulatory proteins for degradation by the proteasome, thereby allowing progression through the cell cycle (supplied by OMIM).[2]
# Interactions
ANAPC1 has been shown to interact with ANAPC5,[3][4] ANAPC4,[3][4] ANAPC2,[3][4] CDC27[3][4] and ANAPC7.[3][4] | https://www.wikidoc.org/index.php/ANAPC1 | |
9483eaf11ac1df302c38050cdfeaf9bd3f96841f | wikidoc | ANAPC4 | ANAPC4
Anaphase-promoting complex subunit 4 is an enzyme that in humans is encoded by the ANAPC4 gene.
A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition by ubiquitinating its specific substrates such as mitotic cyclins and anaphase inhibitor, which are subsequently degraded by the 26S proteasome. Biochemical studies have shown that the vertebrate APC contains eight subunits. The composition of the APC is highly conserved in organisms from yeast to humans. The exact function of this gene product is not known.
# Interactions
ANAPC4 has been shown to interact with ANAPC1, ANAPC5, CDC27 and ANAPC7. | ANAPC4
Anaphase-promoting complex subunit 4 is an enzyme that in humans is encoded by the ANAPC4 gene.[1][2]
A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition by ubiquitinating its specific substrates such as mitotic cyclins and anaphase inhibitor, which are subsequently degraded by the 26S proteasome. Biochemical studies have shown that the vertebrate APC contains eight subunits. The composition of the APC is highly conserved in organisms from yeast to humans. The exact function of this gene product is not known.[2]
# Interactions
ANAPC4 has been shown to interact with ANAPC1,[3][4] ANAPC5,[3] CDC27[3][5] and ANAPC7.[3] | https://www.wikidoc.org/index.php/ANAPC4 | |
4fde9a3ab8db32628749b7f748f639435de33ca9 | wikidoc | ANAPC5 | ANAPC5
Anaphase-promoting complex subunit 5 is an enzyme that in humans is encoded by the ANAPC5 gene.
The anaphase-promoting complex (APC) consists of at least 8 protein subunits, including APC5, CDC27 (APC3; MIM 116946), CDC16 (APC6; MIM 603461), and CDC23 (APC8; MIM 603462).
# Interactions
ANAPC5 has been shown to interact with ANAPC1, ANAPC4, CDC27 and PABPC1. | ANAPC5
Anaphase-promoting complex subunit 5 is an enzyme that in humans is encoded by the ANAPC5 gene.[1][2]
The anaphase-promoting complex (APC) consists of at least 8 protein subunits, including APC5, CDC27 (APC3; MIM 116946), CDC16 (APC6; MIM 603461), and CDC23 (APC8; MIM 603462).[supplied by OMIM][2]
# Interactions
ANAPC5 has been shown to interact with ANAPC1,[3][4] ANAPC4,[3] CDC27[3][5][6] and PABPC1.[5] | https://www.wikidoc.org/index.php/ANAPC5 | |
1c4a49edd71b219760e1cff7e71c2f5ab609c4b8 | wikidoc | ANAPC7 | ANAPC7
Anaphase-promoting complex subunit 7 is an enzyme that in humans is encoded by the ANAPC7 gene. Multiple transcript variants encoding different isoforms have been found for this gene.
# Function
This gene encodes a tetratricopeptide repeat containing component of the anaphase-promoting complex/cyclosome (APC/C), a large E3 ubiquitin ligase that controls cell cycle progression by targeting a number of cell cycle regulators such as B-type cyclins for 26S proteasome-mediated degradation through ubiquitination. The encoded protein is required for proper protein ubiquitination function of APC/C and for the interaction of APC/C with certain transcription coactivators.
# Interactions
ANAPC7 has been shown to interact with ANAPC1, ANAPC4, CDC27 and CDC20. | ANAPC7
Anaphase-promoting complex subunit 7 is an enzyme that in humans is encoded by the ANAPC7 gene.[1] Multiple transcript variants encoding different isoforms have been found for this gene.
# Function
This gene encodes a tetratricopeptide repeat containing component of the anaphase-promoting complex/cyclosome (APC/C), a large E3 ubiquitin ligase that controls cell cycle progression by targeting a number of cell cycle regulators such as B-type cyclins for 26S proteasome-mediated degradation through ubiquitination. The encoded protein is required for proper protein ubiquitination function of APC/C and for the interaction of APC/C with certain transcription coactivators.[1]
# Interactions
ANAPC7 has been shown to interact with ANAPC1,[2][3] ANAPC4,[2] CDC27[2][4] and CDC20.[2][5] | https://www.wikidoc.org/index.php/ANAPC7 | |
8ddcb86ef6292904f8f59d263b8a849b672d2f1c | wikidoc | ANGPT4 | ANGPT4
Angiopoietin-4 is a protein that in humans is encoded by the ANGPT4 gene.
Angiopoietins are proteins with important roles in vascular development and angiogenesis.
All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor.
The mechanism by which they contribute to angiogenesis is thought to involve regulation of endothelial cell interactions with supporting perivascular cells.
The protein encoded by this gene functions as an agonist and is an angiopoietin. | ANGPT4
Angiopoietin-4 is a protein that in humans is encoded by the ANGPT4 gene.[1][2][3]
Angiopoietins are proteins with important roles in vascular development and angiogenesis.
All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor.
The mechanism by which they contribute to angiogenesis is thought to involve regulation of endothelial cell interactions with supporting perivascular cells.
The protein encoded by this gene functions as an agonist and is an angiopoietin.[3] | https://www.wikidoc.org/index.php/ANGPT4 | |
5e4ec0ab657a2d1b836f42ce5d0a5d1a2dda753f | wikidoc | ANKRD1 | ANKRD1
CARP, also known as Cardiac adriamycin-responsive protein or Cardiac ankyrin repeat protein is a protein that in humans is encoded by the ANKRD1 gene. CARP is highly expressed in cardiac and skeletal muscle, and is a transcription factor involved in development and under conditions of stress. CARP has been implicated in several diseases, including dilated cardiomyopathy, hypertrophic cardiomyopathy, and several skeletal muscle myopathies.
# Structure
Human CARP is a 36.2kDa protein composed of 319 amino acids., though in cardiomyocytes, CARP can exist as multiple alternatively spliced forms. CARP contains five tandem ankyrin repeats. Studies have shown that CARP can homodimerize. Studies have also shown that CARP is N-terminally, post-translationally cleaved by calpain-3 in skeletal muscle, suggesting alternate bioactive forms of CARP exist. CARP has been localized to nuclei and Z-discs in animal and human myocytes, and at intercalated discs in human cells.
# Function
CARP was originally identified as a YB-1-associating, cardiac-restricted transcription co-repressor in the homeobox NKX2-5 pathway that is involved in cardiac ventricular chamber specification, maturation and morphogenesis, and whose mRNA levels are exquisitely sensitive to Doxorubicin, mediated through a hydrogen peroxide/ERK/p38MAP kinase-dependent as well as M-CAT cis-element-dependent mechanism. Subsequent studies showed that CARP expression in cardiomyocytes is regulated by alpha-adrenergic signaling, in part via the transcription factor GATA4. An additional study showed that beta-adrenergic signaling via protein kinase A and CaM kinase induces the expression of CARP, and that CARP may have a negative effect on contractile function. CARP has also been identified as a transcriptional co-activator of tumor suppressor protein p53 for stimulating gene expression in muscle; p53 was found to be an upstream effector of CARP via upregulation of the proximal ANKRD1 promoter. CARP has a relatively short half-life being longer in cardiomyocytes than endothelial cells; and CARP is degraded by the 26S proteasome via a PEST degron.
In animal models of disease and injury, CARP has been characterized to be a stress-inducible myofibrillar protein. CARP has been shown to play a role in skeletal muscle structure remodeling, and repair, being expressed in skeletal muscle near myotendinous junctions, and in vascular smooth muscle cells, as a downstream target of TGF-beta/Smad sigmaling in response to balloon injury and atherosclerotic plaques. Further studies have identified a role for CARP in initiation and regulation of arteriogenesis. Decreased expression of CARP in cardiac cells within the ischemic region was detected in a rat model of ischemic injury, and was thought to be linked to the induction of GADD153, an apoptosis-related gene. In cardiomyocytes treated with doxorubicin, a model of anthracycline-induced cardiomyopathy, CARP mRNA and protein levels were depleted, myofilament gene transcription was attenuated and sarcomeres showed significant disarray.
In a transgenic mouse model of cardiac-specific overexpression of CARP, mice exhibited normal physiology at baseline, but were protected against pathological cardiac hypertrophy induced via pressure-overload or isoproterenol, which could be attributed to the downregulation of the ERK1/2, MEK and TGFbeta-1 pathways. Another study demonstrated that adenoviral overexpression of CARP in cardiomyocytes enhances cardiac hypertrophy induced by Angiotensin II or pressure-overload and promotoes cardiomyocyte apoptosis via p53 activation and mitochondrial dysfunction. However, transgenic knockout models of either CARP alone or CARP in combination with the other muscle ankyrin repeat proteins (MARPs), ANKRD2 and ANKRD23 demonstrated a lack of cardiac phenotype; mice displayed normal cardiac function at baseline and in response to pressure overload-induced cardiac hypertrophy, suggesting that these proteins are not essential.
Interactions between CARP and the sarcomeric proteins myopalladin and titin suggest that it may also be involved in the myofibrillar stretch-sensor system. Passive stretch in fetal cardiomyocytes induced differential CARP distribution at nuclei and I-band titin N2A regions. In a mouse model of muscular dystrophy with myositis (mdm) caused by a small deletion in titin, CARP mRNA expression was shown to be 30-fold elevated in skeletal muscle tissue.
# Clinical significance
A wide spectrum of clinical features have been associated with ANKRD1/CARP. Mutations in ANKRD1 have been associated with dilated cardiomyopathy, two of which result in altered binding with TLN1 and FHL2. Mutations in ANKRD1 have also been associated with hypertrophic cardiomyopathy, and have shown to increase binding of CARP to Titin and MYPN. Examination of the functional effects of CARP hypertrophic cardiomyopathy mutations in engineered heart tissue demonstrated that Thr123Met was a gain-of-function mutation exhibiting augmented contractile properties; whereas Pro52Ala and Ile280Val were unstable and failed to incorporate into sarcomeres, an effect that was remedied upon proteasome inhibition via epoxomicin.
A missense mutation in ANKRD1 was shown to be associated with the congenital heart defect, Anomalous pulmonary venous connection. CARP has been found as a sensitive and specific biomarker for the differential diagnosis of rhabdomyosarcoma. ANKRD1 mRNA levels correlate with patient platinum sensitivity, thus ANKRD1 associates with platinum-based chemotherapy treatment outcome in ovarian adenocarcinoma patients.
CARP and mRNA expression has been shown to be upregulated in left ventricles of heart failure patients. Studies in patients with amyotrophic lateral sclerosis, spinal muscular atrophy, and congenital myopathy, also found altered expression of CARP in skeletal muscle fibers. Another study in congenital muscular dystrophy and Duchenne muscular dystrophy patients showed elevated expression of CARP. CARP expression is also elevated in patients with lupus nephritis, and associates with proteinuria severity, suggesting that it may have biomarker potential.
# Interactions
ANKRD1 has been shown to interact with:
- Titin,
- MYPN,
- YBX1,
- CASQ2,
- DES,
- TP53,
- TLN1, and
- FHL2. | ANKRD1
CARP, also known as Cardiac adriamycin-responsive protein or Cardiac ankyrin repeat protein is a protein that in humans is encoded by the ANKRD1 gene.[1][2] CARP is highly expressed in cardiac and skeletal muscle, and is a transcription factor involved in development and under conditions of stress. CARP has been implicated in several diseases, including dilated cardiomyopathy, hypertrophic cardiomyopathy, and several skeletal muscle myopathies.
# Structure
Human CARP is a 36.2kDa protein composed of 319 amino acids.,[3] though in cardiomyocytes, CARP can exist as multiple alternatively spliced forms.[4] CARP contains five tandem ankyrin repeats. Studies have shown that CARP can homodimerize.[5] Studies have also shown that CARP is N-terminally, post-translationally cleaved by calpain-3 in skeletal muscle, suggesting alternate bioactive forms of CARP exist.[6] CARP has been localized to nuclei and Z-discs in animal and human myocytes, and at intercalated discs in human cells.[7]
# Function
CARP was originally identified as a YB-1-associating, cardiac-restricted transcription co-repressor in the homeobox NKX2-5 pathway that is involved in cardiac ventricular chamber specification, maturation and morphogenesis,[8][9][10] and whose mRNA levels are exquisitely sensitive to Doxorubicin, mediated through a hydrogen peroxide/ERK/p38MAP kinase-dependent[11][12] as well as M-CAT cis-element-dependent[13] mechanism. Subsequent studies showed that CARP expression in cardiomyocytes is regulated by alpha-adrenergic signaling, in part via the transcription factor GATA4.[14][15] An additional study showed that beta-adrenergic signaling via protein kinase A and CaM kinase induces the expression of CARP, and that CARP may have a negative effect on contractile function.[16] CARP has also been identified as a transcriptional co-activator of tumor suppressor protein p53 for stimulating gene expression in muscle; p53 was found to be an upstream effector of CARP via upregulation of the proximal ANKRD1 promoter.[17] CARP has a relatively short half-life being longer in cardiomyocytes than endothelial cells; and CARP is degraded by the 26S proteasome via a PEST degron.[18][19]
In animal models of disease and injury, CARP has been characterized to be a stress-inducible myofibrillar protein. CARP has been shown to play a role in skeletal muscle structure[20] remodeling,[21] and repair, being expressed in skeletal muscle near myotendinous junctions,[22] and in vascular smooth muscle cells, as a downstream target of TGF-beta/Smad sigmaling in response to balloon injury[23] and atherosclerotic plaques.[24] Further studies have identified a role for CARP in initiation and regulation of arteriogenesis.[25][26][27] Decreased expression of CARP in cardiac cells within the ischemic region was detected in a rat model of ischemic injury, and was thought to be linked to the induction of GADD153, an apoptosis-related gene.[28] In cardiomyocytes treated with doxorubicin, a model of anthracycline-induced cardiomyopathy, CARP mRNA and protein levels were depleted, myofilament gene transcription was attenuated and sarcomeres showed significant disarray.[29]
In a transgenic mouse model of cardiac-specific overexpression of CARP, mice exhibited normal physiology at baseline, but were protected against pathological cardiac hypertrophy induced via pressure-overload or isoproterenol, which could be attributed to the downregulation of the ERK1/2, MEK and TGFbeta-1 pathways.[30] Another study demonstrated that adenoviral overexpression of CARP in cardiomyocytes enhances cardiac hypertrophy induced by Angiotensin II or pressure-overload[31] and promotoes cardiomyocyte apoptosis via p53 activation and mitochondrial dysfunction.[32] However, transgenic knockout models of either CARP alone or CARP in combination with the other muscle ankyrin repeat proteins (MARPs), ANKRD2 and ANKRD23 demonstrated a lack of cardiac phenotype; mice displayed normal cardiac function at baseline and in response to pressure overload-induced cardiac hypertrophy, suggesting that these proteins are not essential.[33]
Interactions between CARP and the sarcomeric proteins myopalladin and titin suggest that it may also be involved in the myofibrillar stretch-sensor system. Passive stretch in fetal cardiomyocytes induced differential CARP distribution at nuclei and I-band titin N2A regions.[34] In a mouse model of muscular dystrophy with myositis (mdm) caused by a small deletion in titin, CARP mRNA expression was shown to be 30-fold elevated in skeletal muscle tissue.[35]
# Clinical significance
A wide spectrum of clinical features have been associated with ANKRD1/CARP. Mutations in ANKRD1 have been associated with dilated cardiomyopathy, two of which result in altered binding with TLN1 and FHL2.[36][37] Mutations in ANKRD1 have also been associated with hypertrophic cardiomyopathy, and have shown to increase binding of CARP to Titin and MYPN.[38] Examination of the functional effects of CARP hypertrophic cardiomyopathy mutations in engineered heart tissue demonstrated that Thr123Met was a gain-of-function mutation exhibiting augmented contractile properties; whereas Pro52Ala and Ile280Val were unstable and failed to incorporate into sarcomeres, an effect that was remedied upon proteasome inhibition via epoxomicin.[39]
A missense mutation in ANKRD1 was shown to be associated with the congenital heart defect, Anomalous pulmonary venous connection.[40] CARP has been found as a sensitive and specific biomarker for the differential diagnosis of rhabdomyosarcoma.[41] ANKRD1 mRNA levels correlate with patient platinum sensitivity, thus ANKRD1 associates with platinum-based chemotherapy treatment outcome in ovarian adenocarcinoma patients.[42]
CARP and mRNA expression has been shown to be upregulated in left ventricles of heart failure patients.[43][44][45][46] Studies in patients with amyotrophic lateral sclerosis,[47] spinal muscular atrophy, and congenital myopathy,[48] also found altered expression of CARP in skeletal muscle fibers. Another study in congenital muscular dystrophy and Duchenne muscular dystrophy patients showed elevated expression of CARP.[49] CARP expression is also elevated in patients with lupus nephritis, and associates with proteinuria severity, suggesting that it may have biomarker potential.[50]
# Interactions
ANKRD1 has been shown to interact with:
- Titin,[51]
- MYPN,[51][52]
- YBX1,[8]
- CASQ2,[53]
- DES,[5]
- TP53,[17]
- TLN1,[36] and
- FHL2.[36] | https://www.wikidoc.org/index.php/ANKRD1 | |
3efe74ad835c28461e7d8e8414d87eab45deec16 | wikidoc | ANKRD2 | ANKRD2
Ankyrin Repeat, PEST sequence and Proline-rich region (ARPP), also known as Ankyrin repeat domain-containing protein 2 is a protein that in humans is encoded by the ANKRD2 gene. ARPP is a member of the muscle ankyrin repeat proteins (MARP), which also includes CARP and DARP, and is highly expressed in cardiac and skeletal muscle and in other tissues. Expression of AARP has been shown to be altered in patients with dilated cardiomyopathy and amyotrophic lateral sclerosis.
# Structure
Two isoforms of ARPP have been documented; a 39.8 kDa protein isoform composed of 360 amino acids and a 36.2 kDa protein isoform composed of 327 amino acids. ANKRD2 has nine exons, four of which encode ankyrin repeats in the middle region of the protein, a PEST-like and Lysine-rich sequence in the N-terminal region, and a Proline-rich sequence containing consensus sequences for phosphorylation in the C-terminal region. It has been proposed that AARP can homo- or hetero-dimerize with other MARPs in an antiparallel fashion. ARPP is highly expressed in nuclei and I-bands in slow skeletal fibers and cardiac muscle, specifically in ventricular regions at intercalated discs; and expression in brain, pancreas and esophageal epithelium has also been documented. Though AARP and CARP proteins show significant homology, their expression profiles in muscle cells are markedly different; CARP is expressed throughout atria and ventricles, in development and in adult myocytes, however AARP is almost exclusively ventricular and only in adult myocytes. AARP was also found to be expressed in rhabdomyosarcomas, exhibiting a pattern distinct from actin and desmin.
# Function
AARP localizes to both nuclei and sarcomeres in muscle cells. ARPP may play a role in the differentiation of myocytes, as ARPP expression was shown to be induced during the C2C12 differentiation in vitro. A role for AARP in regulating muscle gene expression and sensing stress signals was implicated in the finding that AARP colocalizes with the transcriptional co-activator and co-repressor PML in myoblast nuclei, and binds p53 to enhance the p21(WAFI/CIPI) promoter. It was further demonstrated that Nkx2.5 and p53 synergistically activate the ANKRD2 promoter to promote effects on myogenic differentiation. At the sarcomere, AARP binds titin at I-bands, which is potentiated by homo-dimerization and can alter the protein kinase A/protein kinase C phosphorylation status of itself or titin. These studies demonstrate a stretch-responsive relationship between AARP and Titin, which can be rapidly altered by post-translational mechanisms.
Functional insights into AARP function have come from transgenic studies. In mice lacking all three muscle ankyrin repeat proteins (MARPs), AARP, CARP, and DARP), skeletal muscles tended towards a more slower fiber type distribution, with longer resting sarcomere length, decreased fiber stiffness, expression of a longer titin isoform, greater degree of torque loss following eccentric contraction-related injury, and enhanced expression of MyoD and MLP. These findings suggest that AARP and related MARP proteins may play a role in the passive stiffness and gene regulatory roles in skeletal muscle. A study investigating AARP function in cardiac muscle in which AARP was knocked out alone or in combination with the other MARPs showed that mice displayed normal cardiac function at baseline and in response to pressure overload-induced cardiac hypertrophy, suggesting that these proteins are not essential for normal cardiac development or in response to a hypertrophic stimulus.
AARP has also shown to play a role in models of disease. AARP has also exhibited elevated expression following skeletal muscle denervation, persisting for four weeks following the insult. AARP (ANKRD2) gene expression was also shown to be rapidly induced in a model of eccentric contraction-related injury, showing peak expression (6-11 times normal value) within 12–24 hours following injury, suggesting that AARP may play a role in repair. In a mouse model of muscular dystrophy with myositis (mdm) caused by a small deletion in titin, ANKRD2 mRNA expression was shown to be significantly elevated in skeletal muscle tissue along with that of CARP, suggesting a role for AARP in titin-based signaling. Levels of AARP were also altered in a mouse model of diabetes.
# Clinical Significance
In patients with dilated cardiomyopathy, levels of AARP were upregulated.
AARP expression patterns have been shown to be altered in patients with amyotrophic lateral sclerosis (ALS), with decreased expression in slow skeletal muscle fibers and increased expression in fast skeletal muscle fibers.
ARPP has also been shown to be a potentially useful biomarker for the differential diagnosis between oncocytoma and chromophobe renal cell carcinomas.
In non-pathologic physiology, AARP mRNA expression in skeletal muscle of patients was shown to be elevated two days following fatiguing jumping exercises. Levels of CARP, MLP and calpain-2 mRNA levels were also enhanced, suggesting that these molecules may be part of a signaling network activated by physical exercise.
# Interactions
ANKRD2 has been shown to interact with
- Titin
- YBX1,
- TCAP,
- PML and
- TP53.
- Akt, | ANKRD2
Ankyrin Repeat, PEST sequence and Proline-rich region (ARPP), also known as Ankyrin repeat domain-containing protein 2 is a protein that in humans is encoded by the ANKRD2 gene.[1][2][3][4] ARPP is a member of the muscle ankyrin repeat proteins (MARP), which also includes CARP and DARP, and is highly expressed in cardiac and skeletal muscle and in other tissues. Expression of AARP has been shown to be altered in patients with dilated cardiomyopathy and amyotrophic lateral sclerosis.
# Structure
Two isoforms of ARPP have been documented; a 39.8 kDa protein isoform composed of 360 amino acids[5] and a 36.2 kDa protein isoform composed of 327 amino acids.[6] ANKRD2 has nine exons, four of which encode ankyrin repeats in the middle region of the protein, a PEST-like and Lysine-rich sequence in the N-terminal region, and a Proline-rich sequence containing consensus sequences for phosphorylation in the C-terminal region.[7][8] It has been proposed that AARP can homo- or hetero-dimerize with other MARPs in an antiparallel fashion.[9] ARPP is highly expressed in nuclei and I-bands in slow skeletal fibers[7][10] and cardiac muscle, specifically in ventricular regions[8] at intercalated discs;[11] and expression in brain, pancreas and esophageal epithelium has also been documented.[10][12] Though AARP and CARP proteins show significant homology, their expression profiles in muscle cells are markedly different; CARP is expressed throughout atria and ventricles, in development and in adult myocytes, however AARP is almost exclusively ventricular and only in adult myocytes. AARP was also found to be expressed in rhabdomyosarcomas, exhibiting a pattern distinct from actin and desmin.[13]
# Function
AARP localizes to both nuclei and sarcomeres in muscle cells. ARPP may play a role in the differentiation of myocytes, as ARPP expression was shown to be induced during the C2C12 differentiation in vitro.[13] A role for AARP in regulating muscle gene expression and sensing stress signals was implicated in the finding that AARP colocalizes with the transcriptional co-activator and co-repressor PML in myoblast nuclei, and binds p53 to enhance the p21(WAFI/CIPI) promoter.[14] It was further demonstrated that Nkx2.5 and p53 synergistically activate the ANKRD2 promoter to promote effects on myogenic differentiation.[15] At the sarcomere, AARP binds titin at I-bands, which is potentiated by homo-dimerization and can alter the protein kinase A/protein kinase C phosphorylation status of itself or titin.[9] These studies demonstrate a stretch-responsive relationship between AARP and Titin, which can be rapidly altered by post-translational mechanisms.
Functional insights into AARP function have come from transgenic studies. In mice lacking all three muscle ankyrin repeat proteins (MARPs), AARP, CARP, and DARP), skeletal muscles tended towards a more slower fiber type distribution, with longer resting sarcomere length, decreased fiber stiffness, expression of a longer titin isoform, greater degree of torque loss following eccentric contraction-related injury, and enhanced expression of MyoD and MLP. These findings suggest that AARP and related MARP proteins may play a role in the passive stiffness and gene regulatory roles in skeletal muscle.[16] A study investigating AARP function in cardiac muscle in which AARP was knocked out alone or in combination with the other MARPs showed that mice displayed normal cardiac function at baseline and in response to pressure overload-induced cardiac hypertrophy, suggesting that these proteins are not essential for normal cardiac development or in response to a hypertrophic stimulus.[17]
AARP has also shown to play a role in models of disease. AARP has also exhibited elevated expression following skeletal muscle denervation, persisting for four weeks following the insult.[10] AARP (ANKRD2) gene expression was also shown to be rapidly induced in a model of eccentric contraction-related injury, showing peak expression (6-11 times normal value) within 12–24 hours following injury, suggesting that AARP may play a role in repair.[18] In a mouse model of muscular dystrophy with myositis (mdm) caused by a small deletion in titin, ANKRD2 mRNA expression was shown to be significantly elevated in skeletal muscle tissue along with that of CARP, suggesting a role for AARP in titin-based signaling.[19] Levels of AARP were also altered in a mouse model of diabetes.[20]
# Clinical Significance
In patients with dilated cardiomyopathy, levels of AARP were upregulated.[21]
AARP expression patterns have been shown to be altered in patients with amyotrophic lateral sclerosis (ALS), with decreased expression in slow skeletal muscle fibers and increased expression in fast skeletal muscle fibers.[22]
ARPP has also been shown to be a potentially useful biomarker for the differential diagnosis between oncocytoma and chromophobe renal cell carcinomas.[23]
In non-pathologic physiology, AARP mRNA expression in skeletal muscle of patients was shown to be elevated two days following fatiguing jumping exercises. Levels of CARP, MLP and calpain-2 mRNA levels were also enhanced, suggesting that these molecules may be part of a signaling network activated by physical exercise.[24]
# Interactions
ANKRD2 has been shown to interact with
- Titin[25]
- YBX1,[2]
- TCAP,[2]
- PML[2] and
- TP53.[2]
- Akt,[26] | https://www.wikidoc.org/index.php/ANKRD2 | |
ca7923a34ab793b7b063dc1ee77032d636abab92 | wikidoc | ANKS1A | ANKS1A
Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A), also known as ODIN, is a protein that in humans is encoded by the ANKS1A gene on chromosome 6.
It is ubiquitously expressed in many tissues and cell types. ODIN is known to regulate the epidermal growth factor receptor (EGFR) and EphA receptor signaling pathways. As a Src family kinase target, ODIN has been implicated in the development of cancer. The ANKS1A gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.
# Structure
## Gene
The ANKS1A gene resides on chromosome 6 at the band 6p21.31 and includes 29 exons. This gene produces 2 isoforms through alternative splicing.
## Protein
ODIN is a member of the ankyrin repeat and sterile alpha motif domain-containing (ANKS) family and contains 6 ankyrin repeats, 1 phosphotyrosine binding (PTD) domain, and 2 tandem sterile alpha motif (SAM) domains. The first SAM domain binds to the SAM domain of the EphA2 receptor by adopting a mid-loop/end-helix conformation and may regulate EphA2 endocytosis.
# Function
ODIN is widely expressed in tissues including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. ODIN has been identified as one of the tyrosine phosphorylated proteins induced by activating epidermal growth factor or platelet-derived growth factor receptor tyrosine kinases. ODIN is involved in negative regulation of the EGFR signaling pathway. It is reported that ODIN level is correlated with the degree of increased EGF-induced EGFR trafficking to recycle endosomes and recycle back to the cell surface, suggesting a role in EGFR recycling. Furthermore, ODIN serves as a key adaptor protein regulating the EphA receptor signaling pathway, which is critical for regulating EphA8-mediated cell migration and neurite outgrowth. It has been demonstrated that deletion of the phosphotyrosine binding domain in ODIN will lead to an immaturely developed subcommissural organ (SCO) with a severe midbrain hydrocephalic phenotype, which means ODIN also plays a role in the proper development of the SCO and in ependymal cells in the cerebral aqueduct.
# Clinical significance
As a novel target of Src family kinases, which are implicated in the development of some colorectal cancers, ODIN may be involved in cancer cell signaling mechanisms. In a study, 64 colorectal cancer cell lines were tested for their expression of Lck. Mass spectrometric analyses of Lck-purified proteins subsequently identified several proteins readily known as SFK kinase substrates, including cortactin, Tom1L1 (SRCASM), GIT1, vimentin and AFAP1L2 (XB130). Additional proteins previously reported as substrates of other tyrosine kinases were also detected, including ODIN. ODIN was further analyzed and found to contain substantially less pY upon inhibition of SFK activity in SW620 cells, indicating that it is a formerly unknown SFK target in colorectal carcinoma cells. Furthermore, it has been found that ODIN regulates COPII-mediated anterograde transport of receptor tyrosine kinases, which is a critical mechanism in the process of tumor genesis.
## Clinical marker
A multi-locus genetic risk score study based on a combination of 27 loci, including the ANKS1A gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22). | ANKS1A
Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A), also known as ODIN, is a protein that in humans is encoded by the ANKS1A gene on chromosome 6.[1][2]
It is ubiquitously expressed in many tissues and cell types.[3] ODIN is known to regulate the epidermal growth factor receptor (EGFR) and EphA receptor signaling pathways.[4] As a Src family kinase target, ODIN has been implicated in the development of cancer.[5] The ANKS1A gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.[6]
# Structure
## Gene
The ANKS1A gene resides on chromosome 6 at the band 6p21.31 and includes 29 exons.[2] This gene produces 2 isoforms through alternative splicing.[7]
## Protein
ODIN is a member of the ankyrin repeat and sterile alpha motif domain-containing (ANKS) family and contains 6 ankyrin repeats, 1 phosphotyrosine binding (PTD) domain, and 2 tandem sterile alpha motif (SAM) domains.[7][8] The first SAM domain binds to the SAM domain of the EphA2 receptor by adopting a mid-loop/end-helix conformation and may regulate EphA2 endocytosis.[8][9]
# Function
ODIN is widely expressed in tissues including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.[10] ODIN has been identified as one of the tyrosine phosphorylated proteins induced by activating epidermal growth factor or platelet-derived growth factor receptor tyrosine kinases.[10] ODIN is involved in negative regulation of the EGFR signaling pathway.[4] It is reported that ODIN level is correlated with the degree of increased EGF-induced EGFR trafficking to recycle endosomes and recycle back to the cell surface, suggesting a role in EGFR recycling.[11] Furthermore, ODIN serves as a key adaptor protein regulating the EphA receptor signaling pathway, which is critical for regulating EphA8-mediated cell migration and neurite outgrowth.[12][13] It has been demonstrated that deletion of the phosphotyrosine binding domain in ODIN will lead to an immaturely developed subcommissural organ (SCO) with a severe midbrain hydrocephalic phenotype, which means ODIN also plays a role in the proper development of the SCO and in ependymal cells in the cerebral aqueduct.[14]
# Clinical significance
As a novel target of Src family kinases, which are implicated in the development of some colorectal cancers, ODIN may be involved in cancer cell signaling mechanisms.[15] In a study, 64 colorectal cancer cell lines were tested for their expression of Lck. Mass spectrometric analyses of Lck-purified proteins subsequently identified several proteins readily known as SFK kinase substrates, including cortactin, Tom1L1 (SRCASM), GIT1, vimentin and AFAP1L2 (XB130). Additional proteins previously reported as substrates of other tyrosine kinases were also detected, including ODIN. ODIN was further analyzed and found to contain substantially less pY upon inhibition of SFK activity in SW620 cells, indicating that it is a formerly unknown SFK target in colorectal carcinoma cells.[15] Furthermore, it has been found that ODIN regulates COPII-mediated anterograde transport of receptor tyrosine kinases, which is a critical mechanism in the process of tumor genesis.[16]
## Clinical marker
A multi-locus genetic risk score study based on a combination of 27 loci, including the ANKS1A gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).[6] | https://www.wikidoc.org/index.php/ANKS1A | |
f20ae4727a9c8a57644170ade742ddf1ed9c6166 | wikidoc | APPBP1 | APPBP1
NEDD8-activating enzyme E1 regulatory subunit is a protein that in humans is encoded by the NAE1 gene.
# Function
The protein encoded by this gene binds to the beta-amyloid precursor protein. Beta-amyloid precursor protein is a cell surface protein with signal-transducing properties, and it is thought to play a role in the pathogenesis of Alzheimer's disease. In addition, the encoded protein can form a heterodimer with UBE1C and bind and activate NEDD8, a ubiquitin-like protein. This protein is required for cell cycle progression through the S/M checkpoint. Three transcript variants encoding different isoforms have been found for this gene.
APPBP1 (Amyloid Precursor Protein-Binding Protein 1) binds to the Amyloid Precursor Protein (APP) carboxy terminal domain. APPBP1 is a multi-functional protein with activities in neuronal tissues. APPBP1 also bonds with UBA3 (ubiquitin-like protein-activating enzyme 3) to form the NEDD8 activating enzyme (NAE). Activated NEDD8 is an enzyme that regulates multiple cellular pathways.
# History
APPBP1 was first cloned and identified by its interaction with the C-terminus of beta-amyloid protein precursor (precursor to beta-amyloid present in Alzheimer's disease) in 1996. APPBP1 was first studied for its potential neuronal effects, and neuronal effects continue to be further investigated (e.g. references).
# Role in NEDD8 activation
APPBP1 can bind to UBA3 to form the NEDD8 activating enzyme (NAE) (homologous to the ubiquitin-activating enzymes, also known as E1 enzymes). When NEDD8 is activated it can neddylate (and thereby alter the activity of) target proteins. Neddylation has emerged as a major regulatory pathway with a critical role, among others, in cell cycle progression and survival. Proteins that are neddylated include the DNA replication licensing factor Cdt-1, the NF-κB transcription factor inhibitor pIκBα, and the cell cycle regulators cyclin E and p27. Thus, APPBP1 carries out an initiating step that controls major regulatory pathways in the cell.
The first step in activation of NEDD8 by NAE is the extensive interaction of the acidic face of NEDD8’s globular domain with the catalytic cysteine domain portion of the APPBP1 component of NAE. The interface between NEDD8 and APPBP1 involves the helix and subsequent loop in NEDD8 and a sub-domain comprising APPBP1’s residues 178–280 that serves as a wall for the broad, deep groove in the APPBP1-UBA3 structure. The nature of this interface is predominantly polar, with 11 residues from NEDD8 forming a network of hydrogen bonds and salt bridges with 9 residues from the APPBP1 component of NAE.
Subsequent activation steps were described by Walden et al., and Schulman. NEDD8 interacts with an adenylation pocket of the UBA3 part of the heterodimeric NAE to form covalently linked NEDD8-AMP. NEDD8 then forms a covalent thioester bond with a reactive cysteine of the UBA3 part of NAE. After this, a second NEDD8 is attracted to APPBP1 followed by adenylation in the UBA3 adenylation pocket. The activated NAE is thus loaded with two NEDD8 molecules asymmetrically arranged.
# Role in DNA repair
After activation of NEDD8, initiated by APPBP1, NEDD8 interaction at DNA-damage sites is a highly dynamic process. Neddylation is needed during a short period of the global genome repair (GGR) sub-pathway of DNA nucleotide excision repair (NER). When DNA damage is produced by UV irradiation, CUL4A in the DNA damage binding protein 2 (DDB2) complex is activated by NEDD8, and this activated complex allows GGR-NER to proceed to remove the damage.
Neddylation also has a role in repair of double-strand breaks. Non-homologous end joining(NHEJ) is a DNA repair pathway frequently used to repair DNA double-strand breaks. The first step in this pathway depends on the Ku70/Ku80 heterodimer that forms a highly stable ring structure encircling DNA ends. But the Ku heterodimer needs to be removed when NHEJ is completed, or it can block transcription or replication. The Ku heterodimer is ubiquitylated in a DNA-damage and neddylation-dependent manner to promote the release of Ku and other NHEJ factors from the site of repair after the process is completed.
# Role in cancer therapy
When APPBP1 complexes with UBA3 to form the NEDD8 activating enzyme (NAE), it changes the conformation of UBA3 from the free form to a form that can carry out the cascade of actions needed to activate NEDD8. The adenylation pocket of UBA3 in the hetero-dimeric NAE enzyme is critical for NEDD8 activation.
Pevonedistat (MLN4924) is an analog of adenosine sulfamate.
Pevonedistat is a mechanism-based inhibitor of NAE. NAE catalyzes formation of a covalent NEDD8-Pevonedistat adduct. The covalent NEDD8-Pevonedistat adduct occupies the same sites as ATP and NEDD8 bound in the adenylation active site in the NAE structure. The NEDD8-Pevonedistat adduct resembles NEDD8 adenylate, the first intermediate in the NAE reaction cycle, but cannot be further utilized in subsequent intraenzyme reactions. The stability of the NEDD8-Pevonedistat adduct within the NAE active site blocks enzyme activity, thereby accounting for the potent inhibition of the NEDD8 pathway by Pevonedistat.
As described above, activated NEDD8 is needed for at least two pathways of DNA repair, nucleotide excision repair (NER) and non-homologous end joining (NHEJ) (see NEDD8).
One or more DNA repair genes in seven DNA repair pathways are frequently epigenetically silenced in cancers (see e.g. DNA repair pathways).) This is a likely source of the genome instability of cancers. If activation of NEDD8 is inhibited by Pevonedistat, cancer cells will then have an additional induced deficiency of NER or NHEJ. Such cells may then die because of deficient DNA repair leading to accumulation of DNA damages. The effect of NEDD8 inhibition may be greater for cancer cells than for normal cells if the cancer cells are already deficient in DNA repair due to prior epigenetic silencing of DNA repair genes active in alternative pathways (see synthetic lethality).
# Clinical trials
In a phase 1 trial of Pevonedistat to determine dosing in patients with AML and myelodysplastic syndromes "modest clinical activity was observed".
More recently, in 2016, Pevonedistat has shown a significant therapeutic effect in three further Phase I clinical cancer trials. These include Pevonedistat trials against relapsed/refractory multiple myeloma or lymphoma, metastatic melanoma, and advanced solid tumors.
# Interactions
APPBP1 has been shown to interact with UBE1C, TRIP12 and Amyloid precursor protein. | APPBP1
NEDD8-activating enzyme E1 regulatory subunit is a protein that in humans is encoded by the NAE1 gene.[1][2][3]
# Function
The protein encoded by this gene binds to the beta-amyloid precursor protein. Beta-amyloid precursor protein is a cell surface protein with signal-transducing properties, and it is thought to play a role in the pathogenesis of Alzheimer's disease. In addition, the encoded protein can form a heterodimer with UBE1C and bind and activate NEDD8, a ubiquitin-like protein. This protein is required for cell cycle progression through the S/M checkpoint. Three transcript variants encoding different isoforms have been found for this gene.[3]
APPBP1 (Amyloid Precursor Protein-Binding Protein 1) binds to the Amyloid Precursor Protein (APP) carboxy terminal domain.[4] APPBP1 is a multi-functional protein with activities in neuronal tissues. APPBP1 also bonds with UBA3 (ubiquitin-like protein-activating enzyme 3[5]) to form the NEDD8 activating enzyme (NAE). Activated NEDD8 is an enzyme that regulates multiple cellular pathways.
# History
APPBP1 was first cloned and identified by its interaction with the C-terminus of beta-amyloid protein precursor (precursor to beta-amyloid present in Alzheimer's disease) in 1996.[1] APPBP1 was first studied for its potential neuronal effects, and neuronal effects continue to be further investigated (e.g. references[6][7]).
# Role in NEDD8 activation
APPBP1 can bind to UBA3 to form the NEDD8 activating enzyme (NAE) (homologous to the ubiquitin-activating enzymes, also known as E1 enzymes). When NEDD8 is activated it can neddylate (and thereby alter the activity of) target proteins. Neddylation has emerged as a major regulatory pathway with a critical role, among others, in cell cycle progression and survival. Proteins that are neddylated include the DNA replication licensing factor Cdt-1, the NF-κB transcription factor inhibitor pIκBα, and the cell cycle regulators cyclin E and p27.[8] Thus, APPBP1 carries out an initiating step that controls major regulatory pathways in the cell.
The first step in activation of NEDD8 by NAE is the extensive interaction of the acidic face of NEDD8’s globular domain with the catalytic cysteine domain portion of the APPBP1 component of NAE.[9] The interface between NEDD8 and APPBP1 involves the helix and subsequent loop in NEDD8 and a sub-domain comprising APPBP1’s residues 178–280 that serves as a wall for the broad, deep groove in the APPBP1-UBA3 structure. The nature of this interface is predominantly polar, with 11 residues from NEDD8 forming a network of hydrogen bonds and salt bridges with 9 residues from the APPBP1 component of NAE.
Subsequent activation steps were described by Walden et al.,[9] and Schulman.[10] NEDD8 interacts with an adenylation pocket of the UBA3 part of the heterodimeric NAE to form covalently linked NEDD8-AMP. NEDD8 then forms a covalent thioester bond with a reactive cysteine of the UBA3 part of NAE. After this, a second NEDD8 is attracted to APPBP1 followed by adenylation in the UBA3 adenylation pocket. The activated NAE is thus loaded with two NEDD8 molecules asymmetrically arranged.
# Role in DNA repair
After activation of NEDD8, initiated by APPBP1, NEDD8 interaction at DNA-damage sites is a highly dynamic process.[11] Neddylation is needed during a short period of the global genome repair (GGR) sub-pathway of DNA nucleotide excision repair (NER). When DNA damage is produced by UV irradiation, CUL4A in the DNA damage binding protein 2 (DDB2) complex is activated by NEDD8, and this activated complex allows GGR-NER to proceed to remove the damage.[12]
Neddylation also has a role in repair of double-strand breaks.[11] Non-homologous end joining(NHEJ) is a DNA repair pathway frequently used to repair DNA double-strand breaks. The first step in this pathway depends on the Ku70/Ku80 heterodimer that forms a highly stable ring structure encircling DNA ends.[13] But the Ku heterodimer needs to be removed when NHEJ is completed, or it can block transcription or replication. The Ku heterodimer is ubiquitylated in a DNA-damage and neddylation-dependent manner to promote the release of Ku and other NHEJ factors from the site of repair after the process is completed.[11]
# Role in cancer therapy
When APPBP1 complexes with UBA3 to form the NEDD8 activating enzyme (NAE), it changes the conformation of UBA3 from the free form to a form that can carry out the cascade of actions needed to activate NEDD8.[9] The adenylation pocket of UBA3 in the hetero-dimeric NAE enzyme is critical for NEDD8 activation.
Pevonedistat (MLN4924) is an analog of adenosine sulfamate.[14]
Pevonedistat is a mechanism-based inhibitor of NAE. NAE catalyzes formation of a covalent NEDD8-Pevonedistat adduct. The covalent NEDD8-Pevonedistat adduct occupies the same sites as ATP and NEDD8 bound in the adenylation active site in the NAE structure.[14] The NEDD8-Pevonedistat adduct resembles NEDD8 adenylate, the first intermediate in the NAE reaction cycle, but cannot be further utilized in subsequent intraenzyme reactions. The stability of the NEDD8-Pevonedistat adduct within the NAE active site blocks enzyme activity, thereby accounting for the potent inhibition of the NEDD8 pathway by Pevonedistat.
As described above, activated NEDD8 is needed for at least two pathways of DNA repair, nucleotide excision repair (NER) and non-homologous end joining (NHEJ) (see NEDD8).
One or more DNA repair genes in seven DNA repair pathways are frequently epigenetically silenced in cancers (see e.g. DNA repair pathways).[15][16]) This is a likely source of the genome instability of cancers. If activation of NEDD8 is inhibited by Pevonedistat, cancer cells will then have an additional induced deficiency of NER or NHEJ. Such cells may then die because of deficient DNA repair leading to accumulation of DNA damages. The effect of NEDD8 inhibition may be greater for cancer cells than for normal cells if the cancer cells are already deficient in DNA repair due to prior epigenetic silencing of DNA repair genes active in alternative pathways (see synthetic lethality).
# Clinical trials
In a phase 1 trial of Pevonedistat to determine dosing in patients with AML and myelodysplastic syndromes "modest clinical activity was observed".[17]
More recently, in 2016, Pevonedistat has shown a significant therapeutic effect in three further Phase I clinical cancer trials. These include Pevonedistat trials against relapsed/refractory multiple myeloma or lymphoma,[18] metastatic melanoma,[19] and advanced solid tumors.[20]
# Interactions
APPBP1 has been shown to interact with UBE1C,[21] TRIP12[22] and Amyloid precursor protein.[1] | https://www.wikidoc.org/index.php/APPBP1 | |
bb4e835167c52968afc8a71a05b750ab666de184 | wikidoc | ARGLU1 | ARGLU1
Arginine and glutamate-rich protein 1 is a protein that in humans is encoded by the ARGLU1 gene located at 13q33.3.
The protein product of this gene has been proposed as a MED1-interacting protein required for estrogen-dependent gene transcription and breast cancer cell growth.
The ARGLU1 gene expresses at least three distinct RNA splice isoforms - a fully spliced isoform coding for the protein, an isoform containing a retained intron that is detained in the nucleus, and an isoform containing an alternative exon that targets the transcript for nonsense mediated decay. Furthermore, ARGLU1 contains a long, highly evolutionarily conserved sequence known as an Ultraconserved Element (UCE) that is within the retained intron and overlaps the alternative exon. | ARGLU1
Arginine and glutamate-rich protein 1 is a protein that in humans is encoded by the ARGLU1 gene located at 13q33.3.[1]
The protein product of this gene has been proposed as a MED1-interacting protein required for estrogen-dependent gene transcription and breast cancer cell growth.[2]
The ARGLU1 gene expresses at least three distinct RNA splice isoforms - a fully spliced isoform coding for the protein, an isoform containing a retained intron that is detained in the nucleus, and an isoform containing an alternative exon that targets the transcript for nonsense mediated decay. Furthermore, ARGLU1 contains a long, highly evolutionarily conserved sequence known as an Ultraconserved Element (UCE) that is within the retained intron and overlaps the alternative exon. [3] | https://www.wikidoc.org/index.php/ARGLU1 | |
20a485a75f3e7c0d6632ded021898d4872f724c3 | wikidoc | ARID1A | ARID1A
AT-rich interactive domain-containing protein 1A is a protein that in humans is encoded by the ARID1A gene.
# Function
ARID1A is a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. It possesses at least two conserved domains that could be important for its function. First, it has an ARID domain, which is a DNA-binding domain that can specifically bind an AT-rich DNA sequence known to be recognized by a SWI/SNF complex at the beta-globin locus. Second, the C-terminus of the protein can stimulate glucocorticoid receptor-dependent transcriptional activation. It is thought that the protein encoded by this gene confers specificity to the SWI/SNF complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions. Two transcript variants encoding different isoforms have been found for this gene.
# Clinical significance
This gene has been commonly found mutated in gastric cancers, ovarian clear cell carcinoma, and pancreatic cancer.
In breast cancer distant metastases acquire inactivation mutations in ARID1A not seen in the primary tumor, and reduced ARID1A expression confers resistance to different drugs such as trastuzumab and mTOR inhibitors. these findings provide a rationale for why tumors accumulate ARID1A mutations.
# Research
Lack of this gene/protein seems to protect rats from some types of liver damage.
# Interactions
ARID1A has been shown to interact with SMARCB1 and SMARCA4. | ARID1A
AT-rich interactive domain-containing protein 1A is a protein that in humans is encoded by the ARID1A gene.[1][2][3]
# Function
ARID1A is a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. It possesses at least two conserved domains that could be important for its function. First, it has an ARID domain, which is a DNA-binding domain that can specifically bind an AT-rich DNA sequence known to be recognized by a SWI/SNF complex at the beta-globin locus. Second, the C-terminus of the protein can stimulate glucocorticoid receptor-dependent transcriptional activation. It is thought that the protein encoded by this gene confers specificity to the SWI/SNF complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions. Two transcript variants encoding different isoforms have been found for this gene.[3]
# Clinical significance
This gene has been commonly found mutated in gastric cancers,[4] ovarian clear cell carcinoma,[5] and pancreatic cancer.[6]
In breast cancer distant metastases acquire inactivation mutations in ARID1A not seen in the primary tumor, and reduced ARID1A expression confers resistance to different drugs such as trastuzumab and mTOR inhibitors. these findings provide a rationale for why tumors accumulate ARID1A mutations. [7] [8]
# Research
Lack of this gene/protein seems to protect rats from some types of liver damage.[9]
# Interactions
ARID1A has been shown to interact with SMARCB1[10][11] and SMARCA4.[11][12] | https://www.wikidoc.org/index.php/ARID1A | |
130e8bd17b6def60a0368ee6589983dab31b0a35 | wikidoc | ARID4A | ARID4A
AT rich interactive domain 4A (RBP1-like), also known as ARID4A, is a protein which in humans is encoded by the ARID4A gene.
# Function
The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblastoma protein (pRB) which regulates cell proliferation. pRB represses transcription by recruiting the encoded protein. This protein, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function. The encoded protein possesses transcriptional repression activity. Multiple alternatively spliced transcripts have been observed for this gene, although not all transcript variants have been fully described.
# Model organisms
Model organisms have been used in the study of ARID4A function. A conditional knockout mouse line, called Arid4atm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.
Twenty five tests were carried out and nine phenotypes were reported. Fewer homozygous mutant embryos were identified during gestation than expected, and in a separate study less than the predicted Mendelian ratio survived until weaning. Homozygous mutant male adults has a reduced body weight curve and a decreased grip strength. Homozygous mutant adults of both sexes had a decreased body weight as determined by DEXA, displayed vertebral fusion and had clinical chemistry abnormalities including hypoalbuminemia and decreased circulating fructosamine levels. They also had haematological defects and an increased NK cell number.
# Interactions
ARID4A has been shown to interact with Retinoblastoma protein. | ARID4A
AT rich interactive domain 4A (RBP1-like), also known as ARID4A, is a protein which in humans is encoded by the ARID4A gene.[1][2][3]
# Function
The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblastoma protein (pRB) which regulates cell proliferation. pRB represses transcription by recruiting the encoded protein. This protein, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function. The encoded protein possesses transcriptional repression activity. Multiple alternatively spliced transcripts have been observed for this gene, although not all transcript variants have been fully described.[1]
# Model organisms
Model organisms have been used in the study of ARID4A function. A conditional knockout mouse line, called Arid4atm1a(EUCOMM)Wtsi[14][15] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[16][17][18] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19]
Twenty five tests were carried out and nine phenotypes were reported. Fewer homozygous mutant embryos were identified during gestation than expected, and in a separate study less than the predicted Mendelian ratio survived until weaning. Homozygous mutant male adults has a reduced body weight curve and a decreased grip strength. Homozygous mutant adults of both sexes had a decreased body weight as determined by DEXA, displayed vertebral fusion and had clinical chemistry abnormalities including hypoalbuminemia and decreased circulating fructosamine levels. They also had haematological defects and an increased NK cell number.[12]
# Interactions
ARID4A has been shown to interact with Retinoblastoma protein.[20] | https://www.wikidoc.org/index.php/ARID4A | |
9573590aed1eaf760bfcec44ca0446c736e26810 | wikidoc | ARID5B | ARID5B
AT-rich interactive domain-containing protein 5B is a protein that in humans is encoded by the ARID5B gene.
Alternative names for this gene include Modulator recognition factor 23.
# Genomics
The gene is located on the long arm of chromosome 10 (10q21.2) on the Watson (plus) strand. It spans 195,261 base pairs in length. It encodes a protein of predicted length and molecular weight of 1188 amino acids and 132.375 kilo Daltons respectively.
# Clinical importance
Through genome wide association studies (GWAS),some of the single nucleotide polymorphisms (SNPs) located in this gene has been noticed to be significantly associated with susceptibility
as well as treatment outcomes of childhood acute lymphoblastic leukaemia in ethnically diverse populations. | ARID5B
AT-rich interactive domain-containing protein 5B is a protein that in humans is encoded by the ARID5B gene.[1][2][3]
Alternative names for this gene include Modulator recognition factor 23.
# Genomics
The gene is located on the long arm of chromosome 10 (10q21.2) on the Watson (plus) strand. It spans 195,261 base pairs in length. It encodes a protein of predicted length and molecular weight of 1188 amino acids and 132.375 kilo Daltons respectively.
# Clinical importance
Through genome wide association studies (GWAS),some of the single nucleotide polymorphisms (SNPs) located in this gene has been noticed to be significantly associated with susceptibility [4][5][6]
as well as treatment outcomes [7] of childhood acute lymphoblastic leukaemia in ethnically diverse populations. | https://www.wikidoc.org/index.php/ARID5B | |
c7019ed5972f94522f11fd53c6fbd8fc0219f909 | wikidoc | ARL13B | ARL13B
ADP-ribosylation factor-like protein 13B (ARL13B), also known as ADP-ribosylation factor-like protein 2-like 1, is a protein that in humans is encoded by the ARL13B gene.
# Function
This gene encodes a member of the ADP-ribosylation factor-like family. The encoded protein is a small GTPase that contains both N-terminal and C-terminal guanine nucleotide-binding motifs. This protein is localized in the cilia and plays a role in cilia formation and in maintenance of cilia.
# Clinical significance
Mutations in the ARL13B gene are associated with the Joubert syndrome. | ARL13B
ADP-ribosylation factor-like protein 13B (ARL13B), also known as ADP-ribosylation factor-like protein 2-like 1, is a protein that in humans is encoded by the ARL13B gene.[1][2]
# Function
This gene encodes a member of the ADP-ribosylation factor-like family. The encoded protein is a small GTPase that contains both N-terminal and C-terminal guanine nucleotide-binding motifs. This protein is localized in the cilia[3][4] and plays a role in cilia formation and in maintenance of cilia.[1]
# Clinical significance
Mutations in the ARL13B gene are associated with the Joubert syndrome.[2] | https://www.wikidoc.org/index.php/ARL13B | |
50dd21ce6f8746e348833f2dd50b806b84d7c8d9 | wikidoc | ARMCX5 | ARMCX5
ARMCX5 is an armadillo repeat–containing protein that is encoded by the X-linked ARMCX5 gene. It is conserved only in Eutheria, a specific group of placental mammals, but no further back in evolutionary time. ARMCX5 contains 3 ARM-like repeats, DUF364, and ARM-type fold.
# Features
# Splice Variants
ARMCX5 has 6 splice variants.
# ORTHOLOGS
ARMCX5 has ten orthologs.
# Paralogs
ARMCX5 has 8 paralogs listed by genecards: GPRASP2, ARMCX1, BHLHB9, ARMCX2, GPRASP1, ARMCX6, ARMCX10, and ARMCX3.
# Function
Proteins containing this ARMCX5 domain interact with numerous other proteins. Through these interactions, they are involved in a wide variety of processes including carcinogenesis, control of cellular ageing and survival, regulation f circadian rhythm and lysosomal sorting of G-protein coupled receptors.
Because DUF364 contains a PLP-dependent transferase-like fold, the genomic context suggests that it may have a role in anaerobic vitamin B12 biosynthesis.
# Expression
ARMCX5 is a highly ubiquitously expressed gene that has shown expression in many tissues. | ARMCX5
ARMCX5 is an armadillo repeat–containing protein that is encoded by the X-linked ARMCX5 gene. It is conserved only in Eutheria,[1] a specific group of placental mammals, but no further back in evolutionary time. ARMCX5 contains 3 ARM-like repeats, DUF364, and ARM-type fold.[2]
# Features
[3]
# Splice Variants
ARMCX5 has 6 splice variants.
[3]
# ORTHOLOGS
ARMCX5 has ten orthologs.
[4]
# Paralogs
ARMCX5 has 8 paralogs listed by genecards: GPRASP2, ARMCX1, BHLHB9, ARMCX2, GPRASP1, ARMCX6, ARMCX10, and ARMCX3.[2]
# Function
Proteins containing this ARMCX5 domain interact with numerous other proteins. Through these interactions, they are involved in a wide variety of processes including carcinogenesis, control of cellular ageing and survival, regulation f circadian rhythm and lysosomal sorting of G-protein coupled receptors.[2]
Because DUF364 contains a PLP-dependent transferase-like fold, the genomic context suggests that it may have a role in anaerobic vitamin B12 biosynthesis.[5]
# Expression
ARMCX5 is a highly ubiquitously expressed gene that has shown expression in many tissues.
[6] | https://www.wikidoc.org/index.php/ARMCX5 | |
2ee775bf253e2981c2aed70d1f8079be4f833abd | wikidoc | ARMCX6 | ARMCX6
Armadillo repeat containing X-linked 6 is a protein that in humans is encoded by the ARMCX6 gene located on the X-chromosome.
It is one of six armadillo repeats containing X-linked proteins (ARMCX1, ARMCX2, ARMCX3, ARMCX4, ARMCX5, and ARMCX6 (this protein)).
The function of this protein is unknown at this time.
# Protein sequence
# Homology
ARMCX6 is conserved in many eukaryotic organisms.
# Orthologs
## Secondary Structure
The secondary structure of ARMCX6 is predicted to be similar to cyanase. A comparison of the two sequences is shown below.
# Expression
Microarray data show that ARMCX6 is highly expressed during earliest stages of spermatogenesis in mice. | ARMCX6
Armadillo repeat containing X-linked 6 is a protein that in humans is encoded by the ARMCX6 gene located on the X-chromosome.[1]
It is one of six armadillo repeats containing X-linked proteins (ARMCX1, ARMCX2, ARMCX3, ARMCX4, ARMCX5, and ARMCX6 (this protein)).
The function of this protein is unknown at this time.
# Protein sequence
# Homology
ARMCX6 is conserved in many eukaryotic organisms.
# Orthologs
## Secondary Structure
The secondary structure of ARMCX6 is predicted to be similar to cyanase. A comparison of the two sequences is shown below.[2][3]
# Expression
Microarray data show that ARMCX6 is highly expressed during earliest stages of spermatogenesis in mice.[4][5][6] | https://www.wikidoc.org/index.php/ARMCX6 | |
c51ea7a1f04227d6262e9233ccf47c0793ccac25 | wikidoc | ARNTL2 | ARNTL2
Aryl hydrocarbon receptor nuclear translocator-like 2, also known as Mop9, Bmal2, Clif, or Arntl2, is a gene.
Arntl2 is a paralog to Arntl, which are both homologs of the Drosophila Cycle. Homologs were also isolated in fish, birds and mammals such as mice and humans. Based on phylogenetic analyses, it was proposed that Arntl2 arose from duplication of the Arntl gene early in the vertebrate lineage, followed by rapid divergence of the Arntl gene copy. The protein product of the gene interacts with both CLOCK and NPAS2 to bind to E-box sequences in regulated promoters and activate their transcription. Although Arntl2 is not required for normal function of the mammalian circadian oscillator, it may play an important role in mediating the output of the circadian clock. Perhaps because of this, there is relatively little published literature on the role of Arntl2 in regulation of physiology.
Arntl2 is a candidate gene for human type 1 diabetes.
In over expression studies, ARNTL2 protein forms a heterodimer with CLOCK to regulate E-box sequences in the Pai-1 promoter. Recent work suggest that this interaction may be in concert with ARNTL/CLOCK heterodimeric complexes. | ARNTL2
Aryl hydrocarbon receptor nuclear translocator-like 2, also known as Mop9,[1] Bmal2,[2] Clif,[3] or Arntl2, is a gene.
Arntl2 is a paralog to Arntl, which are both homologs of the Drosophila Cycle.[4] Homologs were also isolated in fish,[5] birds[6] and mammals such as mice[7] and humans.[1] Based on phylogenetic analyses, it was proposed that Arntl2 arose from duplication of the Arntl gene early in the vertebrate lineage, followed by rapid divergence of the Arntl gene copy.[7] The protein product of the gene interacts with both CLOCK and NPAS2 to bind to E-box sequences in regulated promoters and activate their transcription.[1] Although Arntl2 is not required for normal function of the mammalian circadian oscillator, it may play an important role in mediating the output of the circadian clock. Perhaps because of this, there is relatively little published literature on the role of Arntl2 in regulation of physiology.
Arntl2 is a candidate gene for human type 1 diabetes.[8]
In over expression studies, ARNTL2 protein forms a heterodimer with CLOCK to regulate E-box sequences in the Pai-1 promoter.[3] Recent work suggest that this interaction may be in concert with ARNTL/CLOCK heterodimeric complexes.[9] | https://www.wikidoc.org/index.php/ARNTL2 | |
3071d78d72fd70709541e60f0f38db572163b132 | wikidoc | ARTS-1 | ARTS-1
Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator, also known as endoplasmic reticulum aminopeptidase 1 (ARTS-1), is a protein which in humans is encoded by the ARTS-1 gene.
Endoplasmic reticulum amino peptidase 1 is active in the endoplasmic reticulum, which is involved in protein processing and transport. This protein is an aminopeptidase, which is an enzyme that cleaves other proteins into smaller fragments called peptides.
# Nomenclature
ARTS1 is also known as:
- ER aminopeptidase 1 (ERAP1) the name accepted by the Hugo Gene Nomenclature Committee
- ER aminopeptidase associated with antigen processing (ERAAP)
- Adipocyte-derived leucine aminopeptidase (ALAP)
- Puromycin-insensitive leucine aminopeptidase (PILS-AP)
# Function
ERAP1 has two major functions in the immune system:
- First, ERAP1 cleaves several proteins called cytokine receptors on the surface of cells. Cleaving these receptors reduces their ability to transmit chemical signals into the cell, which affects the process of inflammation.
- Second, ERAP1 trims peptides within the endoplasmic reticulum so that they can be loaded onto major histocompatibility complex (MHC) class I. These peptides are attached to MHC class I in the endoplasmic reticulum and exported to the cell surface, where they are displayed to the immune system. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it responds by triggering the infected cell to self-destruct.
ARTS-1 is a member of the M1 family of zinc metallopeptidases which acts as an aminopeptidase that degrades oligopeptides by cleavage starting at the amino terminus. One of the functions of aminopeptidases is to degrade potentially toxic peptides in the cytosol.
ARTS-1 is a transmembrane protein that is localized to the endoplasmic reticulum. It has been implicated in the following functions:
- Shedding of various cytokine receptors and decoy receptors
- Trimming of antigenic peptides before binding to MHC class I, affecting antigen presentation to cytotoxic T lymphocytes
# Clinical significance
Aminopeptidases play a role in the metabolism of several peptides that may be involved in blood pressure and the pathogenesis of essential hypertension. Mutations in the ARTS-1 have been linked to an increased risk of ankylosing spondylitis but only in HLA-B27 positive patients .
The protein encoded by this gene is an aminopeptidase involved in trimming HLA class I-binding precursors so that they can be presented on MHC class I molecules. The encoded protein acts as a monomer or as a heterodimer with ERAP2. This protein may also be involved in blood pressure regulation by inactivation of angiotensin II. Three transcript variants encoding two different isoforms have been found for this gene. | ARTS-1
Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator, also known as endoplasmic reticulum aminopeptidase 1 (ARTS-1), is a protein which in humans is encoded by the ARTS-1 gene.[1]
Endoplasmic reticulum amino peptidase 1 is active in the endoplasmic reticulum, which is involved in protein processing and transport. This protein is an aminopeptidase, which is an enzyme that cleaves other proteins into smaller fragments called peptides.
# Nomenclature
ARTS1 is also known as:
- ER aminopeptidase 1 (ERAP1) the name accepted by the Hugo Gene Nomenclature Committee[2]
- ER aminopeptidase associated with antigen processing (ERAAP)
- Adipocyte-derived leucine aminopeptidase (ALAP)
- Puromycin-insensitive leucine aminopeptidase (PILS-AP)
# Function
ERAP1 has two major functions in the immune system:
- First, ERAP1 cleaves several proteins called cytokine receptors on the surface of cells. Cleaving these receptors reduces their ability to transmit chemical signals into the cell, which affects the process of inflammation.
- Second, ERAP1 trims peptides within the endoplasmic reticulum so that they can be loaded onto major histocompatibility complex (MHC) class I. These peptides are attached to MHC class I in the endoplasmic reticulum and exported to the cell surface, where they are displayed to the immune system. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it responds by triggering the infected cell to self-destruct.[3]
ARTS-1 is a member of the M1 family of zinc metallopeptidases which acts as an aminopeptidase that degrades oligopeptides by cleavage starting at the amino terminus. One of the functions of aminopeptidases is to degrade potentially toxic peptides in the cytosol.[1]
ARTS-1 is a transmembrane protein that is localized to the endoplasmic reticulum. It has been implicated in the following functions:
- Shedding of various cytokine receptors and decoy receptors
- Trimming of antigenic peptides before binding to MHC class I, affecting antigen presentation to cytotoxic T lymphocytes
# Clinical significance
Aminopeptidases play a role in the metabolism of several peptides that may be involved in blood pressure and the pathogenesis of essential hypertension.[1] Mutations in the ARTS-1 have been linked to an increased risk of ankylosing spondylitis but only in HLA-B27 positive patients .[4]
The protein encoded by this gene is an aminopeptidase involved in trimming HLA class I-binding precursors so that they can be presented on MHC class I molecules. The encoded protein acts as a monomer or as a heterodimer with ERAP2. This protein may also be involved in blood pressure regulation by inactivation of angiotensin II. Three transcript variants encoding two different isoforms have been found for this gene.[1] | https://www.wikidoc.org/index.php/ARTS-1 | |
39a41f10b5872d35e24cb9c0fa6b78fcb0b416b0 | wikidoc | ARVD10 | ARVD10
Synonyms and keywords: Arrhythmogenic right ventricular dysplasia type 10; arrhythmogenic right ventricular cardiomyopathy 10; ARVC10
# Overview
Arrhythmogenic right ventricular dysplasia is a type of nonischemic cardiomyopathy that involves primarily the right ventricle. It is characterized by hypokinetic areas involving the free wall of the right ventricle, with fibrofatty replacement of the right ventricular myocardium, with associated arrhythmias originating in the right ventricle.
# Pathophysiology
The pathogenesis of ARVD involves apoptosis with fatty and fibro-fatty infiltration of the right ventricular free wall leading to heart failure and ventricular arrhythmias.
## Genetics
This variant ((610193) is associated with a mutation in the DSG2 gene (125671) on chromosome 18q12.1-q12.
# Epidemiology and Demographics
# Natural History, Complications, Prognosis
# Diagnosis
## Symptoms
## Electrocardiogram
## Echocardiogram
## MRI | ARVD10
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Arrhythmogenic right ventricular dysplasia type 10; arrhythmogenic right ventricular cardiomyopathy 10; ARVC10
# Overview
Arrhythmogenic right ventricular dysplasia is a type of nonischemic cardiomyopathy that involves primarily the right ventricle. It is characterized by hypokinetic areas involving the free wall of the right ventricle, with fibrofatty replacement of the right ventricular myocardium, with associated arrhythmias originating in the right ventricle.
# Pathophysiology
The pathogenesis of ARVD involves apoptosis with fatty and fibro-fatty infiltration of the right ventricular free wall leading to heart failure and ventricular arrhythmias.
## Genetics
This variant ((610193) is associated with a mutation in the DSG2 gene (125671) on chromosome 18q12.1-q12.[1]
# Epidemiology and Demographics
# Natural History, Complications, Prognosis
# Diagnosis
## Symptoms
## Electrocardiogram
## Echocardiogram
## MRI | https://www.wikidoc.org/index.php/ARVD10 | |
a9229909b9900d4e53cdcec9b97764322991bd2c | wikidoc | ARVD11 | ARVD11
Synonyms and keywords: Arrhythmogenic right ventricular dysplasia type 11; arrhythmogenic right ventricular cardiomyopathy 11; ARVC11
# Overview
Arrhythmogenic right ventricular dysplasia is a type of nonischemic cardiomyopathy that involves primarily the right ventricle. It is characterized by hypokinetic areas involving the free wall of the right ventricle, with fibrofatty replacement of the right ventricular myocardium, with associated arrhythmias originating in the right ventricle.
# Pathophysiology
The pathogenesis of ARVD involves apoptosis with fatty and fibro-fatty infiltration of the right ventricular free wall leading to heart failure and ventricular arrhythmias.
## Genetics
This variant (610476) is associated with a mutation in the DSC2 gene (125645) on chromosome 18q12.1.
# Epidemiology and Demographics
# Natural History, Complications, Prognosis
# Diagnosis
## Symptoms
## Electrocardiogram
## Echocardiogram
## MRI | ARVD11
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Arrhythmogenic right ventricular dysplasia type 11; arrhythmogenic right ventricular cardiomyopathy 11; ARVC11
# Overview
Arrhythmogenic right ventricular dysplasia is a type of nonischemic cardiomyopathy that involves primarily the right ventricle. It is characterized by hypokinetic areas involving the free wall of the right ventricle, with fibrofatty replacement of the right ventricular myocardium, with associated arrhythmias originating in the right ventricle.
# Pathophysiology
The pathogenesis of ARVD involves apoptosis with fatty and fibro-fatty infiltration of the right ventricular free wall leading to heart failure and ventricular arrhythmias.
## Genetics
This variant (610476) is associated with a mutation in the DSC2 gene (125645) on chromosome 18q12.1.[1]
# Epidemiology and Demographics
# Natural History, Complications, Prognosis
# Diagnosis
## Symptoms
## Electrocardiogram
## Echocardiogram
## MRI | https://www.wikidoc.org/index.php/ARVD11 | |
cd676bc2c808a2180f035936087660ce6eaf77c1 | wikidoc | ARVD12 | ARVD12
Synonyms and keywords: Arrhythmogenic right ventricular dysplasia type 12; arrhythmogenic right ventricular cardiomyopathy 12; ARVC12
# Overview
Arrhythmogenic right ventricular dysplasia is a type of nonischemic cardiomyopathy that involves primarily the right ventricle. It is characterized by hypokinetic areas involving the free wall of the right ventricle, with fibrofatty replacement of the right ventricular myocardium, with associated arrhythmias originating in the right ventricle.
# Pathophysiology
The pathogenesis of ARVD involves apoptosis with fatty and fibro-fatty infiltration of the right ventricular free wall leading to heart failure and ventricular arrhythmias.
## Genetics
This variant (611528) is associated with a mutation in the JUP gene (173325) on chromosome 17q21.
# Epidemiology and Demographics
# Natural History, Complications, Prognosis
# Diagnosis
## Symptoms
## Electrocardiogram
## Echocardiogram
## MRI | ARVD12
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Arrhythmogenic right ventricular dysplasia type 12; arrhythmogenic right ventricular cardiomyopathy 12; ARVC12
# Overview
Arrhythmogenic right ventricular dysplasia is a type of nonischemic cardiomyopathy that involves primarily the right ventricle. It is characterized by hypokinetic areas involving the free wall of the right ventricle, with fibrofatty replacement of the right ventricular myocardium, with associated arrhythmias originating in the right ventricle.
# Pathophysiology
The pathogenesis of ARVD involves apoptosis with fatty and fibro-fatty infiltration of the right ventricular free wall leading to heart failure and ventricular arrhythmias.
## Genetics
This variant (611528) is associated with a mutation in the JUP gene (173325) on chromosome 17q21.[1]
# Epidemiology and Demographics
# Natural History, Complications, Prognosis
# Diagnosis
## Symptoms
## Electrocardiogram
## Echocardiogram
## MRI | https://www.wikidoc.org/index.php/ARVD12 | |
e4858cb8c946c10349c6ada735ef197cb91757af | wikidoc | ASHRAE | ASHRAE
# Overview
The American Society of Heating, Refrigerating and Air Conditioning Engineers (ASHRAE; pronounced 'ash'-'ray') is an international technical society for all individuals and organizations interested in heating, ventilation, air-conditioning, and refrigeration (HVAC&R). The Society, organized into Regions, Chapters, and Student Branches, allows exchange of HVAC&R knowledge and experiences for the benefit of the field's practitioners and the public. ASHRAE provides many opportunities to participate in the development of new knowledge via, for example, research and its many Technical Committees. These committees meet typically twice per year at the ASHRAE Annual and Winter Meetings. A popular product show, the AHR Expo, is held in conjunction with each Winter Meeting.
# Publications
The ASHRAE Handbook is a four-volume resource for HVAC&R technology and is available in both print and electronic versions. The volumes are Fundamentals, HVAC Applications, HVAC Systems and Equipment, and Refrigeration. One of the four volumes is updated each year.
ASHRAE also publishes a well recognized series of standards and guidelines relating to HVAC systems and issues. These standards are often referenced in building codes. Examples of some ASHRAE Standards are:
- Standard 34 – Designation and Safety Classification of Refrigerants
- Standard 55 – Thermal Environmental Conditions for Human Occupancy
- Standard 62.1 – Ventilation for Acceptable Indoor Air Quality (versions: 2001 and earlier as "62", 2004 and beyond as "62.1")
- Standard 62.2 - Ventilation and Acceptable Indoor Air Quality in Low-Rise Residential Buildings
- Standard 90.1 - Energy Standard for Buildings Except Low-Rise Residential Buildings
- Standard 135 – BACnet - A Data Communication Protocol for Building Automation and Control Networks
These and many other ASHRAE Standards are periodically reviewed, revised, and published, so the year of publication of a particular standard is important for code compliance.
The ASHRAE Journal is a monthly magazine published by ASHRAE. It includes peer-reviewed articles on the practical application of HVAC&R technology, information on upcoming meetings and product shows, classified and display advertising, and editorials. Members of ASHRAE receive the magazine and the current year's volume of the ASHRAE Handbook as membership benefits. ASHRAE also publishes many books, ASHRAE Transactions, and the International Journal of HVAC&R Research.
# History
ASHRAE was founded in 1894 at a meeting of like-minded engineers in New York City. Until 1954 it was known as the American Society of Heating and Ventilating Engineers (ASHVE); in that year it changed its name to the American Society of Heating and Air-Conditioning Engineers (ASHAE). Its current name and organization came from the 1959 merger of ASHAE and the American Society of Refrigerating Engineers (ASRE). The result, ASHRAE, despite having 'American' in its name, is an influential international organization. Its 55,000 members worldwide are dedicated to advancing the arts and sciences of HVAC&R. ASHRAE's headquarters is in Atlanta, Georgia, USA.
# See Also
- The ASHRAE Handbook | ASHRAE
# Overview
The American Society of Heating, Refrigerating and Air Conditioning Engineers (ASHRAE; pronounced 'ash'-'ray') is an international technical society for all individuals and organizations interested in heating, ventilation, air-conditioning, and refrigeration (HVAC&R). The Society, organized into Regions, Chapters, and Student Branches, allows exchange of HVAC&R knowledge and experiences for the benefit of the field's practitioners and the public. ASHRAE provides many opportunities to participate in the development of new knowledge via, for example, research and its many Technical Committees. These committees meet typically twice per year at the ASHRAE Annual and Winter Meetings. A popular product show, the AHR Expo, is held in conjunction with each Winter Meeting.
# Publications
The ASHRAE Handbook is a four-volume resource for HVAC&R technology and is available in both print and electronic versions. The volumes are Fundamentals, HVAC Applications, HVAC Systems and Equipment, and Refrigeration. One of the four volumes is updated each year.
ASHRAE also publishes a well recognized series of standards and guidelines relating to HVAC systems and issues. These standards are often referenced in building codes. Examples of some ASHRAE Standards are:
- Standard 34 – Designation and Safety Classification of Refrigerants
- Standard 55 – Thermal Environmental Conditions for Human Occupancy
- Standard 62.1 – Ventilation for Acceptable Indoor Air Quality (versions: 2001 and earlier as "62", 2004 and beyond as "62.1")
- Standard 62.2 - Ventilation and Acceptable Indoor Air Quality in Low-Rise Residential Buildings
- Standard 90.1 - Energy Standard for Buildings Except Low-Rise Residential Buildings
- Standard 135 – BACnet - A Data Communication Protocol for Building Automation and Control Networks
These and many other ASHRAE Standards are periodically reviewed, revised, and published, so the year of publication of a particular standard is important for code compliance.
The ASHRAE Journal is a monthly magazine published by ASHRAE. It includes peer-reviewed articles on the practical application of HVAC&R technology, information on upcoming meetings and product shows, classified and display advertising, and editorials. Members of ASHRAE receive the magazine and the current year's volume of the ASHRAE Handbook as membership benefits. ASHRAE also publishes many books, ASHRAE Transactions, and the International Journal of HVAC&R Research.
# History
ASHRAE was founded in 1894 at a meeting of like-minded engineers in New York City. Until 1954 it was known as the American Society of Heating and Ventilating Engineers (ASHVE); in that year it changed its name to the American Society of Heating and Air-Conditioning Engineers (ASHAE). Its current name and organization came from the 1959 merger of ASHAE and the American Society of Refrigerating Engineers (ASRE). The result, ASHRAE, despite having 'American' in its name, is an influential international organization. Its 55,000 members worldwide are dedicated to advancing the arts and sciences of HVAC&R. ASHRAE's headquarters is in Atlanta, Georgia, USA.
# See Also
- The ASHRAE Handbook
# External links
- ASHRAE Web site
- ASHRAE publications
- The AHR Expo - Co-Sponsored by ASHRAE and ARI
- ASHRAE's License to Chill Rap Video on YouTube
- ASHRAE's Engineering for Sustainability
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Template:WS | https://www.wikidoc.org/index.php/ASHRAE | |
cc3b54fa5367e6462e384155eac30904f5dee56f | wikidoc | ASRGL1 | ASRGL1
L-asparaginase is an enzyme that in humans is encoded by the ASRGL1 gene.
# Function
The ASRGL1 protein consists of 308 amino acids and is activated by autocleavage at amino acid 168 to form an alpha- and a beta-chain, which can dimerize into a heterodimer. The ASRGL1 enzyme has both L-asparaginase and beta-aspartyl peptidase activity and may be involved in the production of L-aspartate, which can act as an excitatory neurotransmitter in some brain regions.
According to antibody-based profiling and transcriptomics analysis, ASRGL1 protein is present in all analysed human tissues, with highest expression in brain, in female tissues such as the uterine cervix and fallopian tube, and in male tissues as testis. Based on confocal microscopy ASRGL1 is mainly localized to the microtubules.
# Clinical significance
ASRGL1 is highly expressed in the normal endometrium and differentially expressed in endometrial cancer. Loss of ASRGL1 expression is an unfavorable prognostic feature for patients with endometrial cancer. | ASRGL1
L-asparaginase is an enzyme that in humans is encoded by the ASRGL1 gene.[1]
# Function
The ASRGL1 protein consists of 308 amino acids and is activated by autocleavage at amino acid 168 to form an alpha- and a beta-chain, which can dimerize into a heterodimer.[2] The ASRGL1 enzyme has both L-asparaginase and beta-aspartyl peptidase activity and may be involved in the production of L-aspartate, which can act as an excitatory neurotransmitter in some brain regions.
According to antibody-based profiling and transcriptomics analysis, ASRGL1 protein is present in all analysed human tissues, with highest expression in brain, in female tissues such as the uterine cervix and fallopian tube, and in male tissues as testis.[3] Based on confocal microscopy ASRGL1 is mainly localized to the microtubules.[4]
# Clinical significance
ASRGL1 is highly expressed in the normal endometrium and differentially expressed in endometrial cancer. Loss of ASRGL1 expression is an unfavorable prognostic feature for patients with endometrial cancer.[5][6] | https://www.wikidoc.org/index.php/ASRGL1 | |
17f0f2c24bdfe44c422e1fed642c7af3e33fcb1a | wikidoc | ATP1A2 | ATP1A2
ATPase, Na+/K+ transporting, alpha 2 (+) polypeptide, also known as ATP1A2, is a protein which in humans is encoded by the ATP1A2 gene.
# Function
The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+-ATPases. Na+/K+-ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+-ATPase is encoded by multiple genes. This gene encodes an alpha 2 subunit.
# Clinical significance
Mutations in the ATP1A2 gene has been implicated in the familial form of alternating hemiplegia of childhood. | ATP1A2
ATPase, Na+/K+ transporting, alpha 2 (+) polypeptide, also known as ATP1A2, is a protein which in humans is encoded by the ATP1A2 gene.[1]
# Function
The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+-ATPases. Na+/K+-ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+-ATPase is encoded by multiple genes. This gene encodes an alpha 2 subunit.[1]
# Clinical significance
Mutations in the ATP1A2 gene has been implicated in the familial form of alternating hemiplegia of childhood.[2][3][4] | https://www.wikidoc.org/index.php/ATP1A2 | |
11fd167a29ffca96b0c07c9d482a781bf38dc9ca | wikidoc | ATP1A3 | ATP1A3
Sodium/potassium-transporting ATPase subunit alpha-3 is an enzyme that in humans is encoded by the ATP1A3 gene.
# Function
The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+-ATPases. Na+/K+-ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+-ATPase is encoded by multiple genes. This gene encodes an alpha 3 subunit.
# Clinical significance
Mutations in ATP1A3 are often seen in rapid-onset dystonia–parkinsonism (RDP) (also known as DYT12), and genetic testing is recommended in patients where this diagnosis is suspected.
In mice, mutations in this gene are associated with epilepsy. By manipulating this gene in the offspring of such mice, epilepsy can be avoided.
This gene is the likely genetic cause of alternating hemiplegia of childhood. | ATP1A3
Sodium/potassium-transporting ATPase subunit alpha-3 is an enzyme that in humans is encoded by the ATP1A3 gene.[1][2]
# Function
The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+-ATPases. Na+/K+-ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+-ATPase is encoded by multiple genes. This gene encodes an alpha 3 subunit.[2]
# Clinical significance
Mutations in ATP1A3 are often seen in rapid-onset dystonia–parkinsonism (RDP) (also known as DYT12), and genetic testing is recommended in patients where this diagnosis is suspected.[citation needed]
In mice, mutations in this gene are associated with epilepsy. By manipulating this gene in the offspring of such mice, epilepsy can be avoided.[3]
This gene is the likely genetic cause of alternating hemiplegia of childhood.[4] | https://www.wikidoc.org/index.php/ATP1A3 | |
8e7c13b1dad25cbbff431f0719968e5bc833e133 | wikidoc | ATP2A1 | ATP2A1
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 is an enzyme that in humans is encoded by the ATP2A1 gene.
# Function
This gene encodes one of the SERCA Ca2+-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction.
# Clinical significance
Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in two transcript variants encoding different isoforms.
# Interactions
ATP2A1 has been shown to interact with:
- SLN, and
- PLN. | ATP2A1
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 is an enzyme that in humans is encoded by the ATP2A1 gene.[1]
# Function
This gene encodes one of the SERCA Ca2+-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction.[1]
# Clinical significance
Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in two transcript variants encoding different isoforms.[1]
# Interactions
ATP2A1 has been shown to interact with:
- SLN,[2][3] and
- PLN.[2][4][5] | https://www.wikidoc.org/index.php/ATP2A1 | |
3b5ac4a5b755c516e862e4a94a5bfc2668300f62 | wikidoc | ATP5C1 | ATP5C1
The human ATP5F1C gene encodes the gamma subunit of an enzyme called mitochondrial ATP synthase.
This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes adenosine triphosphate(ATP) synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation.
ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, F0, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the gamma subunit of the catalytic core.
Alternatively spliced transcript variants encoding different isoforms have been identified. This gene also has a pseudogene on chromosome 14. | ATP5C1
The human ATP5F1C gene encodes the gamma subunit of an enzyme called mitochondrial ATP synthase.[1][2][3]
This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes adenosine triphosphate(ATP) synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation.
ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, F0, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the gamma subunit of the catalytic core.
Alternatively spliced transcript variants encoding different isoforms have been identified. This gene also has a pseudogene on chromosome 14.[3] | https://www.wikidoc.org/index.php/ATP5C1 | |
2fa49053a14a201bc07307420c89a419f09623bb | wikidoc | ATP5F1 | ATP5F1
ATP synthase subunit b, mitochondrial is an enzyme that in humans is encoded by the ATP5PB gene.
This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the b subunit of the proton channel.
The b subunits are part of the peripheral stalk that links the F1 and FO complexes together, and which acts as a stator to prevent certain subunits from rotating with the central rotary element. The peripheral stalk differs in subunit composition between mitochondrial, chloroplast and bacterial F-ATPases. In bacterial and chloroplast F-ATPases, the peripheral stalk is composed of one copy of the delta subunit (homologous to OSCP in mitochondria), and two copies of subunit b in bacteria, or one copy each of subunits b and b' in chloroplasts and photosynthetic bacteria. | ATP5F1
ATP synthase subunit b, mitochondrial is an enzyme that in humans is encoded by the ATP5PB gene.[1][2]
This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the b subunit of the proton channel.[2]
The b subunits are part of the peripheral stalk that links the F1 and FO complexes together, and which acts as a stator to prevent certain subunits from rotating with the central rotary element. The peripheral stalk differs in subunit composition between mitochondrial, chloroplast and bacterial F-ATPases. In bacterial and chloroplast F-ATPases, the peripheral stalk is composed of one copy of the delta subunit (homologous to OSCP in mitochondria), and two copies of subunit b in bacteria, or one copy each of subunits b and b' in chloroplasts and photosynthetic bacteria.[3] | https://www.wikidoc.org/index.php/ATP5F1 | |
0c82591f725f86de5e769bf0ba2f24455e57fa74 | wikidoc | ATP8B3 | ATP8B3
The human gene ATP8B3 encodes the protein ATPase, aminophospholipid transporter, class I, type 8B, member 3.
The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. This gene encodes the member 3 of the phospholipid-transporting ATPase 8B.
Alternatively spliced transcript variants encoding different isoforms have been found for this gene. | ATP8B3
The human gene ATP8B3 encodes the protein ATPase, aminophospholipid transporter, class I, type 8B, member 3.[1]
The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. This gene encodes the member 3 of the phospholipid-transporting ATPase 8B.
Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[1] | https://www.wikidoc.org/index.php/ATP8B3 | |
8f7a998596e09149c2a1904cde868e442912ec73 | wikidoc | ATPAF2 | ATPAF2
ATP synthase mitochondrial F1 complex assembly factor 2 is an enzyme that in humans is encoded by the ATPAF2 gene.
This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 alpha subunit and is thought to prevent the subunit from forming nonproductive homooligomers during enzyme assembly. This gene is located within the Smith-Magenis syndrome region on chromosome 17. An alternatively spliced transcript variant has been described, but its biological validity has not been determined. A mutation in this gene has caused nuclear type 1 Complex V deficiency, characterized by lactic acidosis, encephalopathy, and developmental delays.
# Structure
The ATPAF2 gene is located on the p arm of chromosome 17 in position 11.2 and spans 24,110 base pairs. The gene produces a 32.8 kDa protein composed of 289 amino acids. This gene has at least 8 exons and is located within the Smith-Magenis syndrome region on chromosome 17.
# Function
The ATPAF2 gene encodes an essential housekeeping protein, an assembly factor for the F1 component of mitochondrial ATP synthase. This protein binds specifically to the F1 alpha subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly.
# Clinical Significance
In the only report of a mutation in the ATPAF2 gene, the resulting phenotype was nuclear type 1 Complex V deficiency inherited in an autosomal recessive manner. A homozygous 280T-A transversion caused a W94R amino acid substitution adjacent to a highly conserved glutamine. Symptoms included elevated blood, CSF, and urine lactate levels, developmental delays with failure to thrive and seizures, and a degenerative encephalopathy with cortical and subcortical atrophy.
# Interactions
The encoded protein interacts with ATP5F1A and FMC1, along with many other proteins.
# Model organisms
Model organisms have been used in the study of ATPAF2 function. A conditional knockout mouse line, called Atpaf2tm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty six tests were carried out on mutant mice and three significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; males had abnormal vertebrae morphology. | ATPAF2
ATP synthase mitochondrial F1 complex assembly factor 2 is an enzyme that in humans is encoded by the ATPAF2 gene.[1][2][3]
This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 alpha subunit and is thought to prevent the subunit from forming nonproductive homooligomers during enzyme assembly. This gene is located within the Smith-Magenis syndrome region on chromosome 17. An alternatively spliced transcript variant has been described, but its biological validity has not been determined.[3] A mutation in this gene has caused nuclear type 1 Complex V deficiency, characterized by lactic acidosis, encephalopathy, and developmental delays.[4][5]
# Structure
The ATPAF2 gene is located on the p arm of chromosome 17 in position 11.2 and spans 24,110 base pairs.[3] The gene produces a 32.8 kDa protein composed of 289 amino acids.[6][7] This gene has at least 8 exons and is located within the Smith-Magenis syndrome region on chromosome 17.[3]
# Function
The ATPAF2 gene encodes an essential housekeeping protein, an assembly factor for the F1 component of mitochondrial ATP synthase. This protein binds specifically to the F1 alpha subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly.[1][3]
# Clinical Significance
In the only report of a mutation in the ATPAF2 gene, the resulting phenotype was nuclear type 1 Complex V deficiency inherited in an autosomal recessive manner. A homozygous 280T-A transversion caused a W94R amino acid substitution adjacent to a highly conserved glutamine. Symptoms included elevated blood, CSF, and urine lactate levels, developmental delays with failure to thrive and seizures, and a degenerative encephalopathy with cortical and subcortical atrophy.[4][5]
# Interactions
The encoded protein interacts with ATP5F1A and FMC1, along with many other proteins.[1][8][9]
# Model organisms
Model organisms have been used in the study of ATPAF2 function. A conditional knockout mouse line, called Atpaf2tm1a(KOMP)Wtsi[15][16] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[17][18][19]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[13][20] Twenty six tests were carried out on mutant mice and three significant abnormalities were observed.[13] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; males had abnormal vertebrae morphology.[13] | https://www.wikidoc.org/index.php/ATPAF2 | |
ed69fb5f932c6873f028f900320bcf8b2deefcfe | wikidoc | ATPIF1 | ATPIF1
ATPase inhibitor, mitochondrial is an enzyme that in humans is encoded by the ATPIF1 gene.
This gene encodes a mitochondrial ATPase inhibitor. Alternative splicing occurs at this locus and three transcript variants encoding distinct isoforms have been identified.
It prevents ATPase from switching to ATP hydrolysis during collapse of the electrochemical gradient, for example during oxygen deprivation ATP synthase inhibitor forms a one-to-one complex with the F1 ATPase, possibly by binding at the alpha-beta interface. It is thought to inhibit ATP synthesis by preventing the release of ATP. The inhibitor has two oligomeric states, dimer (the active state) and tetramer. At low pH, the inhibitor forms a dimer via antiparallel coiled coil interactions between the C-terminal regions of two monomers. At high pH, the inhibitor forms tetramers and higher oligomers by coiled coil interactions involving the N terminus and inhibitory region, thus preventing the inhibitory activity.
# Model organisms
Model organisms have been used in the study of ATPIF1 function. A conditional knockout mouse line, called Atpif1tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty three tests were carried out on mutant mice and three significant abnormalities were observed. Homozygous mutant animals displayed hyperactivity and brain dysmorphology, while males also had decreased circulating alkaline phosphatase levels. | ATPIF1
ATPase inhibitor, mitochondrial is an enzyme that in humans is encoded by the ATPIF1 gene.[1][2]
This gene encodes a mitochondrial ATPase inhibitor. Alternative splicing occurs at this locus and three transcript variants encoding distinct isoforms have been identified.[2]
It prevents ATPase from switching to ATP hydrolysis during collapse of the electrochemical gradient, for example during oxygen deprivation [3] ATP synthase inhibitor forms a one-to-one complex with the F1 ATPase, possibly by binding at the alpha-beta interface. It is thought to inhibit ATP synthesis by preventing the release of ATP.[4] The inhibitor has two oligomeric states, dimer (the active state) and tetramer. At low pH, the inhibitor forms a dimer via antiparallel coiled coil interactions between the C-terminal regions of two monomers. At high pH, the inhibitor forms tetramers and higher oligomers by coiled coil interactions involving the N terminus and inhibitory region, thus preventing the inhibitory activity.[3]
# Model organisms
Model organisms have been used in the study of ATPIF1 function. A conditional knockout mouse line, called Atpif1tm1a(EUCOMM)Wtsi[11][12] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[13][14][15]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty three tests were carried out on mutant mice and three significant abnormalities were observed.[9] Homozygous mutant animals displayed hyperactivity and brain dysmorphology, while males also had decreased circulating alkaline phosphatase levels.[9] | https://www.wikidoc.org/index.php/ATPIF1 | |
3b68169e0f65d76c28e2e2dec13d004435cafcdf | wikidoc | ATPase | ATPase
# Overview
ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate (ATP) into adenosine diphosphate (ADP) and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme (in most cases) harnesses to drive other chemical reactions that would not otherwise occur. This process is widely used in all known forms of life.
Some such enzymes are integral membrane proteins (anchored within biological membranes), and move solutes across the membrane. (These are called transmembrane ATPases).
# Functions
Transmembrane ATPases import many of the metabolites necessary for cell metabolism and export toxins, wastes, and solutes that can hinder cellular processes. An important example is the sodium-potassium exchanger (or Na+/K+ATPase), which establishes the ionic concentration balance that maintains the cell potential. Another example is the hydrogen potassium ATPase (H+/K+ATPase or gastric proton pump) that acidifies the contents of the stomach.
Besides exchangers, other categories of transmembrane ATPase include co-transporters and pumps (however, some exchangers are also pumps). Some of these, like the Na+/K+ATPase, cause a net flow of charge, but others do not. These are called "electrogenic" and "nonelectrogenic" transporters, respectively.
# Mechanism
The coupling between ATP hydrolysis and transport is more or less a strict chemical reaction, in which a fixed number of solute molecules are transported for each ATP molecule that is hydrolyzed; for example, 3 Na+ ions out of the cell and 2 K+ ions inward per ATP hydrolyzed, for the Na+/K+ exchanger.
Transmembrane ATPases harness the chemical potential energy of ATP, because they perform mechanical work: they transport solutes in a direction opposite to their thermodynamically preferred direction of movement—that is, from the side of the membrane where they are in low concentration to the side where they are in high concentration. This process is considered active transport.
For example, the blocking of the vesicular H+-ATPAses would increase the pH inside vesicles and decrease the pH of the cytoplasm.
# ATP synthase
The ATP synthase of mitochondria and chloroplasts is an anabolic enzyme that harnesses the energy of a transmembrane proton gradient as an energy source for adding an inorganic phosphate group to a molecule of adenosine diphosphate (ADP) to form a molecule of adenosine triphosphate (ATP).
This enzyme works when a proton moves down the concentration gradient, giving the enzyme a spinning motion. This unique spinning motion bonds ADP and P together to create ATP.
ATP synthase can also function in reverse, that is, use energy released by ATP hydrolysis to pump protons against their thermodynamic gradient.
# Classification
There are different types of ATPases, which can differ in function (ATP synthesis and/or hydrolysis), structure (F-, V- and A-ATPases contain rotary motors) and in the type of ions they transport.
- F-ATPases (F1F0-ATPases) in mitochondria, chloroplasts and bacterial plasma membranes are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).
- V-ATPases (V1V0-ATPases) are primarily found in eukaryotic vacuoles, catalysing ATP hydrolysis to transport solutes and lower pH in organelles.
- A-ATPases (A1A0-ATPases) are found in Archaea and function like F-ATPases.
- P-ATPases (E1E2-ATPases) are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.
- E-ATPases are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.
## P-ATPase
P-ATPases (sometime known as E1-E2 ATPases) are found in bacteria and in a number of eukaryotic plasma membranes and organelles. P-ATPases function to transport a variety of different compounds, including ions and phospholipids, across a membrane using ATP hydrolysis for energy. There are many different classes of P-ATPases, each of which transports a specific type of ion: H+, Na+, K+, Mg2+, Ca2+, Ag+ and Ag2+, Zn2+, Co2+, Pb2+, Ni2+, Cd2+, Cu+ and Cu2+. P-ATPases can be composed of one or two polypeptides, and can usually assume two main conformations called E1 and E2.
# Human genes
- Na+/K+ transporting: ATP1A1, ATP1A2, ATP1A3, ATP1A4, ATP1B1, ATP1B2, ATP1B3, ATP1B4
- Ca++ transporting: ATP2A1, ATP2A2, ATP2A3, ATP2B1, ATP2B2, ATP2B3, ATP2B4, ATP2C1
- Mg++ transporting: ATP3
- H+/K+ exchanging: ATP4A, ATP4B
- H+ transporting, mitochondrial: ATP5A1, ATP5B, ATP5C1, ATP5C2, ATP5D, ATP5E, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5H, ATP5I, ATP5J, ATP5J2, ATP5L, ATP5L2, ATP5O, ATP5S
- H+ transporting, lysosomal: ATP6AP1, ATP6AP2, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E
- Cu++ transporting: ATP7A (see also ATP7A), ATP7B (see also ATP7B)
- Class I, type 8: ATP8A1, ATP8B1, ATP8B2, ATP8B3, ATP8B4
- Class II, type 9: ATP9A, ATP9B
- Class V, type 10: ATP10A, ATP10B, ATP10D
- Class VI, type 11: ATP11A, ATP11B, ATP11C
- H+/K+ transporting, nongastric: ATP12A
- type 13: ATP13A1, ATP13A2, ATP13A3, ATP13A4, ATP13A5 | ATPase
# Overview
ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate (ATP) into adenosine diphosphate (ADP) and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme (in most cases) harnesses to drive other chemical reactions that would not otherwise occur. This process is widely used in all known forms of life.
Some such enzymes are integral membrane proteins (anchored within biological membranes), and move solutes across the membrane. (These are called transmembrane ATPases).
# Functions
Transmembrane ATPases import many of the metabolites necessary for cell metabolism and export toxins, wastes, and solutes that can hinder cellular processes. An important example is the sodium-potassium exchanger (or Na+/K+ATPase), which establishes the ionic concentration balance that maintains the cell potential. Another example is the hydrogen potassium ATPase (H+/K+ATPase or gastric proton pump) that acidifies the contents of the stomach.
Besides exchangers, other categories of transmembrane ATPase include co-transporters and pumps (however, some exchangers are also pumps). Some of these, like the Na+/K+ATPase, cause a net flow of charge, but others do not. These are called "electrogenic" and "nonelectrogenic" transporters, respectively.
# Mechanism
The coupling between ATP hydrolysis and transport is more or less a strict chemical reaction, in which a fixed number of solute molecules are transported for each ATP molecule that is hydrolyzed; for example, 3 Na+ ions out of the cell and 2 K+ ions inward per ATP hydrolyzed, for the Na+/K+ exchanger.
Transmembrane ATPases harness the chemical potential energy of ATP, because they perform mechanical work: they transport solutes in a direction opposite to their thermodynamically preferred direction of movement—that is, from the side of the membrane where they are in low concentration to the side where they are in high concentration. This process is considered active transport.
For example, the blocking of the vesicular H+-ATPAses would increase the pH inside vesicles and decrease the pH of the cytoplasm.
# ATP synthase
The ATP synthase of mitochondria and chloroplasts is an anabolic enzyme that harnesses the energy of a transmembrane proton gradient as an energy source for adding an inorganic phosphate group to a molecule of adenosine diphosphate (ADP) to form a molecule of adenosine triphosphate (ATP).
This enzyme works when a proton moves down the concentration gradient, giving the enzyme a spinning motion. This unique spinning motion bonds ADP and P together to create ATP.
ATP synthase can also function in reverse, that is, use energy released by ATP hydrolysis to pump protons against their thermodynamic gradient.
# Classification
There are different types of ATPases, which can differ in function (ATP synthesis and/or hydrolysis), structure (F-, V- and A-ATPases contain rotary motors) and in the type of ions they transport.
- F-ATPases (F1F0-ATPases) in mitochondria, chloroplasts and bacterial plasma membranes are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).
- V-ATPases (V1V0-ATPases) are primarily found in eukaryotic vacuoles, catalysing ATP hydrolysis to transport solutes and lower pH in organelles.
- A-ATPases (A1A0-ATPases) are found in Archaea and function like F-ATPases.
- P-ATPases (E1E2-ATPases) are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.
- E-ATPases are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.
## P-ATPase
P-ATPases (sometime known as E1-E2 ATPases) are found in bacteria and in a number of eukaryotic plasma membranes and organelles. P-ATPases function to transport a variety of different compounds, including ions and phospholipids, across a membrane using ATP hydrolysis for energy. There are many different classes of P-ATPases, each of which transports a specific type of ion: H+, Na+, K+, Mg2+, Ca2+, Ag+ and Ag2+, Zn2+, Co2+, Pb2+, Ni2+, Cd2+, Cu+ and Cu2+. P-ATPases can be composed of one or two polypeptides, and can usually assume two main conformations called E1 and E2.
# Human genes
- Na+/K+ transporting: ATP1A1, ATP1A2, ATP1A3, ATP1A4, ATP1B1, ATP1B2, ATP1B3, ATP1B4
- Ca++ transporting: ATP2A1, ATP2A2, ATP2A3, ATP2B1, ATP2B2, ATP2B3, ATP2B4, ATP2C1
- Mg++ transporting: ATP3
- H+/K+ exchanging: ATP4A, ATP4B
- H+ transporting, mitochondrial: ATP5A1, ATP5B, ATP5C1, ATP5C2, ATP5D, ATP5E, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5H, ATP5I, ATP5J, ATP5J2, ATP5L, ATP5L2, ATP5O, ATP5S
- H+ transporting, lysosomal: ATP6AP1, ATP6AP2, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E
- Cu++ transporting: ATP7A (see also ATP7A), ATP7B (see also ATP7B)
- Class I, type 8: ATP8A1, ATP8B1, ATP8B2, ATP8B3, ATP8B4
- Class II, type 9: ATP9A, ATP9B
- Class V, type 10: ATP10A, ATP10B, ATP10D
- Class VI, type 11: ATP11A, ATP11B, ATP11C
- H+/K+ transporting, nongastric: ATP12A
- type 13: ATP13A1, ATP13A2, ATP13A3, ATP13A4, ATP13A5 | https://www.wikidoc.org/index.php/ATPase | |
0dbcd99d7c86142981d6eee96fdfbd66cd831c2a | wikidoc | ATXN2L | ATXN2L
Ataxin-2-like protein is a protein that in humans is encoded by the ATXN2L gene.
This gene encodes an ataxin type 2 related protein of unknown function. This protein is a member of the spinocerebellar ataxia (SCAs) family, which is associated with a complex group of neurodegenerative disorders. Several alternatively spliced transcripts encoding different isoforms have been found for this gene.
# Interactions
ATXN2L has been shown to interact with Myeloproliferative leukemia virus oncogene. | ATXN2L
Ataxin-2-like protein is a protein that in humans is encoded by the ATXN2L gene.[1][2][3]
This gene encodes an ataxin type 2 related protein of unknown function. This protein is a member of the spinocerebellar ataxia (SCAs) family, which is associated with a complex group of neurodegenerative disorders. Several alternatively spliced transcripts encoding different isoforms have been found for this gene.[3]
# Interactions
ATXN2L has been shown to interact with Myeloproliferative leukemia virus oncogene.[1] | https://www.wikidoc.org/index.php/ATXN2L | |
b08b640dcc87f270752ea5ee96fbf076e39785df | wikidoc | Abasia | Abasia
# Overview
Abasia (from Greek: a-, without and basis, step) is the inability to walk due to impaired muscle coordination. The American Heritage Medical Dictionary defines abasia as "Inability to walk due to impaired muscular coordination.a"
The term covers a spectrum of medical disorders such as:
- choreic abasia: caused by chorea of the legs
- paralytic abasia: caused by paralysis of the leg muscles
- spastic abasia: caused by spastic stiffening of the leg muscles
- trembling abasia: caused by trembling of the legs
Abasia is frequently accompanied by astasis, an inability to stand, see Astasia-abasia. | Abasia
# Overview
Abasia (from Greek: a-, without and basis, step) is the inability to walk due to impaired muscle coordination. The American Heritage Medical Dictionary defines abasia as "Inability to walk due to impaired muscular coordination.a" [1]
The term covers a spectrum of medical disorders such as:
- choreic abasia: caused by chorea of the legs
- paralytic abasia: caused by paralysis of the leg muscles
- spastic abasia: caused by spastic stiffening of the leg muscles
- trembling abasia: caused by trembling of the legs
Abasia is frequently accompanied by astasis, an inability to stand, see Astasia-abasia. | https://www.wikidoc.org/index.php/Abasia | |
2535a4ee04ad1064365b91bf33e02572c4e6d070 | wikidoc | Sputum | Sputum
# Overview
Sputum is expectorated matter especially from the air passages in diseases of the lungs, bronchi, or upper respiratory tract. It is matter that is coughed up from the respiratory tract, such as mucus or phlegm, mixed with saliva and then expectorated from the mouth.
# Causes
## Life Threatening Causes
- Amyloidosis
- Hiv
- Infective endocarditis
- Kidney cancer
- Liver cancer
- Malignant rhabdoid tumors
- Melanoma
- Parkinson's disease
- Penis cancer
- Prostate cancer
- Renal cancer
- Renal failure
- Sarcoma botryoides
- Tuberculosis
- Ureter cancer
- Urethral cancer
- Urinary system cancer
- Wilms tumor
## Common Causes
- Acute pulmonary edema
- Alveolar hydatid disease
- Amoebic abscess
- Amyloidosis
- Aspergillosis
- Asthma
- Atypical pneumonia
- Bacterial pneumonia
- Bacteriodes
- Bronchiectasis
- Bronchitis
- Bronchogenic cyst
- Chronic obstructive pulmonary disease
- Cystic fibrosis
- Diffuse mucopurulent bronchitis
- Diffuse panbronchiolitis
- Echinococcus granulosus
- Empyema with pleuro-bronchial fistula
- Foreign body in respiratory tract
- Granulomatosis with polyangiitis
- Hughes-stovin syndrome
- Hydatid cyst
- Idiopathic pulmonary haemosiderosis
- Laryngeal carcinoma
- Legionaires disease
- Lung abscess
- Lymphangiomyomatosis
- Lymphomatoid granulomatosis
- Maple bark stripper lung disease
- Measles
- Moraxella catarrhalis
- Mycobacterium tuberculosis
- Plague
- Pleural empyema
- Pneumococcal infection
- Pneumocystis
- Pneumonia
- Pseudomonas aeruginosa infection
- Pulmonary alveolar proteinosis
- Pulmonary arterio-venous malformation
- Pulmonary congestion
- Pulmonary edema
- Pulmonary embolism
- Pulmonary hypertension
- Pulmonary infarction
- Pulmonary infections
- Right middle lobe syndrome
- Staphylococcal infection
- Staphylococcus
- Streptococuus pneumonia
- Tropical pulmonary eosinophilia
- Yersinia pestis
## Causes by Organ System
## Causes in Alphabetical Order
- Actinomycosis
- Acute pulmonary edema
- Allergic bronchopulmonary aspergillosis
- Alveolar hydatid disease
- Amoebic abscess
- Amyloidosis
- Aspergillosis
- Asthma
- Atypical pneumonia
- Bacterial pneumonia
- Bacteriodes
- Bronchial adenoma
- Bronchiectasis
- Bronchitis
- Bronchogenic carcinoma
- Bronchogenic cyst
- Carbamoylphosphate synthetase deficiency
- Cardiac failure
- Chronic obstructive pulmonary disease
- Common variable immune deficiency
- Cyst
- Cystic fibrosis
- Defibrotide
- Dengue
- Dicoumarol
- Diffuse mucopurulent bronchitis
- Diffuse panbronchiolitis
- Echinococcus granulosus
- E-coli
- Empyema with pleuro-bronchial fistula
- Foreign body in respiratory tract
- Goodpasture syndrome
- Granulomatosis with polyangiitis
- Haemophilus influenzae
- Hereditary haemorrhagic telangiectasia
- Histiocytosis x
- Hiv
- Hughes-stovin syndrome
- Hydatid cyst
- Idiopathic pulmonary haemosiderosis
- Igg deficiency
- Immunocompromise
- Immunodeficiency
- Klebsiella
- Laryngeal carcinoma
- Legionaires disease
- Lung abscess
- Lymphangiomyomatosis
- Lymphomatoid granulomatosis
- Maple bark stripper lung disease
- Measles
- Mediastinal abscess
- Melioidosis
- Mercaptopropionylglycine
- Microscopic polyangiitis
- Mitral valve stenosis
- Moraxella catarrhalis
- Mycobacterium tuberculosis
- Oropharyngeal cancer
- Paracoccidioidomycosis
- Paragonimiasis
- Peptostreptococcus
- Phenprocoumon
- Plague
- Pleural empyema
- Pneumococcal infection
- Pneumocystis
- Pneumonia
- Pseudomonas aeruginosa infection
- Pulmonary alveolar proteinosis
- Pulmonary arterio-venous malformation
- Pulmonary congestion
- Pulmonary edema
- Pulmonary embolism
- Pulmonary hypertension
- Pulmonary infarction
- Pulmonary infections
- Right middle lobe syndrome
- Staphylococcal infection
- Staphylococcus
- Streptococuus pneumonia
- Systemic lupus erythematosus
- Tonsillitis
- Tropical pulmonary eosinophilia
- Tuberculosis
- Warfarin
- Wegener's granulomatosis
- Yersinia pestis
# Diagnosis
A sputum sample is the name given to the mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections.
The best sputum samples contain very little saliva, as this contaminates the sample with oral bacteria.
When a sputum specimen is plated out, it is best to get the portion of the sample that most looks like pus onto the swab. If there is any blood in the sputum, this should also be on the swab.
Microbiological sputum samples are usually used to look for infections by Moraxella catarrhalis, Mycobacterium tuberculosis, Streptococcus pneumoniae and Haemophilus influenzae. Other pathogens can also be found.
Purulent Sputum is that containing, or consisting of, pus. | Sputum
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Luke Rusowicz-Orazem, B.S.
# Overview
Sputum is expectorated matter especially from the air passages in diseases of the lungs, bronchi, or upper respiratory tract. It is matter that is coughed up from the respiratory tract, such as mucus or phlegm, mixed with saliva and then expectorated from the mouth.
# Causes
## Life Threatening Causes
- Amyloidosis
- Hiv
- Infective endocarditis
- Kidney cancer
- Liver cancer
- Malignant rhabdoid tumors
- Melanoma
- Parkinson's disease
- Penis cancer
- Prostate cancer
- Renal cancer
- Renal failure
- Sarcoma botryoides
- Tuberculosis
- Ureter cancer
- Urethral cancer
- Urinary system cancer
- Wilms tumor
## Common Causes
- Acute pulmonary edema
- Alveolar hydatid disease
- Amoebic abscess
- Amyloidosis
- Aspergillosis
- Asthma
- Atypical pneumonia
- Bacterial pneumonia
- Bacteriodes
- Bronchiectasis
- Bronchitis
- Bronchogenic cyst
- Chronic obstructive pulmonary disease
- Cystic fibrosis
- Diffuse mucopurulent bronchitis
- Diffuse panbronchiolitis
- Echinococcus granulosus
- Empyema with pleuro-bronchial fistula
- Foreign body in respiratory tract
- Granulomatosis with polyangiitis
- Hughes-stovin syndrome
- Hydatid cyst
- Idiopathic pulmonary haemosiderosis
- Laryngeal carcinoma
- Legionaires disease
- Lung abscess
- Lymphangiomyomatosis
- Lymphomatoid granulomatosis
- Maple bark stripper lung disease
- Measles
- Moraxella catarrhalis
- Mycobacterium tuberculosis
- Plague
- Pleural empyema
- Pneumococcal infection
- Pneumocystis
- Pneumonia
- Pseudomonas aeruginosa infection
- Pulmonary alveolar proteinosis
- Pulmonary arterio-venous malformation
- Pulmonary congestion
- Pulmonary edema
- Pulmonary embolism
- Pulmonary hypertension
- Pulmonary infarction
- Pulmonary infections
- Right middle lobe syndrome
- Staphylococcal infection
- Staphylococcus
- Streptococuus pneumonia
- Tropical pulmonary eosinophilia
- Yersinia pestis
## Causes by Organ System
## Causes in Alphabetical Order
- Actinomycosis
- Acute pulmonary edema
- Allergic bronchopulmonary aspergillosis
- Alveolar hydatid disease
- Amoebic abscess
- Amyloidosis
- Aspergillosis
- Asthma
- Atypical pneumonia
- Bacterial pneumonia
- Bacteriodes
- Bronchial adenoma
- Bronchiectasis
- Bronchitis
- Bronchogenic carcinoma
- Bronchogenic cyst
- Carbamoylphosphate synthetase deficiency
- Cardiac failure
- Chronic obstructive pulmonary disease
- Common variable immune deficiency
- Cyst
- Cystic fibrosis
- Defibrotide
- Dengue
- Dicoumarol
- Diffuse mucopurulent bronchitis
- Diffuse panbronchiolitis
- Echinococcus granulosus
- E-coli
- Empyema with pleuro-bronchial fistula
- Foreign body in respiratory tract
- Goodpasture syndrome
- Granulomatosis with polyangiitis
- Haemophilus influenzae
- Hereditary haemorrhagic telangiectasia
- Histiocytosis x
- Hiv
- Hughes-stovin syndrome
- Hydatid cyst
- Idiopathic pulmonary haemosiderosis
- Igg deficiency
- Immunocompromise
- Immunodeficiency
- Klebsiella
- Laryngeal carcinoma
- Legionaires disease
- Lung abscess
- Lymphangiomyomatosis
- Lymphomatoid granulomatosis
- Maple bark stripper lung disease
- Measles
- Mediastinal abscess
- Melioidosis
- Mercaptopropionylglycine
- Microscopic polyangiitis
- Mitral valve stenosis
- Moraxella catarrhalis
- Mycobacterium tuberculosis
- Oropharyngeal cancer
- Paracoccidioidomycosis
- Paragonimiasis
- Peptostreptococcus
- Phenprocoumon
- Plague
- Pleural empyema
- Pneumococcal infection
- Pneumocystis
- Pneumonia
- Pseudomonas aeruginosa infection
- Pulmonary alveolar proteinosis
- Pulmonary arterio-venous malformation
- Pulmonary congestion
- Pulmonary edema
- Pulmonary embolism
- Pulmonary hypertension
- Pulmonary infarction
- Pulmonary infections
- Right middle lobe syndrome
- Staphylococcal infection
- Staphylococcus
- Streptococuus pneumonia
- Systemic lupus erythematosus
- Tonsillitis
- Tropical pulmonary eosinophilia
- Tuberculosis
- Warfarin
- Wegener's granulomatosis
- Yersinia pestis
# Diagnosis
A sputum sample is the name given to the mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections.
The best sputum samples contain very little saliva, as this contaminates the sample with oral bacteria.
When a sputum specimen is plated out, it is best to get the portion of the sample that most looks like pus onto the swab. If there is any blood in the sputum, this should also be on the swab.
Microbiological sputum samples are usually used to look for infections by Moraxella catarrhalis, Mycobacterium tuberculosis, Streptococcus pneumoniae and Haemophilus influenzae. Other pathogens can also be found.
Purulent Sputum is that containing, or consisting of, pus. | https://www.wikidoc.org/index.php/Abnormal_sputum | |
ef4052e24493b48e54742b879dc4acfd3eb1794d | wikidoc | Acetyl | Acetyl
# Overview
In organic chemistry, acetyl (ethanoyl), is a functional group, the acyl of acetic acid, with chemical formula -COCH3. It is sometimes abbreviated as Ac (not to be confused with the element actinium). The acetyl radical contains a methyl group single-bonded to a carbonyl. The carbon of the carbonyl has a lone electron available, with which it forms a chemical bond to the remainder R of the molecule.
The acetyl radical is a component of many organic compounds, including the neurotransmitter acetylcholine, and acetyl-CoA, and the analgesics acetaminophen and acetylsalicylic acid (better known as aspirin).
# Acetylation
The introduction of an acetyl group into a molecule is called acetylation (or ethanoylation). In biological organisms, acetyl groups are commonly transferred bound to Coenzyme A (CoA), in the form of acetyl-CoA. Acetyl-CoA is an important intermediate both in the biological synthesis and in the breakdown of many organic molecules.
Acetyl groups are also frequently added to histones and other proteins modifying their properties. For example, on the DNA level, Histone acetylation by acetyltransferases (HATs) causes an expansion of chromatin architecture allowing for genetic transcription to take place. Conversely, removal of the acetyl group by histone deacetylases (HDACs) condenses DNA structure, thereby preventing transcription.
# Pharmacology
When acetyl groups are bound to certain other organic molecules, they impart an increased ability to cross the blood-brain barrier. This makes the drug reach the brain more quickly, making the drug's effects more intense and increasing the effectiveness of a given dose. Acetyl groups are used to make the natural antiinflammitant salicylic acid into the more effective acetylsalicylic acid, or aspirin. Similarly, they make the natural painkiller morphine into diacetylmorphine, or heroin. | Acetyl
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
In organic chemistry, acetyl (ethanoyl), is a functional group, the acyl of acetic acid, with chemical formula -COCH3. It is sometimes abbreviated as Ac (not to be confused with the element actinium). The acetyl radical contains a methyl group single-bonded to a carbonyl. The carbon of the carbonyl has a lone electron available, with which it forms a chemical bond to the remainder R of the molecule.
The acetyl radical is a component of many organic compounds, including the neurotransmitter acetylcholine, and acetyl-CoA, and the analgesics acetaminophen and acetylsalicylic acid (better known as aspirin).
# Acetylation
The introduction of an acetyl group into a molecule is called acetylation (or ethanoylation). In biological organisms, acetyl groups are commonly transferred bound to Coenzyme A (CoA), in the form of acetyl-CoA. Acetyl-CoA is an important intermediate both in the biological synthesis and in the breakdown of many organic molecules.
Acetyl groups are also frequently added to histones and other proteins modifying their properties. For example, on the DNA level, Histone acetylation by acetyltransferases (HATs) causes an expansion of chromatin architecture allowing for genetic transcription to take place. Conversely, removal of the acetyl group by histone deacetylases (HDACs) condenses DNA structure, thereby preventing transcription.[1]
# Pharmacology
When acetyl groups are bound to certain other organic molecules, they impart an increased ability to cross the blood-brain barrier. This makes the drug reach the brain more quickly, making the drug's effects more intense and increasing the effectiveness of a given dose. Acetyl groups are used to make the natural antiinflammitant salicylic acid into the more effective acetylsalicylic acid, or aspirin. Similarly, they make the natural painkiller morphine into diacetylmorphine, or heroin. | https://www.wikidoc.org/index.php/Acetyl | |
f2168fcf05b26bc16c4e2ecb1cdd62cc7a7ebf5d | wikidoc | Acinus | Acinus
An acinus (adjective: acinar, plural acini) refers to the berry-shaped termination of an exocrine gland, where the secretion is produced.
They are found in many organs, including:
- the stomach
- the sebaceous gland of the scalp
- the salivary glands of the tongue
- the liver
- the lacrimal glands
- the pancreas
Mucous acini usually stain pale, while serous acini usually stain dark.
The term "acinus" is considered synonymous with alveolus by some sources, but not all. | Acinus
Template:Infobox Anatomy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753
An acinus (adjective: acinar, plural acini) refers to the berry-shaped termination of an exocrine gland, where the secretion is produced.
They are found in many organs, including:
- the stomach[1]
- the sebaceous gland of the scalp
- the salivary glands of the tongue[2]
- the liver
- the lacrimal glands
- the pancreas [3]
Mucous acini usually stain pale, while serous acini usually stain dark.
The term "acinus" is considered synonymous with alveolus by some sources, but not all. | https://www.wikidoc.org/index.php/Acinar | |
50987b471036c5de9cb6569a4e1631b690155aa8 | wikidoc | Keloid | Keloid
# Overview
A keloid is a type of scar which results in an overgrowth of tissue at the site of a healed skin injury. Keloids are firm, rubbery lesions or shiny, fibrous nodules, and can vary from pink to flesh-colored or red to dark brown in color. A keloid scar is benign, non-contagious, and usually accompanied by severe itchiness, sharp pains, and changes in texture. In severe cases, it can affect movement of skin. Keloids should not be confused with hypertrophic scars, which are raised scars that do not grow beyond the boundaries of the original wound and may reduce over time.
# Occurrence
Keloids expand in claw-like growths over normal skin. They have the capability to hurt with a needle-like pain or to itch without warning, although the degree of sensation varies from patient to patient.
If the keloid becomes infected, it may ulcerate. The only treatment is to remove the scar completely. However, the probability that the resulting surgery scar will also become a keloid is high, usually greater than 50%.
Keloids form within scar tissue. Collagen, used in wound repair, tends to overgrow in this area, sometimes producing a lump many times larger than that of the original scar. Although they usually occur at the site of an injury, keloids can also arise spontaneously. They can occur at the site of a piercing and even from something as simple as a pimple or scratch. They can occur as a result of severe acne or chickenpox scarring, infection at a wound site, repeated trauma to an area, excessive skin tension during wound closure or a foreign body in a wound. Keloids can sometimes be sensitive to chlorine.
Keloids affect both sexes equally, although the incidence in young female patients has been reported to be higher than in young males, probably reflecting the greater frequency of earlobe piercing among women.
There is a fifteen times higher frequency of occurrence in highly pigmented people. It is speculated that people who possess any degree of African descent, regardless of skin color, may be especially susceptible to keloid occurrences.
# History in medicine
Keloids were described by Egyptian surgeons around 1700 BC. Baron Jean-Louis Alibert (1768-1837) identified the keloid as an entity in 1806. He called them cancroide, later changing the name to cheloide to avoid confusion with cancer. The word is derived from the Greek chele, meaning crab's claw, and the suffix -oid, meaning like. For many years Alibert's clinic at the L'Hôpital Saint-Louis was the world’s center for dermatology.
# Intentional keloids
The Olmec of Mexico in pre-Columbian times used keloid scarification as a means of decoration. In the modern era, women of the Nubia-Kush in Sudan are intentionally scarified with facial keloids as a means of decoration. The Nuer and Nuba use lip plugs, keloid tattoos along the forehead, keloid tattoos along the chin and above the lip, and cornrows. As a part of a ritual the people of Papua New Guinea cut their skin and insert clay or ash into the wounds so as to develop permanent bumps (known as keloids or weals). This painful ritual honors members of their tribe who are celebrated for their courage and endurance.
# Locations of keloids
Keloids are mostly found on earlobes, the sternum, shoulders, the upper back and any place where abrasion has occurred. These are usually the result of pimples, insect bites, scratching, burns, or other skin trauma.
Certain procedures are known to cause keloid formation such as within post-operative surgical scars or on earlobes following piercing and behind the ears after otoplasty.
# Incidence
People of all ages can develop a keloid. Children under 11 are less likely to develop keloids, even when they get their ears pierced. Keloids may also develop from pseudofoliculitis barbae, continued shaving when one has razor bumps will cause irritation to the bumps, infection and over time keloids will form. It would thus be wise for a man with razor bumps to stop shaving for a while and have the skin repair itself first before undertaking any form of hair removal.
# Diagnosis
## Physical Examination
### Ear
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
- Keloid. Adapted from Dermatology Atlas.
# Treatments
No treatment for keloids is considered to be 100% effective. Some of the treatments that are currently available are described below. These treatments have varying degrees of effectiveness. All the invasive methods of treatment like surgery carry a serious risk of the keloid recurring and becoming bigger than it previously was.
- Surgery — Surgery requires great care during and after the operation. Keloids that return after being excised may be larger than the original. There is a 50% chance of recurrence after surgical removal. However, keloids are less likely to return if surgical removal is combined with other treatments. Surgical or laser excision may be followed by intralesional injections of a corticosteroid. Plastic closure of the skin including techniques such as v-plasty or w-plasty to reduce skin tension are known to reduce recurrence of keloids following excision.
- Dressings — Moistened wound coverings made of silicone gel (such as Dermatix) or silastic have been shown in studies to reduce keloid prominence over time. This treatment is safe and painless, although some patients may experience increased itchiness from wearing the dressing for an extended period of time.
- Steroid injections — Steroid injections are best used as the scar begins to thicken or if the person is a known keloid former. A series of injections with triamcinolone acetonide or another corticosteroid may reduce keloid size and irritation. However, injections are often uncomfortable and in large and/or hard scars can be difficult to perform, requiring local anesthetic for people over 16, and full anesthetic for people under. The treatment area can become very painful as the anesthetic wears off.
- Compression — Compression bandages applied to the site over several months, sometimes for as long as six to twelve months, may lead to a reduction in the size of the keloid. This is the best treatment for preventing new scars.
- Cryosurgery — Cryosurgery is an excellent treatment for keloids which are small and occur on lightly pigmented skin. It is often combined with monthly cortisone injections. The use of cryotherapy is limited since it causes skin blanching. It freezes the skin and causes sludging of the circulation beneath, effectively creating an area of localized frostbite. There is a slough of skin and keloid with re-epithelization.
- Radiation therapy — Electron beam radiation can be used at levels which do not penetrate the body deeply enough to affect internal organs. Orthovoltage radiation is more penetrating and slightly more effective. Radiation treatments reduce scar formation if they are used soon after a surgery while the surgical wound is healing. This is one of the most effective procedures.
- Laser therapy — This is an alternative to conventional surgery for keloid removal. Lasers produce a superficial peel but often do not reduce the bulk of the keloid. The use of dye-tuned lasers has not shown better results than that of cold lasers.
- Newer treatments — Drugs that are used to treat autoimmune diseases or cancer have shown promise. These include alpha-interferon, 5-fluorouracil and bleomycin. However, there is a need for further study and evaluation of this treatment technique.
# Case presentation
This is a young male with bilateral keloid formation on the plantar surfaces of both feet. He has never been treated for this condition. There are other much smaller keloids located at small inlets on the glabrous(hairless) skin. | Keloid
Template:DiseaseDisorder infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]
# Overview
A keloid is a type of scar which results in an overgrowth of tissue at the site of a healed skin injury. Keloids are firm, rubbery lesions or shiny, fibrous nodules, and can vary from pink to flesh-colored or red to dark brown in color. A keloid scar is benign, non-contagious, and usually accompanied by severe itchiness, sharp pains, and changes in texture. In severe cases, it can affect movement of skin. Keloids should not be confused with hypertrophic scars, which are raised scars that do not grow beyond the boundaries of the original wound and may reduce over time.
# Occurrence
Keloids expand in claw-like growths over normal skin. They have the capability to hurt with a needle-like pain or to itch without warning, although the degree of sensation varies from patient to patient.
If the keloid becomes infected, it may ulcerate. The only treatment is to remove the scar completely. However, the probability that the resulting surgery scar will also become a keloid is high, usually greater than 50%.
Keloids form within scar tissue. Collagen, used in wound repair, tends to overgrow in this area, sometimes producing a lump many times larger than that of the original scar. Although they usually occur at the site of an injury, keloids can also arise spontaneously. They can occur at the site of a piercing and even from something as simple as a pimple or scratch. They can occur as a result of severe acne or chickenpox scarring, infection at a wound site, repeated trauma to an area, excessive skin tension during wound closure or a foreign body in a wound. Keloids can sometimes be sensitive to chlorine.
Keloids affect both sexes equally, although the incidence in young female patients has been reported to be higher than in young males, probably reflecting the greater frequency of earlobe piercing among women.
There is a fifteen times higher frequency of occurrence in highly pigmented people. It is speculated that people who possess any degree of African descent, regardless of skin color, may be especially susceptible to keloid occurrences.
# History in medicine
Keloids were described by Egyptian surgeons around 1700 BC. Baron Jean-Louis Alibert (1768-1837) identified the keloid as an entity in 1806. He called them cancroide, later changing the name to cheloide to avoid confusion with cancer. The word is derived from the Greek chele, meaning crab's claw, and the suffix -oid, meaning like. For many years Alibert's clinic at the L'Hôpital Saint-Louis was the world’s center for dermatology.
# Intentional keloids
The Olmec of Mexico in pre-Columbian times used keloid scarification as a means of decoration. In the modern era, women of the Nubia-Kush in Sudan are intentionally scarified with facial keloids as a means of decoration. The Nuer and Nuba use lip plugs, keloid tattoos along the forehead, keloid tattoos along the chin and above the lip, and cornrows. As a part of a ritual the people of Papua New Guinea cut their skin and insert clay or ash into the wounds so as to develop permanent bumps (known as keloids or weals). This painful ritual honors members of their tribe who are celebrated for their courage and endurance.
# Locations of keloids
Keloids are mostly found on earlobes, the sternum, shoulders, the upper back and any place where abrasion has occurred. These are usually the result of pimples, insect bites, scratching, burns, or other skin trauma.
Certain procedures are known to cause keloid formation such as within post-operative surgical scars or on earlobes following piercing and behind the ears after otoplasty.
# Incidence
People of all ages can develop a keloid. Children under 11 are less likely to develop keloids, even when they get their ears pierced. Keloids may also develop from pseudofoliculitis barbae, continued shaving when one has razor bumps will cause irritation to the bumps, infection and over time keloids will form. It would thus be wise for a man with razor bumps to stop shaving for a while and have the skin repair itself first before undertaking any form of hair removal.
# Diagnosis
## Physical Examination
### Ear
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
- Keloid. Adapted from Dermatology Atlas.[1]
# Treatments
No treatment for keloids is considered to be 100% effective. Some of the treatments that are currently available are described below. These treatments have varying degrees of effectiveness. All the invasive methods of treatment like surgery carry a serious risk of the keloid recurring and becoming bigger than it previously was.
- Surgery — Surgery requires great care during and after the operation. Keloids that return after being excised may be larger than the original. There is a 50% chance of recurrence after surgical removal. However, keloids are less likely to return if surgical removal is combined with other treatments. Surgical or laser excision may be followed by intralesional injections of a corticosteroid. Plastic closure of the skin including techniques such as v-plasty or w-plasty to reduce skin tension are known to reduce recurrence of keloids following excision.
- Dressings — Moistened wound coverings made of silicone gel (such as Dermatix) or silastic have been shown in studies to reduce keloid prominence over time. This treatment is safe and painless, although some patients may experience increased itchiness from wearing the dressing for an extended period of time.
- Steroid injections — Steroid injections are best used as the scar begins to thicken or if the person is a known keloid former. A series of injections with triamcinolone acetonide or another corticosteroid may reduce keloid size and irritation. However, injections are often uncomfortable and in large and/or hard scars can be difficult to perform, requiring local anesthetic for people over 16, and full anesthetic for people under. The treatment area can become very painful as the anesthetic wears off.
- Compression — Compression bandages applied to the site over several months, sometimes for as long as six to twelve months, may lead to a reduction in the size of the keloid. This is the best treatment for preventing new scars.
- Cryosurgery — Cryosurgery is an excellent treatment for keloids which are small and occur on lightly pigmented skin. It is often combined with monthly cortisone injections. The use of cryotherapy is limited since it causes skin blanching. It freezes the skin and causes sludging of the circulation beneath, effectively creating an area of localized frostbite. There is a slough of skin and keloid with re-epithelization.
- Radiation therapy — Electron beam radiation can be used at levels which do not penetrate the body deeply enough to affect internal organs. Orthovoltage radiation is more penetrating and slightly more effective. Radiation treatments reduce scar formation if they are used soon after a surgery while the surgical wound is healing. This is one of the most effective procedures.[2]
- Laser therapy — This is an alternative to conventional surgery for keloid removal. Lasers produce a superficial peel but often do not reduce the bulk of the keloid. The use of dye-tuned lasers has not shown better results than that of cold lasers.
- Newer treatments — Drugs that are used to treat autoimmune diseases or cancer have shown promise. These include alpha-interferon, 5-fluorouracil and bleomycin. However, there is a need for further study and evaluation of this treatment technique.
# Case presentation
This is a young male with bilateral keloid formation on the plantar surfaces of both feet. He has never been treated for this condition. There are other much smaller keloids located at small inlets on the glabrous(hairless) skin. | https://www.wikidoc.org/index.php/Acne_keloid | |
268715f8cc8a5648c4986287334016442d86bb1d | wikidoc | Xylene | Xylene
# Overview
The term xylenes refers to a group of 3 benzene derivatives which encompasses ortho-, meta-, and para- isomers of dimethyl benzene. The o-, m- and p- isomers specify to which carbon atoms (of the main benzene ring) the two methyl groups are attached. Counting the carbon atoms from one of the ring carbons bonded to a methyl group, and counting towards the second ring carbon bonded to a methyl group, the o- isomer has the IUPAC name of 1,2-dimethylbenzene. The m- isomer has the IUPAC name of 1,3-dimethylbenzene. And p- isomer has the IUPAC name of 1,4-dimethylbenzene.
It is a colorless, sweet-smelling liquid that is very flammable. It occurs naturally in petroleum and coal tar and is formed during forest fires. The chemical properties differ slightly from isomer to isomer. The melting point is between −47.87 °C (−54.17 °F) (m-xylene) and 13.26 °C (55.87 °F) (p-xylene). The boiling point is for each isomer at around 140 °C (284 °F). The density is at around 0.87 kg/L (7.26 lb/U.S. gallon or 8.72 lb/imp gallon) and thus is less dense than water. Xylene in air can be smelled at 0.08 to 3.7 parts of xylene per million parts of air (ppm) and can begin to be tasted in water at 0.53 to 1.8 ppm.
Chemical industries produce xylene from petroleum. It is one of the top 30 chemicals produced in the United States in terms of volume. Xylene is used as a solvent and in the printing, rubber, and leather industries. p-Xylene is used as a feedstock in the production of terephthalic acid, which is a monomer used in the production of polymers. It is also used as a cleaning agent for steel and for silicon wafers and chips, a pesticide , a thinner for paint, and in paints and varnishes. It may be substituted for toluene to thin lacquers where slower drying is desired. It is found in small amounts in airplane fuel and gasoline. In animal studies it is often swabbed on the ears of rabbits to facilitate blood flow and collection, although the area must subsequently be cleansed with alcohol to prevent inflammation.
# Related compounds
Xylenes are a starting material for the production of other chemicals. For instance chlorination gives a xylylene dichlorides or 1,2-bis(chloromethyl)benzene (again three possible isomers). With oxidizing agents, such as potassium permanganate (KMnO4), the methyl group can be oxidized to a carboxylic acid. By oxidizing both methyl groups towards the acid, o-xylene forms phthalic acid, whereas p-xylene forms terephthalic acid.
# Health effects
Xylene affects the brain. High levels from exposure for short periods (14 days or less) or long periods (more than 1 year) can cause headaches, lack of muscle coordination, dizziness, confusion, and changes in one's sense of balance. Exposure of people to high levels of xylene for short periods can also cause irritation of the skin, eyes, nose, and throat; difficulty in breathing; problems with the lungs; delayed reaction time; memory difficulties; stomach discomfort; and possibly changes in the liver and kidneys. It can cause unconsciousness and even death at very high levels (see inhalants).
Studies of unborn animals indicate that high concentrations of xylene may cause increased numbers of deaths, and delayed growth and development. In many instances, these same concentrations also cause damage to the mothers. It is not yet known whether xylene harms the unborn fetus if the mother is exposed to low levels of xylene during pregnancy.
Besides occupational exposure, the principal pathway of human contact is via soil contamination from leaking underground storage tanks containing petroleum products. Humans who come into contact with the soil or groundwater may become affected. Use of contaminated groundwater as a water supply could lead to adverse health effects.
Another common form of human exposure to xylene is in the use of certain types of pens, writing and drawing instruments, bingo dabbers and art supplies. | Xylene
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
The term xylenes refers to a group of 3 benzene derivatives which encompasses ortho-, meta-, and para- isomers of dimethyl benzene. The o-, m- and p- isomers specify to which carbon atoms (of the main benzene ring) the two methyl groups are attached. Counting the carbon atoms from one of the ring carbons bonded to a methyl group, and counting towards the second ring carbon bonded to a methyl group, the o- isomer has the IUPAC name of 1,2-dimethylbenzene. The m- isomer has the IUPAC name of 1,3-dimethylbenzene. And p- isomer has the IUPAC name of 1,4-dimethylbenzene.
It is a colorless, sweet-smelling liquid that is very flammable. It occurs naturally in petroleum and coal tar and is formed during forest fires. The chemical properties differ slightly from isomer to isomer. The melting point is between −47.87 °C (−54.17 °F) (m-xylene) and 13.26 °C (55.87 °F) (p-xylene). The boiling point is for each isomer at around 140 °C (284 °F). The density is at around 0.87 kg/L (7.26 lb/U.S. gallon or 8.72 lb/imp gallon) and thus is less dense than water. Xylene in air can be smelled at 0.08 to 3.7 parts of xylene per million parts of air (ppm) and can begin to be tasted in water at 0.53 to 1.8 ppm.
Chemical industries produce xylene from petroleum. It is one of the top 30 chemicals produced in the United States in terms of volume. Xylene is used as a solvent and in the printing, rubber, and leather industries. p-Xylene is used as a feedstock in the production of terephthalic acid, which is a monomer used in the production of polymers. It is also used as a cleaning agent for steel and for silicon wafers and chips, a pesticide [2], a thinner for paint, and in paints and varnishes. It may be substituted for toluene to thin lacquers where slower drying is desired. It is found in small amounts in airplane fuel and gasoline. In animal studies it is often swabbed on the ears of rabbits to facilitate blood flow and collection, although the area must subsequently be cleansed with alcohol to prevent inflammation.
# Related compounds
Xylenes are a starting material for the production of other chemicals. For instance chlorination gives a xylylene dichlorides or 1,2-bis(chloromethyl)benzene (again three possible isomers). With oxidizing agents, such as potassium permanganate (KMnO4), the methyl group can be oxidized to a carboxylic acid. By oxidizing both methyl groups towards the acid, o-xylene forms phthalic acid, whereas p-xylene forms terephthalic acid.
# Health effects
Xylene affects the brain. High levels from exposure for short periods (14 days or less) or long periods (more than 1 year) can cause headaches, lack of muscle coordination, dizziness, confusion, and changes in one's sense of balance. Exposure of people to high levels of xylene for short periods can also cause irritation of the skin, eyes, nose, and throat; difficulty in breathing; problems with the lungs; delayed reaction time; memory difficulties; stomach discomfort; and possibly changes in the liver and kidneys. It can cause unconsciousness and even death at very high levels (see inhalants).
Studies of unborn animals indicate that high concentrations of xylene may cause increased numbers of deaths, and delayed growth and development. In many instances, these same concentrations also cause damage to the mothers. It is not yet known whether xylene harms the unborn fetus if the mother is exposed to low levels of xylene during pregnancy.
Besides occupational exposure, the principal pathway of human contact is via soil contamination from leaking underground storage tanks containing petroleum products. Humans who come into contact with the soil or groundwater may become affected. Use of contaminated groundwater as a water supply could lead to adverse health effects.
Another common form of human exposure to xylene is in the use of certain types of pens, writing and drawing instruments, bingo dabbers and art supplies. | https://www.wikidoc.org/index.php/Acute_xylene_poisoning | |
6cabec3b82a2c86e191694e2917be26d157b8833 | wikidoc | Videos | Videos
# How to Insert an YouTube Video
- Log on to YouTube
- Upload your video onto YouTube
- Look at the url of your video that you uploaded, you can find it on the right hand side of the page on YouTube, an example would be
- Enter the exact letters and numbers in the web address on the YouTube to your WikiDoc page using the code listed below. Thats is all you need to do to insert a video.
You type what is in the box (Make sure you put a space between the word youtube and the v or it wont work):
This is what plays:
# How to Insert A Twitter Video
- Step 1: Copy the web address of the tweet that contains the video (For example: ).
- Step 2: Replace the url in the following syntax with the web address.
- Step 3: The video will be displayed as follows: | Videos
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# How to Insert an YouTube Video
- Log on to YouTube
- Upload your video onto YouTube
- Look at the url of your video that you uploaded, you can find it on the right hand side of the page on YouTube, an example would be http://www.youtube.com/watch?v=7TWu0_Gklzo
- Enter the exact letters and numbers in the web address on the YouTube to your WikiDoc page using the code listed below. Thats is all you need to do to insert a video.
You type what is in the box (Make sure you put a space between the word youtube and the v or it wont work):
This is what plays:
# How to Insert A Twitter Video
- Step 1: Copy the web address of the tweet that contains the video (For example: https://twitter.com/WHO/status/865112913924808704).
- Step 2: Replace the url in the following syntax with the web address.
- Step 3: The video will be displayed as follows:
<a href="https://twitter.com/WHO/status/865112913924808704"></a> | https://www.wikidoc.org/index.php/Adding_Video | |
6deabdabca592d438efd65b752055499ba31c0d9 | wikidoc | Audios | Audios
# Overview
There is the capacity to insert audio files (such as heart murmurs) into the contents of chapters.
# Audio File Formats That Are Supported
Both the .mp3 and .ogg file formats are supported.
# Resources to Convert Your Audio Files into MP3 Format
There are variety of free software programs on the internet available to convert audio files into it and MP3 format such as
# Uploading Media
The link to upload your audio file is here.
# Code to Insert Your Audio File
The wiki code to insert your audio file looks something like this:
# Example
Below is the code to play the sounds of a murmur associated with a VSD:
If you type the following code:
This is what appears:
VSD Murmur | Audios
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
There is the capacity to insert audio files (such as heart murmurs) into the contents of chapters.
# Audio File Formats That Are Supported
Both the .mp3 and .ogg file formats are supported.
# Resources to Convert Your Audio Files into MP3 Format
There are variety of free software programs on the internet available to convert audio files into it and MP3 format such as[2]
# Uploading Media
The link to upload your audio file is here.
# Code to Insert Your Audio File
The wiki code to insert your audio file looks something like this:
[[Media:your file name.mp3|Name of the sound]]
# Example
Below is the code to play the sounds of a murmur associated with a VSD:
If you type the following code:
[[Media:VSD murmur.mp3|VSD Murmur]]
This is what appears:
VSD Murmur | https://www.wikidoc.org/index.php/Adding_audios | |
1c2a5c45924b9d2bbd65421022407fdfce1f9bf7 | wikidoc | Adduct | Adduct
An adduct (from the Latin adductus, "drawn toward") is a product of a direct addition of two or more distinct molecules, resulting in a single reaction product containing all atoms of all components, with formation of two chemical bonds and a net reduction in bond multiplicity in at least one of the reactants. The resultant is considered a distinct molecular species. Examples include the adduct between hydrogen peroxide and sodium carbonate to give sodium percarbonate, and the addition of sodium bisulfite to an aldehyde to give a sulfonate.
Adducts often form between Lewis acids and Lewis bases. A good example would be the formation of adducts between the Lewis acid borane and the oxygen atom in the Lewis bases, tetrahydrofuran (THF) or diethyl ether: BH3THF, BH3OEt2.
Adducts are not necessarily molecular in nature. A good example from solid-state chemistry are the adducts of ethylene or carbon monoxide of CuAlCl4. The latter is a solid with an extended lattice structure. Upon formation of the adduct a new extended phase is formed in which the gas molecules are incorporated (inserted) as ligands of the copper atoms within the structure. This reaction can also be considered a reaction between a base and a Lewis acid with the copper atom in the electron-receiving and the pi-electrons of the gas molecule in the donating role. | Adduct
An adduct (from the Latin adductus, "drawn toward") is a product of a direct addition of two or more distinct molecules, resulting in a single reaction product containing all atoms of all components, with formation of two chemical bonds and a net reduction in bond multiplicity in at least one of the reactants. The resultant is considered a distinct molecular species. Examples include the adduct between hydrogen peroxide and sodium carbonate to give sodium percarbonate, and the addition of sodium bisulfite to an aldehyde to give a sulfonate.
Adducts often form between Lewis acids and Lewis bases. A good example would be the formation of adducts between the Lewis acid borane and the oxygen atom in the Lewis bases, tetrahydrofuran (THF) or diethyl ether: BH3•THF, BH3•OEt2.
Adducts are not necessarily molecular in nature. A good example from solid-state chemistry are the adducts of ethylene or carbon monoxide of CuAlCl4. The latter is a solid with an extended lattice structure. Upon formation of the adduct a new extended phase is formed in which the gas molecules are incorporated (inserted) as ligands of the copper atoms within the structure. This reaction can also be considered a reaction between a base and a Lewis acid with the copper atom in the electron-receiving and the pi-electrons of the gas molecule in the donating role.[1] | https://www.wikidoc.org/index.php/Adduct | |
4860b7182105ecd11da8a5f92659f8399521420a | wikidoc | Ageing | Ageing
Synonyms and keywords: Aging
# Overview
Ageing is any change in an organism over time. Ageing refers to a multidimensional process of physical, psychological, and social change. Some dimensions of aging grow and expand over time, while others decline. Reaction time, for example, may slow with age, while knowledge of world events and wisdom may expand. Research shows that even late in life potential exists for physical, mental, and social growth and development. Aging is an important part of all human societies reflecting the biological changes that occur, but also reflecting cultural and societal conventions. Age is usually measured in full years — and months for young children. A person's birthday is often an important event.
The term "aging" is somewhat ambiguous. Distinctions may be made between "universal aging" (age changes that all people share) and "probabilistic aging" (age changes that may happen to some, but not all people as they grow older, such as the onset of Type Two diabetes). Chronological aging, referring to how old a person is, is arguably the most straightforward definition of aging and may be distinguished from "social aging" (society's expectations of how people should act as they grow older) and "biological aging" (an organism's physical state as it ages). There is also a distinction between "proximal aging" (age-based effects that come about because of factors in the recent past) and "distal aging" (age-based differences that can be traced back to a cause early in person's life, such as childhood poliomyelitis).
Differences are sometimes made between populations of children;divisions are sometimes made between the young old (65-74), the middle old (75-84) and the oldest old (those aged 85 and above). However, problematic in this is that chronological age does not correlate perfectly with functional age, i.e. two people may be of the same age, but differ in their mental and physical capacities.
Population aging is the increase in the number and proportion of older people in society. Population aging has three possible causes: migration, longer life expectancy (decreased death rate), and decreased birth rate. Aging has a significant impact on society. Young people tend to commit most crimes, they are more likely to push for political and social change, to develop and adopt new technologies, and to need education. Older people have different requirements from society and government as opposed to young people, and frequently differing values as well. Older people are also far more likely to vote, and in many countries the young are forbidden from voting. Thus, the aged have comparatively more political influence.
# Senescence
In biology, senescence is the state or process of aging. Cellular senescence is a phenomenon where isolated cells demonstrate a limited ability to divide in culture (the Hayflick Limit, discovered by Leonard Hayflick in 1965), while Organismal senescence is the aging of organisms.
After a period of near perfect renewal (in humans, between 20 and 35 years of age), organismal senescence is characterized by the declining ability to respond to stress, increasing homeostatic imbalance and increased risk of disease. This irreversible series of changes inevitably ends in death.
Some researchers (specifically biogerontologists) are treating aging as a disease. As genes that have an effect on aging are discovered, aging is increasingly being regarded in a similar fashion to other genetic conditions, potentially "treatable."
Indeed, aging is not an unavoidable property of life. Instead, it is the result of a genetic program. Numerous species show very low signs of aging ("negligible senescence'), the best known being trees like the bristlecone pine, fish like the sturgeon and the rockfish, invertebrates like the quahog or sea anemone .
In humans and other animals, cellular senescence has been attributed to the shortening of telomeres with each cell cycle; when telomeres become too short, the cells die. The length of telomeres is therefore the "molecular clock," predicted by Hayflick. Telomere length is maintained in immortal cells (e.g. germ cells and keratinocyte stem cells, but not other skin cell types) by the enzyme telomerase. In the laboratory, mortal cell lines can be immortalized by the activation of their telomerase gene, present in all cells but active in few cell types. Cancerous cells must become immortal to multiply without limit. This important step towards carcinogenesis implies, in 85% of cancers, the reactivation of their telomerase gene by mutation. Since this mutation is rare, the telomere "clock" can be seen as a protective mechanism against cancer .
Other genes are known to affect the aging process, the sirtuin family of genes have been shown to have a significant effect on the lifespan of yeast and nematodes. Over-expression of the RAS2 gene increases lifespan in yeast substantially.
In addition to genetic ties to lifespan, diet has been shown to substantially affect lifespan in many animals. Specifically, caloric restriction (that is, restricting calories to 30-50% less than an ad libitum animal would consume, while still maintaining proper nutrient intake), has been shown to increase lifespan in mice up to 50%. Caloric restriction works on many other species beyond mice (including species as diverse as yeast and Drosophila), and appears (though the data is not conclusive) to increase lifespan in primates according to a study done on Rhesus monkeys at the National Institute of Health (US). Since, at the molecular level, age is counted not as time but as the number of cell doublings, this effect of calorie reduction could be mediated by the slowing of cellular growth and, therefore, the lengthening of the time between cell divisions.
Drug companies are currently searching for ways to mimic the lifespan-extending effects of caloric restriction without having to severely reduce food consumption.
# Dividing the Lifespan
A human life is often divided into various ages. Historically, the lifespan of man was divided into seven ages; because biological changes are slow moving and vary from person to person, arbitrary dates are usually set to mark periods of human life. In some cultures the divisions given below are quite varied.
In the USA, adulthood legally begins at the age of eighteen or nineteen, while old age is considered to begin at the age of legal retirement (approximately 65).
- Pre-conception: ovum, spermatozoon, possible pre-existence
- Conception: fertilization
- Pre-birth: conception to birth
- Infancy: Birth to 2
- Childhood: 2 to 11
- Adolescence: 12 to 19
- Early adulthood: 20 to 35
- Middle adulthood: 35 to 54
- Late adulthood: 55+
- Death
- Post-Death: Decomposition
Ages can also be divided by decade:
- Denarian: someone between 10 and 19 years of age
- Vicenarian: someone between 20 and 29 years of age
- Tricenarian: someone between 30 and 39 years of age
- Quadragenarian: someone between 40 and 49 years of age
- Quinquagenarian: someone between 50 and 59 years of age
- Sexagenarian: someone between 60 and 69 years of age
- Septuagenarian: someone between 70 and 79 years of age
- Octogenarian: someone between 80 and 89 years of age
- Nonagenarian: someone between 90 and 99 years of age
- Centenarian: someone over 100 years of age
- Supercentenarian: someone over 110 years of age
# Cultural Variations
In some cultures (for example Serbian and Russian) there are two ways to express age: by counting years with or without including current year. For example, it could be said about the same person that he is twenty years old or that he is in twenty-first year of his life. In Russian the former expression is generally used, the latter one has restricted usage: it is used for age of a deceased person in obituaries and for age of a child when it is desired to show him/her older than he/she is. (It seems that a boy in his 4th year is older than one who is 3 years old.)
Considerable numbers of cultures have less of a problem with age compared with what has been described above, and it is seen as an important status to reach stages in life, rather than defined numerical ages. Advanced age is given more respect and status.
East Asian age reckoning is different from that found in Western culture. Traditional Chinese culture uses a different aging method, called Xusui (虛歲) with respect to common aging which is called Zhousui (周歲). In the Xusui method, people are born at age 1, not age 0.
# Society
## Legal
There are variations in many countries as to what age a person legally becomes an adult.
Most legal systems define a specific age for when an individual is allowed or obliged to do something. These ages include voting age, drinking age, age of consent, age of majority, age of criminal responsibility, marriageable age, age where one can hold public office, and mandatory retirement age. Admission to a movie for instance, may depend on age according to a motion picture rating system. A bus fare might be discounted for the young or old.
Similarly in many countries in jurisprudence, the defense of infancy is a form of defense by which a defendant argues that, at the time a law was broken, they were not liable for their actions, and thus should not be held liable for a crime. Many courts recognize that defendants who are considered to be juveniles may avoid criminal prosecution on account of their age.
## Economics and Marketing
The economics of aging are also of great import. Children and teenagers have little money of their own, but most of it is available for buying consumer goods. They also have considerable impact on how their parents spend money.
Young adults are an even more valuable cohort. They often have jobs with few responsibilities such as a mortgage or children. They do not yet have set buying habits and are more open to new products.
The young are thus the central target of marketers. Television is programmed to attract the range of 15 to 35 year olds. Movies are also built around appealing to the young.
## Health Care Demand
Many societies in the rich world, e.g. Western Europe and Japan, have aging populations. While the effects on society are complex, there is a concern about the impact on health care demand. The large number of suggestions in the literature for specific interventions to cope with the expected increase in demand for long-term care in aging societies can be organized under four headings: improve system performance; redesign service delivery; support informal caregivers; and shift demographic parameters.
However, the annual growth in national health spending is not mainly due to increasing demand from aging populations, but rather has been driven by rising incomes, costly new medical technology, a shortage of health care workers and informational asymmetries between providers and patients.
Even so, it has been estimated that population aging only explains 0.2 percentage points of the annual growth rate in medical spending of 4.3 percent since 1970. In addition, certain reforms to Medicare decreased elderly spending on home health care by 12.5 percent per year between 1996 and 2000. This would suggest that the impact of aging populations on health care costs is not inevitable.
## Impact on Prisons
As of July 2007, medical costs for a typical inmate might run an agency around $33 per day, while costs for an aging inmate could run upwards of $100. Most DOCs report spending more than 10 percent of the annual budget on elderly care. That is expected to rise over the next 10-20 years. Some states have talked about releasing aging inmates early.
# Cognitive Effects
Steady decline in many cognitive processes are seen across the lifespan, starting in one's thirties. Research has focused in particular on memory and aging, and has found decline in many types of memory with aging, but not in semantic memory or general knowledge such as vocabulary definitions, which typically increases or remains steady. Early studies on changes in cognition with age generally found declines in intelligence in the elderly, but studies were cross-sectional rather than longitudinal and thus results may be an artefact of cohort rather than a true example of decline. Intelligence may decline with age, though the rate may vary depending on the type, and may in fact remain steady throughout most of the lifespan, dropping suddenly only as people near the end of their lives. Individual variations in rate of cognitive decline may therefore be explained in terms of people having different lengths of life.
# Coping and Well-being
Psychologists have examined coping skills in the elderly. Various factors, such as social support, religion and spirituality, active engagement with life and having an internal locus of control have been proposed as being beneficial in helping people to cope with stressful life events in later life. Social support and personal control are possibly the two most important factors that predict well-being, morbidity and mortality in adults. Other factors that may link to well-being and quality of life in the elderly include social relationships (possibly relationships with pets as well as humans), and health.
Individuals in different wings in the same retirement home have demonstrated a lower risk of mortality and higher alertness and self-rated health in the wing where residents had greater control over their environment, though personal control may have less impact on specific measures of health. Social control, perceptions of how much influence one has over one's social relationships, shows support as a moderator variable for the relationship between social support and perceived health in the elderly, and may positively influence coping in the elderly.
## Religion
Religion has been an important factor used by the elderly in coping with the demands of later life, and appears more often than other forms of coping later in life. Religious commitment may also be associated with reduced mortality, though religiosity is a multidimensional variable; while participation in religious activities in the sense of participation in formal and organized rituals may decline, it may become a more informal, but still important aspect of life such as through personal or private prayer.
## Self-rated Health
Self-ratings of health, the beliefs in one's own health as excellent, fair or poor, has been correlated with well-being and mortality in the elderly; positive ratings are linked to high well-being and reduced mortality. Various reasons have been proposed for this association; people who are objectively healthy may naturally rate their health better than that of their ill counterparts, though this link has been observed even in studies which have controlled for socioeconomic status, psychological functioning and health status. This finding is generally stronger for men than women, though the pattern between genders is not universal across all studies, and some results suggest sex-based differences only appear in certain age groups, for certain causes of mortality and within a specific sub-set of self-ratings of health.
## Retirement
Retirement, a common transition faced by the elderly, may have both positive and negative consequences.
# Societal Impact
Societal aging refers to the demographic aging of populations and societies. Cultural differences in attitudes to aging have been studied.
## Emotional Improvement
Given the physical and cognitive declines seen in aging, a surprising finding is that emotional experience improves with age. Older adults are better at regulating their emotions and experience negative affect less frequently than younger adults and show a positivity effect in their attention and memory. The emotional improvements show up in longitudinal studies as well as in cross-sectional studies, and so cannot be entirely due to only the happier individuals surviving.
# Terminology
The concept of successful aging can be traced back to the 1950s, and popularised in the 1980s. Previous research into aging exaggerated the extent to which health disabilities, such as diabetes or osteoporosis, could be attributed exclusively to age, and research in gerontology exaggerated the homogeneity of samples of elderly people.
Successful aging consists of three components:
- Low probability of disease or disability;
- High cognitive and physical function capacity;
- Active engagement with life.
A greater number of people self-report successful aging than those that strictly meet these criteria.
Successful aging may be viewed an interdisciplinary concept, spanning both psychology and sociology, where it is seen as the transaction between society and individuals across the life span with specific focus on the later years of life. The terms "healthy aging" "optimal aging" have been proposed as alternatives to successful aging.
Six suggested dimensions of successful aging include:
- No physical disability over the age of 75 as rated by a physician;
- Good subjective health assessment (i.e. good self-ratings of one's health);
- Length of undisabled life;
- Good mental health;
- Objective social support;
- Self-rated life satisfaction in eight domains, namely marriage, income-related work, children, friendship and social contacts, hobbies, community service activities, religion and recreation/sports
# Theories
## Non-biological Theories
- Selectivity Theory - mediates between Activity and Disengagement Theory, which suggests that it may benefit older people to become more active in some aspects of their lives, more disengaged in others.
## Biological Theories
# Measure of Age
The normal point of time from where to measure the age of a human being is from birth. Age in prenatal development is normally measured in gestational age, taking the last menstruation of the woman as a point of beginning. Alternatively,fertilization age, beginning from fertilization can be taken.
Age is often rounded downward to an integer, where the time of birth is taken to have been 0:00 (in other words, the number of days is first rounded upward, before rounding downward to whole years). Thus the age range 4-11 is until the 12th birthday.
# Related Chapters
- Aging brain
- Biodemography
- Biological immortality
- Calorie restriction
- Gerontology
- Life expectancy
- List of life extension-related topics
- Longevity
- Maturity (psychological)
- Memory and aging
- Michael Ristow
- Mitohormesis
- Population aging
- Retirement
- Senescence
- The Grim Reaper Gene
- Youth bulge | Ageing
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Aging
# Overview
Ageing is any change in an organism over time. Ageing refers to a multidimensional process of physical, psychological, and social change. Some dimensions of aging grow and expand over time, while others decline. Reaction time, for example, may slow with age, while knowledge of world events and wisdom may expand. Research shows that even late in life potential exists for physical, mental, and social growth and development. Aging is an important part of all human societies reflecting the biological changes that occur, but also reflecting cultural and societal conventions. Age is usually measured in full years — and months for young children. A person's birthday is often an important event.
The term "aging" is somewhat ambiguous. Distinctions may be made between "universal aging" (age changes that all people share) and "probabilistic aging" (age changes that may happen to some, but not all people as they grow older, such as the onset of Type Two diabetes). Chronological aging, referring to how old a person is, is arguably the most straightforward definition of aging and may be distinguished from "social aging" (society's expectations of how people should act as they grow older) and "biological aging" (an organism's physical state as it ages). There is also a distinction between "proximal aging" (age-based effects that come about because of factors in the recent past) and "distal aging" (age-based differences that can be traced back to a cause early in person's life, such as childhood poliomyelitis).[1]
Differences are sometimes made between populations of children;divisions are sometimes made between the young old (65-74), the middle old (75-84) and the oldest old (those aged 85 and above). However, problematic in this is that chronological age does not correlate perfectly with functional age, i.e. two people may be of the same age, but differ in their mental and physical capacities.
Population aging is the increase in the number and proportion of older people in society. Population aging has three possible causes: migration, longer life expectancy (decreased death rate), and decreased birth rate. Aging has a significant impact on society. Young people tend to commit most crimes, they are more likely to push for political and social change, to develop and adopt new technologies, and to need education. Older people have different requirements from society and government as opposed to young people, and frequently differing values as well. Older people are also far more likely to vote, and in many countries the young are forbidden from voting. Thus, the aged have comparatively more political influence.
# Senescence
In biology, senescence is the state or process of aging. Cellular senescence is a phenomenon where isolated cells demonstrate a limited ability to divide in culture (the Hayflick Limit, discovered by Leonard Hayflick in 1965), while Organismal senescence is the aging of organisms.
After a period of near perfect renewal (in humans, between 20 and 35 years of age), organismal senescence is characterized by the declining ability to respond to stress, increasing homeostatic imbalance and increased risk of disease. This irreversible series of changes inevitably ends in death.
Some researchers (specifically biogerontologists) are treating aging as a disease. As genes that have an effect on aging are discovered, aging is increasingly being regarded in a similar fashion to other genetic conditions, potentially "treatable."
Indeed, aging is not an unavoidable property of life. Instead, it is the result of a genetic program. Numerous species show very low signs of aging ("negligible senescence'), the best known being trees like the bristlecone pine, fish like the sturgeon and the rockfish, invertebrates like the quahog or sea anemone [2].
In humans and other animals, cellular senescence has been attributed to the shortening of telomeres with each cell cycle; when telomeres become too short, the cells die. The length of telomeres is therefore the "molecular clock," predicted by Hayflick. Telomere length is maintained in immortal cells (e.g. germ cells and keratinocyte stem cells, but not other skin cell types) by the enzyme telomerase. In the laboratory, mortal cell lines can be immortalized by the activation of their telomerase gene, present in all cells but active in few cell types. Cancerous cells must become immortal to multiply without limit. This important step towards carcinogenesis implies, in 85% of cancers, the reactivation of their telomerase gene by mutation. Since this mutation is rare, the telomere "clock" can be seen as a protective mechanism against cancer [3].
Other genes are known to affect the aging process, the sirtuin family of genes have been shown to have a significant effect on the lifespan of yeast and nematodes. Over-expression of the RAS2 gene increases lifespan in yeast substantially.
In addition to genetic ties to lifespan, diet has been shown to substantially affect lifespan in many animals. Specifically, caloric restriction (that is, restricting calories to 30-50% less than an ad libitum animal would consume, while still maintaining proper nutrient intake), has been shown to increase lifespan in mice up to 50%. Caloric restriction works on many other species beyond mice (including species as diverse as yeast and Drosophila), and appears (though the data is not conclusive) to increase lifespan in primates according to a study done on Rhesus monkeys at the National Institute of Health (US). Since, at the molecular level, age is counted not as time but as the number of cell doublings, this effect of calorie reduction could be mediated by the slowing of cellular growth and, therefore, the lengthening of the time between cell divisions.
Drug companies are currently searching for ways to mimic the lifespan-extending effects of caloric restriction without having to severely reduce food consumption.
# Dividing the Lifespan
A human life is often divided into various ages. Historically, the lifespan of man was divided into seven ages; because biological changes are slow moving and vary from person to person, arbitrary dates are usually set to mark periods of human life. In some cultures the divisions given below are quite varied.
In the USA, adulthood legally begins at the age of eighteen or nineteen, while old age is considered to begin at the age of legal retirement (approximately 65).
- Pre-conception: ovum, spermatozoon, possible pre-existence
- Conception: fertilization
- Pre-birth: conception to birth
- Infancy: Birth to 2
- Childhood: 2 to 11
- Adolescence: 12 to 19
- Early adulthood: 20 to 35
- Middle adulthood: 35 to 54
- Late adulthood: 55+
- Death
- Post-Death: Decomposition
Ages can also be divided by decade:
- Denarian: someone between 10 and 19 years of age
- Vicenarian: someone between 20 and 29 years of age
- Tricenarian: someone between 30 and 39 years of age
- Quadragenarian: someone between 40 and 49 years of age
- Quinquagenarian: someone between 50 and 59 years of age
- Sexagenarian: someone between 60 and 69 years of age
- Septuagenarian: someone between 70 and 79 years of age
- Octogenarian: someone between 80 and 89 years of age
- Nonagenarian: someone between 90 and 99 years of age
- Centenarian: someone over 100 years of age
- Supercentenarian: someone over 110 years of age
# Cultural Variations
In some cultures (for example Serbian and Russian) there are two ways to express age: by counting years with or without including current year. For example, it could be said about the same person that he is twenty years old or that he is in twenty-first year of his life. In Russian the former expression is generally used, the latter one has restricted usage: it is used for age of a deceased person in obituaries and for age of a child when it is desired to show him/her older than he/she is. (It seems that a boy in his 4th year is older than one who is 3 years old.)
Considerable numbers of cultures have less of a problem with age compared with what has been described above, and it is seen as an important status to reach stages in life, rather than defined numerical ages. Advanced age is given more respect and status.
East Asian age reckoning is different from that found in Western culture. Traditional Chinese culture uses a different aging method, called Xusui (虛歲) with respect to common aging which is called Zhousui (周歲). In the Xusui method, people are born at age 1, not age 0.
# Society
## Legal
There are variations in many countries as to what age a person legally becomes an adult.
Most legal systems define a specific age for when an individual is allowed or obliged to do something. These ages include voting age, drinking age, age of consent, age of majority, age of criminal responsibility, marriageable age, age where one can hold public office, and mandatory retirement age. Admission to a movie for instance, may depend on age according to a motion picture rating system. A bus fare might be discounted for the young or old.
Similarly in many countries in jurisprudence, the defense of infancy is a form of defense by which a defendant argues that, at the time a law was broken, they were not liable for their actions, and thus should not be held liable for a crime. Many courts recognize that defendants who are considered to be juveniles may avoid criminal prosecution on account of their age.
## Economics and Marketing
The economics of aging are also of great import. Children and teenagers have little money of their own, but most of it is available for buying consumer goods. They also have considerable impact on how their parents spend money.
Young adults are an even more valuable cohort. They often have jobs with few responsibilities such as a mortgage or children. They do not yet have set buying habits and are more open to new products.
The young are thus the central target of marketers.[4] Television is programmed to attract the range of 15 to 35 year olds. Movies are also built around appealing to the young.
## Health Care Demand
Many societies in the rich world, e.g. Western Europe and Japan, have aging populations. While the effects on society are complex, there is a concern about the impact on health care demand. The large number of suggestions in the literature for specific interventions to cope with the expected increase in demand for long-term care in aging societies can be organized under four headings: improve system performance; redesign service delivery; support informal caregivers; and shift demographic parameters.[5]
However, the annual growth in national health spending is not mainly due to increasing demand from aging populations, but rather has been driven by rising incomes, costly new medical technology, a shortage of health care workers and informational asymmetries between providers and patients.[6]
Even so, it has been estimated that population aging only explains 0.2 percentage points of the annual growth rate in medical spending of 4.3 percent since 1970. In addition, certain reforms to Medicare decreased elderly spending on home health care by 12.5 percent per year between 1996 and 2000. [7] This would suggest that the impact of aging populations on health care costs is not inevitable.
## Impact on Prisons
As of July 2007, medical costs for a typical inmate might run an agency around $33 per day, while costs for an aging inmate could run upwards of $100. Most DOCs report spending more than 10 percent of the annual budget on elderly care. That is expected to rise over the next 10-20 years. Some states have talked about releasing aging inmates early. [8]
# Cognitive Effects
Steady decline in many cognitive processes are seen across the lifespan, starting in one's thirties. Research has focused in particular on memory and aging, and has found decline in many types of memory with aging, but not in semantic memory or general knowledge such as vocabulary definitions, which typically increases or remains steady. Early studies on changes in cognition with age generally found declines in intelligence in the elderly, but studies were cross-sectional rather than longitudinal and thus results may be an artefact of cohort rather than a true example of decline. Intelligence may decline with age, though the rate may vary depending on the type, and may in fact remain steady throughout most of the lifespan, dropping suddenly only as people near the end of their lives. Individual variations in rate of cognitive decline may therefore be explained in terms of people having different lengths of life.[1]
# Coping and Well-being
Psychologists have examined coping skills in the elderly. Various factors, such as social support, religion and spirituality, active engagement with life and having an internal locus of control have been proposed as being beneficial in helping people to cope with stressful life events in later life.[9][10][11] Social support and personal control are possibly the two most important factors that predict well-being, morbidity and mortality in adults.[12] Other factors that may link to well-being and quality of life in the elderly include social relationships (possibly relationships with pets as well as humans), and health.[13]
Individuals in different wings in the same retirement home have demonstrated a lower risk of mortality and higher alertness and self-rated health in the wing where residents had greater control over their environment,[14][15] though personal control may have less impact on specific measures of health.[11] Social control, perceptions of how much influence one has over one's social relationships, shows support as a moderator variable for the relationship between social support and perceived health in the elderly, and may positively influence coping in the elderly.[16]
## Religion
Religion has been an important factor used by the elderly in coping with the demands of later life, and appears more often than other forms of coping later in life.[17] Religious commitment may also be associated with reduced mortality, though religiosity is a multidimensional variable; while participation in religious activities in the sense of participation in formal and organized rituals may decline, it may become a more informal, but still important aspect of life such as through personal or private prayer.[18]
## Self-rated Health
Self-ratings of health, the beliefs in one's own health as excellent, fair or poor, has been correlated with well-being and mortality in the elderly; positive ratings are linked to high well-being and reduced mortality.[19][20] Various reasons have been proposed for this association; people who are objectively healthy may naturally rate their health better than that of their ill counterparts, though this link has been observed even in studies which have controlled for socioeconomic status, psychological functioning and health status.[21] This finding is generally stronger for men than women,[20] though the pattern between genders is not universal across all studies, and some results suggest sex-based differences only appear in certain age groups, for certain causes of mortality and within a specific sub-set of self-ratings of health.[21]
## Retirement
Retirement, a common transition faced by the elderly, may have both positive and negative consequences.[22]
# Societal Impact
Societal aging refers to the demographic aging of populations and societies.[23] Cultural differences in attitudes to aging have been studied.
## Emotional Improvement
Given the physical and cognitive declines seen in aging, a surprising finding is that emotional experience improves with age. Older adults are better at regulating their emotions and experience negative affect less frequently than younger adults and show a positivity effect in their attention and memory. The emotional improvements show up in longitudinal studies as well as in cross-sectional studies, and so cannot be entirely due to only the happier individuals surviving.
# Terminology
The concept of successful aging can be traced back to the 1950s, and popularised in the 1980s. Previous research into aging exaggerated the extent to which health disabilities, such as diabetes or osteoporosis, could be attributed exclusively to age, and research in gerontology exaggerated the homogeneity of samples of elderly people.[24][25]
Successful aging consists of three components:[26]
- Low probability of disease or disability;
- High cognitive and physical function capacity;
- Active engagement with life.
A greater number of people self-report successful aging than those that strictly meet these criteria.[24]
Successful aging may be viewed an interdisciplinary concept, spanning both psychology and sociology, where it is seen as the transaction between society and individuals across the life span with specific focus on the later years of life.[27] The terms "healthy aging"[24] "optimal aging" have been proposed as alternatives to successful aging.
Six suggested dimensions of successful aging include:[11]
- No physical disability over the age of 75 as rated by a physician;
- Good subjective health assessment (i.e. good self-ratings of one's health);
- Length of undisabled life;
- Good mental health;
- Objective social support;
- Self-rated life satisfaction in eight domains, namely marriage, income-related work, children, friendship and social contacts, hobbies, community service activities, religion and recreation/sports
# Theories
## Non-biological Theories
- Selectivity Theory - mediates between Activity and Disengagement Theory, which suggests that it may benefit older people to become more active in some aspects of their lives, more disengaged in others.[28]
## Biological Theories
# Measure of Age
The normal point of time from where to measure the age of a human being is from birth. Age in prenatal development is normally measured in gestational age, taking the last menstruation of the woman as a point of beginning. Alternatively,fertilization age, beginning from fertilization can be taken.
Age is often rounded downward to an integer, where the time of birth is taken to have been 0:00 (in other words, the number of days is first rounded upward, before rounding downward to whole years). Thus the age range 4-11 is until the 12th birthday.
# Related Chapters
- Aging brain
- Biodemography
- Biological immortality
- Calorie restriction
- Gerontology
- Life expectancy
- List of life extension-related topics
- Longevity
- Maturity (psychological)
- Memory and aging
- Michael Ristow
- Mitohormesis
- Population aging
- Retirement
- Senescence
- The Grim Reaper Gene
- Youth bulge | https://www.wikidoc.org/index.php/Age | |
34c1e539532622536a62bf5c330da662d35b0bf5 | wikidoc | Ainhum | Ainhum
# Overview
Ainhum is a painful constriction of the base of the fifth toe frequently followed by bilateral spontaneous amputation (autoamputation) a few years later. The disease occurs predominantly in black Africans and their descendants, and occurs worldwide e.g. as a consequence of palmoplantar keratoderma. The exact etiology is still unclear.
# History
Ainhum was first reported as a distinct disease and described in detail by J. F. da Silva Lima in 1867. He recognised a disease of the fifth toe suffered by the Nagos tribe of Bahia, Brazil. This disease was called “ainhum” by the Nagos and means “to saw”, characterising the painful loss of the fifth toe. The origin of these term was thought to be African. Due to slave trade, the Nagos were related to a native tribe in Nigeria.
# Epidemiology
Ainhum predominantly affects black people, living in West Africa, South America and India. In Nigeria it is a common disease with an incidence of 2.2%. Daccarett recorded retrospectively a rate of 1.7% in a mainly African American population in Chicago. Up to now only a few cases had been reported in Europe. Ainhum usually affects people between 20 and 50 years. The average age is about thirty-eight. The youngest recorded patient was seven years old. There is no predominant gender ratio.
# Etiology and Pathogenesis
The true cause of ainhum remains unclear. It is not due to infection by parasites, fungi, bacteria or virus, and it is not related to injury. Walking barefoot in childhood had been linked to this disease, but ainhum also occurs in patients who have never gone barefoot. Race seems to be one of the most predisposing factors and it may has a genetic component, since it has been reported to occur within families. Dent et al. discussed a genetically caused abnormality of the blood supply to the foot. Peripheral limb angiography in five limbs with ainhum showed that the posterior tibial artery became attenuated at the ankle, and the plantar arch and its branches were absent. The dorsal pedis artery was constituting the only supply to the forefoot and little toe.
# Clinical Findings
The groove begins on the lower and internal side of the base of the fifth toe, usually according to the plantar-digital fold. The groove becomes gradually deeper and more circular. The rate of spread is variable, and the disease may progress to a full circle in a few months, or still be incomplete after years. In about 75 per cent both feet are affected, though not usually to the same degree. There is no case reported where it begins in any other toe than the fifth, while there is occasionally a groove on the fourth or third toe. The distal part of the toe swells and appears like a small “potato”. The swelling is due to lymphatic edema distal to the constriction. After a time crusts can appear in the groove which can be infected with staphylococcus.
While the groove becomes deeper, compression of tendons, vessels and nerves occurs. Bone is absorbed by pressure, without any evidence of infection. After a certain time all structures distal the stricture are reduced to an avascular cord. The toe’s connection to the foot becomes increasingly slender, and if it is not amputated, it spontaneously drops off without any bleeding. Normally it takes about five years for an autoamputation to occur. Cole describes four stages of ainhum:
- Grade I: groove
- Grade II: floor of the groove is ulcerated
- Grade III: bone involvement
- Grade IV: autoamputation has occurred
# Symptoms
Pain is present in about 78% of cases. Slight pain is present in the earliest stage of ainhum, caused by pressure on the underlying nerves. Fracture of the phalanx or chronic sepsis is accompanied with severe pain.
# Histology
Histology shows a change in the prickle cell layer, and this is responsible for the laying down of condensed keratin causing the groove. The junctional tissue is reduced to a slender fibrous thread, almost avascular, and all the tissues beyond the constricting band is repressed by a fibro-fatty mass covered by hyperkeratotic integument.
# Imaging
Soft tissue constriction on the medial aspect of the fifth toe is the most frequently presented radiological sign in the early stages. Distal swelling of the toe is considered to be a feature of the disease. In grade III lesions osteolysis is seen in the region of the proximal interphalangeal joint with a characteristic tapering effect. Dispersal of the head of the proximal phalanx is frequently seen. Finally, after autoamputation, the base of the proximal phalanx remains. Radiological examination allows early diagnosis and staging of ainhum. Early diagnosis is crucial to prevent amputation.
# Differential Diagnosis
Ainhum is an acquired and progressive condition, and thus differs from congenital annular constrictions. Ainhum has been much confused with other diseases such as leprosy, diabetic gangrene, syringomyelia, scleroderma or Vohwinkel syndrome.
# Treatment
Incisions across the groove turned out to be ineffective. Excision of the groove followed by z-plasty could relieve pain and prevent autoamputation in Grade I and Grade II lesions. Grade III lesions are treated with disarticulating the metatarsophalangeal joint. This also relieves pain, and all patients have a useful and stable foot. | Ainhum
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Ainhum is a painful constriction of the base of the fifth toe frequently followed by bilateral spontaneous amputation (autoamputation) a few years later. The disease occurs predominantly in black Africans and their descendants, and occurs worldwide e.g. as a consequence of palmoplantar keratoderma. The exact etiology is still unclear.
# History
Ainhum was first reported as a distinct disease and described in detail by J. F. da Silva Lima in 1867. He recognised a disease of the fifth toe suffered by the Nagos tribe of Bahia, Brazil. This disease was called “ainhum” by the Nagos and means “to saw”, characterising the painful loss of the fifth toe. The origin of these term was thought to be African. Due to slave trade, the Nagos were related to a native tribe in Nigeria.
# Epidemiology
Ainhum predominantly affects black people, living in West Africa, South America and India. In Nigeria it is a common disease with an incidence of 2.2%. Daccarett recorded retrospectively a rate of 1.7% in a mainly African American population in Chicago. Up to now only a few cases had been reported in Europe. Ainhum usually affects people between 20 and 50 years. The average age is about thirty-eight. The youngest recorded patient was seven years old. There is no predominant gender ratio.
# Etiology and Pathogenesis
The true cause of ainhum remains unclear. It is not due to infection by parasites, fungi, bacteria or virus, and it is not related to injury. Walking barefoot in childhood had been linked to this disease, but ainhum also occurs in patients who have never gone barefoot. Race seems to be one of the most predisposing factors and it may has a genetic component, since it has been reported to occur within families. Dent et al. discussed a genetically caused abnormality of the blood supply to the foot. Peripheral limb angiography in five limbs with ainhum showed that the posterior tibial artery became attenuated at the ankle, and the plantar arch and its branches were absent. The dorsal pedis artery was constituting the only supply to the forefoot and little toe.
# Clinical Findings
The groove begins on the lower and internal side of the base of the fifth toe, usually according to the plantar-digital fold. The groove becomes gradually deeper and more circular. The rate of spread is variable, and the disease may progress to a full circle in a few months, or still be incomplete after years. In about 75 per cent both feet are affected, though not usually to the same degree. There is no case reported where it begins in any other toe than the fifth, while there is occasionally a groove on the fourth or third toe. The distal part of the toe swells and appears like a small “potato”. The swelling is due to lymphatic edema distal to the constriction. After a time crusts can appear in the groove which can be infected with staphylococcus.
While the groove becomes deeper, compression of tendons, vessels and nerves occurs. Bone is absorbed by pressure, without any evidence of infection. After a certain time all structures distal the stricture are reduced to an avascular cord. The toe’s connection to the foot becomes increasingly slender, and if it is not amputated, it spontaneously drops off without any bleeding. Normally it takes about five years for an autoamputation to occur. Cole describes four stages of ainhum:
• Grade I: groove
• Grade II: floor of the groove is ulcerated
• Grade III: bone involvement
• Grade IV: autoamputation has occurred
# Symptoms
Pain is present in about 78% of cases. Slight pain is present in the earliest stage of ainhum, caused by pressure on the underlying nerves. Fracture of the phalanx or chronic sepsis is accompanied with severe pain.
# Histology
Histology shows a change in the prickle cell layer, and this is responsible for the laying down of condensed keratin causing the groove. The junctional tissue is reduced to a slender fibrous thread, almost avascular, and all the tissues beyond the constricting band is repressed by a fibro-fatty mass covered by hyperkeratotic integument.
# Imaging
Soft tissue constriction on the medial aspect of the fifth toe is the most frequently presented radiological sign in the early stages. Distal swelling of the toe is considered to be a feature of the disease. In grade III lesions osteolysis is seen in the region of the proximal interphalangeal joint with a characteristic tapering effect. Dispersal of the head of the proximal phalanx is frequently seen. Finally, after autoamputation, the base of the proximal phalanx remains. Radiological examination allows early diagnosis and staging of ainhum. Early diagnosis is crucial to prevent amputation.
# Differential Diagnosis
Ainhum is an acquired and progressive condition, and thus differs from congenital annular constrictions. Ainhum has been much confused with other diseases such as leprosy, diabetic gangrene, syringomyelia, scleroderma or Vohwinkel syndrome.
# Treatment
Incisions across the groove turned out to be ineffective. Excision of the groove followed by z-plasty could relieve pain and prevent autoamputation in Grade I and Grade II lesions. Grade III lesions are treated with disarticulating the metatarsophalangeal joint. This also relieves pain, and all patients have a useful and stable foot.
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Ainhum | |
796049b561c1514ba1dabd7adfa29574c5fde5cf | wikidoc | Airway | Airway
# Overview
The airways are those parts of the respiratory system through which air flows, to get from the external environment to the alveoli.
The airway begins at the mouth or nose, and accesses the trachea via the pharynx. The trachea branches into the left and right main bronchi at the carina, situated at the level of the second thoracic vertebra. The bronchi branch into large bronchioles, one for each lobe of the lung. Within the lobes, the bronchi further subdivide some 20 times, ending in clusters of alveoli.
The epithelial surfaces of the airways contain cilia. Inhaled particles stick to mucus (secreted by goblet cells) which is continuously removed from the airways by these cilia. The airway epithelium also secretes a watery fluid upon which the mucus can ride freely. The production of this fluid is impaired by the disease cystic fibrosis. Macrophages are present in the airways. These cells protect the airways from infection by engulfing inhaled particles and bacteria.
Certain conditions require tracheal intubation to secure the airway. Airway devices are used to assist intubation. | Airway
Editor in Chief: Liudvikas Jagminas, M.D., FACEP [1] Phone: 401-729-2419
Template:Otheruses1
# Overview
The airways are those parts of the respiratory system through which air flows, to get from the external environment to the alveoli.
The airway begins at the mouth or nose, and accesses the trachea via the pharynx. The trachea branches into the left and right main bronchi at the carina, situated at the level of the second thoracic vertebra. The bronchi branch into large bronchioles, one for each lobe of the lung. Within the lobes, the bronchi further subdivide some 20 times, ending in clusters of alveoli.
The epithelial surfaces of the airways contain cilia. Inhaled particles stick to mucus (secreted by goblet cells) which is continuously removed from the airways by these cilia. The airway epithelium also secretes a watery fluid upon which the mucus can ride freely. The production of this fluid is impaired by the disease cystic fibrosis. Macrophages are present in the airways. These cells protect the airways from infection by engulfing inhaled particles and bacteria.
Certain conditions require tracheal intubation to secure the airway. Airway devices are used to assist intubation.
# External links
- The Virtual Airway Device, a free resource about airway devices, including a video library
de:Atemwege
fi:Hengitystiet
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Airway | |
0596e318f920600dd0c5d50d603c90c550365a37 | wikidoc | Ajwain | Ajwain
Ajwain (also known as carom seeds or bishop's weed), is an uncommon spice except in certain areas of Asia. It is the small seed-like fruit of the Bishop's Weed plant, (Trachyspermum ammi syn. Carum copticum), egg-shaped and grayish in colour. The plant has a similarity to parsley. Because of their seed-like appearance, the fruit pods are sometimes called ajwain seeds or bishop's weed seeds.
Ajwain is often confused with lovage seed; even some dictionaries mistakenly state that ajwain comes from the lovage plant.
Ajwain is also called 'owa' in Marathi, 'vaamu' in Telugu, "omam" (ஓமம்) in Tamil, "ajwana" in Kannada, "ajmo" in Gujarati, "jowan" in Bengali and "asamodagam" in Singhalese.
# Flavour and aroma
Raw ajwain smells almost exactly like thyme because it also contains thymol, but is more aromatic and less subtle in taste, as well as slightly bitter and pungent. It tastes like thyme or caraway, only stronger. Even a small amount of raw ajwain will completely dominate the flavor of a dish.
In Indian cuisine, ajwain is almost never used raw, but either dry-roasted or fried in ghee or oil. This develops a much more subtle and complex aroma, somewhat similar to caraway but "brighter". Among other things, it is used for making a type of paratha, called 'ajwain ka paratha'.
# History
Ajwain originated in the Middle East, possibly in Egypt. It is now primarily grown and used in the Indian Subcontinent, but also in Iran, Egypt and Afghanistan. It is sometimes used as an ingredient in berbere, a spice mixture favored in Eritrea and Ethiopia.
# Uses
It reduces flatulence caused by beans when it is cooked with beans. It may be used as a substitute for cumin as well. It is also traditionally known as a digestive aid and an antiemetic. | Ajwain
Ajwain (also known as carom seeds or bishop's weed), is an uncommon spice except in certain areas of Asia. It is the small seed-like fruit of the Bishop's Weed plant, (Trachyspermum ammi syn. Carum copticum), egg-shaped and grayish in colour. The plant has a similarity to parsley. Because of their seed-like appearance, the fruit pods are sometimes called ajwain seeds or bishop's weed seeds.
Ajwain is often confused with lovage seed; even some dictionaries mistakenly state that ajwain comes from the lovage plant.
Ajwain is also called 'owa' in Marathi, 'vaamu' in Telugu, "omam" (ஓமம்) in Tamil, "ajwana" in Kannada, "ajmo" in Gujarati, "jowan" in Bengali and "asamodagam" in Singhalese.
# Flavour and aroma
Raw ajwain smells almost exactly like thyme because it also contains thymol, but is more aromatic and less subtle in taste, as well as slightly bitter and pungent. It tastes like thyme or caraway, only stronger. Even a small amount of raw ajwain will completely dominate the flavor of a dish.
In Indian cuisine, ajwain is almost never used raw, but either dry-roasted or fried in ghee or oil. This develops a much more subtle and complex aroma, somewhat similar to caraway but "brighter". Among other things, it is used for making a type of paratha, called 'ajwain ka paratha'.
# History
Ajwain originated in the Middle East, possibly in Egypt. It is now primarily grown and used in the Indian Subcontinent, but also in Iran, Egypt and Afghanistan. It is sometimes used as an ingredient in berbere, a spice mixture favored in Eritrea and Ethiopia.
# Uses
It reduces flatulence caused by beans when it is cooked with beans. It may be used as a substitute for cumin as well. It is also traditionally known as a digestive aid and an antiemetic.
# External links
- Ajwain page from Gernot Katzer's Spice Pages
- New Directions Nacional Ajowan Essential Oil
## Recipes
- Ajwain-Murgh
- Ajwain-flavored chicken
- Palda
- Fried Bhindi
- Papdi
- Jalebi Paratha
- Amritsari Fish
Template:Herbs & spices
de:Ajowan
dv:ހިތި ދަމުއި
it:Carum ajowan
ml:അയമോദകം
nl:Ajowan
fi:Intiankumina
uk:Ажгон
ur:اجوائن | https://www.wikidoc.org/index.php/Ajwain | |
db204e147846f8de274cd5ad389b36841c69ef4b | wikidoc | Albedo | Albedo
The albedo of an object is the extent to which it diffusely reflects light from the sun. It is therefore a more specific form of the term reflectivity. Albedo is defined as
the ratio of diffusely reflected to incident electromagnetic radiation. It is a unitless measure indicative of a surface's or body's diffuse reflectivity. The word is derived from Latin albedo "whiteness", in turn from albus "white". The range of possible values is from 0 (dark) to 1 (bright).
The albedo is an important concept in climatology and astronomy. In climatology it is sometimes expressed as a percentage. Its value depends on the frequency of radiation considered: unqualified, it usually refers to some appropriate average across the spectrum of visible light. In general, the albedo depends on the direction and directional distribution of incoming radiation. Exceptions are Lambertian surfaces, which scatter radiation in all directions in a cosine function, so their albedo does not depend on the incoming distribution. In realistic cases, a bidirectional reflectance distribution function (BRDF) is required to characterize the scattering properties of a surface accurately, although albedos are a very useful first approximation.
# Terrestrial albedo
Albedos of typical materials in visible light range from up to 90% for fresh snow, to about 4% for charcoal, one of the darkest substances. Deeply shadowed cavities can achieve an effective albedo approaching the zero of a blackbody. When seen from a distance, the ocean surface has a low albedo, as do most forests, while desert areas have some of the highest albedos among landforms. Most land areas are in an albedo range of .1 to .4. The average albedo of the Earth is about 30%. This is far higher than for the ocean primarily because of the contribution of clouds.
Human activities have changed the albedo (via forest clearance and farming, for example) of various areas around the globe. However, quantification of this effect is difficult on the global scale.
The classic example of albedo effect is the snow-temperature feedback. If a snow covered area warms and the snow melts, the albedo decreases, more sunlight is absorbed, and the temperature tends to increase. The converse is true: if snow forms, a cooling cycle happens. The intensity of the albedo effect depends on the size of the change in albedo and the amount of insolation; for this reason it can be potentially very large in the tropics.
The Earth's surface albedo is regularly estimated via Earth observation satellite sensors such as NASA's MODIS instruments onboard the Terra and Aqua satellites. As the total amount of reflected radiation cannot be directly measured by satellite, a mathematical model of the BRDF is used to translate a sample set of satellite reflectance measurements into estimates of directional-hemispherical reflectance and bi-hemispherical reflectance.
## White-sky and black-sky albedo
It has been shown that for many applications involving terrestrial albedo, the albedo at a particular solar zenith angle {\theta_i} can reasonably be approximated by the proportionate sum of two terms: the directional-hemispherical reflectance at that solar zenith angle, {\bar \alpha(\theta_i)}, and the bi-hemispherical reflectance, {\bar \bar \alpha} the proportion concerned being defined as the proportion of diffuse illumination {D}.
Albedo {\alpha} can then be given as:
{\alpha}= (1-D) \bar \alpha(\theta_i) + D \bar \bar \alpha.
Directional-hemispherical reflectance is sometimes referred to as black-sky albedo and bi-hemispherical reflectance as white sky albedo. These terms are important because they allow the albedo to be calculated for any given illumination conditions from a knowledge of the intrinsic properties of the surface.
# Astronomical albedo
The albedo of planets, satellites and asteroids can be used to infer much about their properties. The study of albedos, their dependence on wavelength, lighting angle ("phase angle"), and variation in time comprises a major part of the astronomical field of photometry. For small and far objects that cannot be resolved by telescopes, much of what we know comes from the study of their albedos. For example, the absolute albedo can indicate the surface ice content of outer solar system objects, the variation of albedo with phase angle gives information about regolith properties, while unusually high radar albedo is indicative of high metallic content in asteroids.
Enceladus, a moon of Saturn, has one of the highest known albedos of any body in the solar system, with 99% of EM radiation reflected. Another notable high albedo body is Eris, with an albedo of 86%. Many objects in the outer solar system and asteroid belt have low albedos down to about 5%. Such a dark surface is thought to be indicative of a primitive and heavily space weathered surface containing some organic compounds.
The overall albedo of the Moon is around 7%, but it is strongly directional and non-Lambertian, displaying also a strong opposition effect. While such reflectance properties are different from those of any terrestrial terrains, they are typical of the regolith surfaces of airless solar system bodies.
Two common albedos that are used in astronomy are the geometric albedo (measuring brightness when illumination comes from directly behind the observer) and the Bond albedo (measuring total proportion of electromagnetic energy reflected). Their values can differ significantly, which is a common source of confusion.
In detailed studies, the directional reflectance properties of astronomical bodies are often expressed in terms of the five Hapke parameters which semi-empirically describe the variation of albedo with phase angle, including a characterization of the opposition effect of regolith surfaces.
The correlation between astronomical (geometric) albedo, absolute magnitude and diameter is
A =\left ( \frac{1329\times10^{-H/5}}{D} \right ) ^2,
where A is astronomical albedo, D is diameter in km, and H is the absolute magnitude.
# Other types of albedo
Single scattering albedo - is used to define scattering of electromagnetic waves on small particles. It depends on properties of the material (refractive index), the size of the particle(s), and the wavelength of the incoming radiation.
# Some examples of terrestrial albedo effects
## Fairbanks, Alaska
According to the National Climatic Data Center's GHCN 2 data, which is composed of 30-year smoothed climatic means for thousands of weather stations across the world, the college weather station at Fairbanks, Alaska, is about 3 °C (5.4 °F) warmer than the airport at Fairbanks, partly because of air drainage patterns but also largely because of the lower albedo at the college resulting from a higher concentration of spruce trees and therefore less open snowy ground to reflect the heat back into space.
## The tropics
Although the albedo-temperature effect is most famous in colder regions of Earth, because more snow falls there, it is actually much stronger in tropical regions because in the tropics there is consistently more sunlight. When Brazilian ranchers cut down dark, tropical rainforest trees to replace them with even darker soil in order to grow crops, the average temperature of the area increases up to 3 °C (5.4 °F) year-round, although part of the effect is due to changed evaporation (latent heat flux).
## Small scale effects
Albedo works on a smaller scale, too. People who wear dark clothes in the summertime put themselves at a greater risk of heatstroke than those who wear lighter color clothes.
## Albedo of various terrains
The albedo of a pine forest at 45°N in the winter in which the trees cover the land surface completely is only about 9%, among the lowest of any naturally occurring land environment. This is partly due to the color of the pines, and partly due to multiple scattering of sunlight within the trees which lowers the overall reflected light level. Due to light penetration, the ocean's albedo is even lower at about 3.5%, though this depends strongly on the angle of the incident radiation. Dense swampland averages between 9% and 14%. Deciduous trees average about 13%. A grassy field usually comes in at about 20%. A barren field will depend on the color of the soil, and can be as low as 5% or as high as 40%, with 15% being about the average for farmland. A desert or large beach usually averages around 25% but varies depending on the color of the sand.
## Urban areas
Urban areas in particular have very unnatural values for albedo because of the many human-built structures which absorb light before the light can reach the surface. In the northern part of the world, cities are relatively dark, and Walker has shown that their average albedo is about 7%, with only a slight increase during the summer. In most tropical countries, cities average around 12%. This is similar to the values found in northern suburban transitional zones. Part of the reason for this is the different natural environment of cities in tropical regions, e.g., there are more very dark trees around; another reason is that portions of the tropics are very poor, and city buildings must be built with different materials. Warmer regions may also choose lighter colored building materials so the structures will remain cooler.
## Trees
Because trees tend to have a low albedo, removing forests would tend to increase albedo and thereby could produce localized climate cooling. Cloud feedbacks further complicate the issue. In seasonally snow-covered zones, winter albedos of treeless areas are 10% to 50% higher than nearby forested areas because snow does not cover the trees as readily. Deciduous trees have an albedo value of about 0.15 to 0.18 while coniferous trees have a value of about 0.09 to 0.15. The difference between deciduous and coniferous is because coniferous trees are darker in general and have cone-shape seeds. The pattern of these seeds trap light energy more than deciduous trees.
Studies by the Hadley Centre have investigated the relative (generally warming) effect of albedo change and (cooling) effect of carbon sequestration on planting forests. They found that new forests in tropical and midlatitude areas tended to cool; new forests in high latitudes (e.g. Siberia) were neutral or perhaps warming.
## Snow
Snow albedos can be as high as 90%; this, however, is for the ideal example: fresh deep snow over a featureless landscape. Over Antarctica they average a little more than 80%.
If a marginally snow-covered area warms, snow tends to melt, lowering the albedo, and hence leading to more snowmelt (the ice-albedo positive feedback). This is the basis for predictions of enhanced warming in the polar and seasonally snow covered regions as a result of global warming.
## Water
Water reflects light very differently from typical terrestrial materials. The reflectivity of a water surface is calculated using the Fresnel equations (see graph).
At the scale of the wavelength of light even wavy water is always smooth so the light is reflected in a specular manner (not diffusely). The glint of light off water is a commonplace effect of this. At small angles of incident light, waviness results in reduced reflectivity (from as high as 100%) because of the steepness of the reflectivity-vs.-incident-angle curve and a locally increased average incident angle.
Although the reflectivity of water is very low at high and medium angles of incident light, it increases tremendously at small angles of incident light such as occur on the illuminated side of the earth near the terminator (early morning, late afternoon and near the poles). However, as mentioned above, waviness causes an appreciable reduction. Since the light specularly reflected from water does not usually reach the viewer, water is usually considered to have a very low albedo in spite of its high reflectivity at low angles of incident light.
Note that white caps on waves look white (and have high albedo) because the water is foamed up (not smooth at the scale of the wavelength of light) so the Fresnel equations do not apply. Fresh ‘black’ ice exhibits Fresnel reflection.
## Clouds
Clouds are another source of albedo that play into the global warming equation. Different types of clouds have different albedo values, theoretically ranging from a minimum of near 0% to a maximum in the high 70s. "On any given day, about half of Earth is covered by clouds, which reflect more sunlight than land and water. Clouds keep Earth cool by reflecting sunlight, but they can also serve as blankets to trap warmth."
Albedo and climate in some areas are already affected by artificial clouds, such as those created by the contrails of heavy commercial airliner traffic. A study following the burning of the Kuwaiti oil fields by Saddam Hussein showed that temperatures under the burning oil fires were as much as 10oC colder than temperatures several miles away under clear skies.
## Aerosol effects
Aerosol (very fine particles/droplets in the atmosphere) has two effects, direct and indirect. The direct (albedo) effect is generally to cool the planet; the indirect effect (the particles act as CCNs and thereby change cloud properties) is less certain.
## Black carbon
Another albedo-related effect on the climate is from black carbon particles. The size of this effect is difficult to quantify: the IPCC say that their "estimate of the global mean radiative forcing for BC aerosols from fossil fuels is ... +0.2 W m-2 (from +0.1 W m-2 in the SAR) with a range +0.1 to +0.4 W m...-2". | Albedo
The albedo of an object is the extent to which it diffusely reflects light from the sun. It is therefore a more specific form of the term reflectivity. Albedo is defined as
the ratio of diffusely reflected to incident electromagnetic radiation. It is a unitless measure indicative of a surface's or body's diffuse reflectivity. The word is derived from Latin albedo "whiteness", in turn from albus "white". The range of possible values is from 0 (dark) to 1 (bright).
The albedo is an important concept in climatology and astronomy. In climatology it is sometimes expressed as a percentage. Its value depends on the frequency of radiation considered: unqualified, it usually refers to some appropriate average across the spectrum of visible light. In general, the albedo depends on the direction and directional distribution of incoming radiation. Exceptions are Lambertian surfaces, which scatter radiation in all directions in a cosine function, so their albedo does not depend on the incoming distribution. In realistic cases, a bidirectional reflectance distribution function (BRDF) is required to characterize the scattering properties of a surface accurately, although albedos are a very useful first approximation.
# Terrestrial albedo
Albedos of typical materials in visible light range from up to 90% for fresh snow, to about 4% for charcoal, one of the darkest substances. Deeply shadowed cavities can achieve an effective albedo approaching the zero of a blackbody. When seen from a distance, the ocean surface has a low albedo, as do most forests, while desert areas have some of the highest albedos among landforms. Most land areas are in an albedo range of .1 to .4.[5] The average albedo of the Earth is about 30%.[6] This is far higher than for the ocean primarily because of the contribution of clouds.
Human activities have changed the albedo (via forest clearance and farming, for example) of various areas around the globe. However, quantification of this effect is difficult on the global scale.
The classic example of albedo effect is the snow-temperature feedback. If a snow covered area warms and the snow melts, the albedo decreases, more sunlight is absorbed, and the temperature tends to increase. The converse is true: if snow forms, a cooling cycle happens. The intensity of the albedo effect depends on the size of the change in albedo and the amount of insolation; for this reason it can be potentially very large in the tropics.
The Earth's surface albedo is regularly estimated via Earth observation satellite sensors such as NASA's MODIS instruments onboard the Terra and Aqua satellites. As the total amount of reflected radiation cannot be directly measured by satellite, a mathematical model of the BRDF is used to translate a sample set of satellite reflectance measurements into estimates of directional-hemispherical reflectance and bi-hemispherical reflectance.
## White-sky and black-sky albedo
It has been shown that for many applications involving terrestrial albedo, the albedo at a particular solar zenith angle <math>{\theta_i}</math> can reasonably be approximated by the proportionate sum of two terms: the directional-hemispherical reflectance at that solar zenith angle, <math>{\bar \alpha(\theta_i)}</math>, and the bi-hemispherical reflectance, <math>{\bar \bar \alpha}</math> the proportion concerned being defined as the proportion of diffuse illumination <math>{D}</math>.
Albedo <math>{\alpha}</math> can then be given as:
<math>{\alpha}= (1-D) \bar \alpha(\theta_i) + D \bar \bar \alpha.</math>
Directional-hemispherical reflectance is sometimes referred to as black-sky albedo and bi-hemispherical reflectance as white sky albedo. These terms are important because they allow the albedo to be calculated for any given illumination conditions from a knowledge of the intrinsic properties of the surface.
# Astronomical albedo
The albedo of planets, satellites and asteroids can be used to infer much about their properties. The study of albedos, their dependence on wavelength, lighting angle ("phase angle"), and variation in time comprises a major part of the astronomical field of photometry. For small and far objects that cannot be resolved by telescopes, much of what we know comes from the study of their albedos. For example, the absolute albedo can indicate the surface ice content of outer solar system objects, the variation of albedo with phase angle gives information about regolith properties, while unusually high radar albedo is indicative of high metallic content in asteroids.
Enceladus, a moon of Saturn, has one of the highest known albedos of any body in the solar system, with 99% of EM radiation reflected. Another notable high albedo body is Eris, with an albedo of 86%. Many objects in the outer solar system and asteroid belt have low albedos down to about 5%. Such a dark surface is thought to be indicative of a primitive and heavily space weathered surface containing some organic compounds.
The overall albedo of the Moon is around 7%, but it is strongly directional and non-Lambertian, displaying also a strong opposition effect.[7] While such reflectance properties are different from those of any terrestrial terrains, they are typical of the regolith surfaces of airless solar system bodies.
Two common albedos that are used in astronomy are the geometric albedo (measuring brightness when illumination comes from directly behind the observer) and the Bond albedo (measuring total proportion of electromagnetic energy reflected). Their values can differ significantly, which is a common source of confusion.
In detailed studies, the directional reflectance properties of astronomical bodies are often expressed in terms of the five Hapke parameters which semi-empirically describe the variation of albedo with phase angle, including a characterization of the opposition effect of regolith surfaces.
The correlation between astronomical (geometric) albedo, absolute magnitude and diameter is
<math>A =\left ( \frac{1329\times10^{-H/5}}{D} \right ) ^2</math>,
where <math>A</math> is astronomical albedo, <math>D</math> is diameter in km, and H is the absolute magnitude.
# Other types of albedo
Single scattering albedo - is used to define scattering of electromagnetic waves on small particles. It depends on properties of the material (refractive index), the size of the particle(s), and the wavelength of the incoming radiation.
# Some examples of terrestrial albedo effects
## Fairbanks, Alaska
According to the National Climatic Data Center's GHCN 2 data, which is composed of 30-year smoothed climatic means for thousands of weather stations across the world, the college weather station at Fairbanks, Alaska, is about 3 °C (5.4 °F) warmer than the airport at Fairbanks, partly because of air drainage patterns but also largely because of the lower albedo at the college resulting from a higher concentration of spruce trees and therefore less open snowy ground to reflect the heat back into space.
## The tropics
Although the albedo-temperature effect is most famous in colder regions of Earth, because more snow falls there, it is actually much stronger in tropical regions because in the tropics there is consistently more sunlight. When Brazilian ranchers cut down dark, tropical rainforest trees to replace them with even darker soil in order to grow crops, the average temperature of the area increases up to 3 °C (5.4 °F) year-round,[8][9] although part of the effect is due to changed evaporation (latent heat flux).
## Small scale effects
Albedo works on a smaller scale, too. People who wear dark clothes in the summertime put themselves at a greater risk of heatstroke than those who wear lighter color clothes.[10]
## Albedo of various terrains
The albedo of a pine forest at 45°N in the winter in which the trees cover the land surface completely is only about 9%, among the lowest of any naturally occurring land environment. This is partly due to the color of the pines, and partly due to multiple scattering of sunlight within the trees which lowers the overall reflected light level. Due to light penetration, the ocean's albedo is even lower at about 3.5%, though this depends strongly on the angle of the incident radiation. Dense swampland averages between 9% and 14%. Deciduous trees average about 13%. A grassy field usually comes in at about 20%. A barren field will depend on the color of the soil, and can be as low as 5% or as high as 40%, with 15% being about the average for farmland. A desert or large beach usually averages around 25% but varies depending on the color of the sand.
## Urban areas
Urban areas in particular have very unnatural values for albedo because of the many human-built structures which absorb light before the light can reach the surface. In the northern part of the world, cities are relatively dark, and Walker has shown that their average albedo is about 7%, with only a slight increase during the summer. In most tropical countries, cities average around 12%. This is similar to the values found in northern suburban transitional zones. Part of the reason for this is the different natural environment of cities in tropical regions, e.g., there are more very dark trees around; another reason is that portions of the tropics are very poor, and city buildings must be built with different materials. Warmer regions may also choose lighter colored building materials so the structures will remain cooler.
## Trees
Because trees tend to have a low albedo, removing forests would tend to increase albedo and thereby could produce localized climate cooling. Cloud feedbacks further complicate the issue. In seasonally snow-covered zones, winter albedos of treeless areas are 10% to 50% higher than nearby forested areas because snow does not cover the trees as readily. Deciduous trees have an albedo value of about 0.15 to 0.18 while coniferous trees have a value of about 0.09 to 0.15.[11] The difference between deciduous and coniferous is because coniferous trees are darker in general and have cone-shape seeds. The pattern of these seeds trap light energy more than deciduous trees.
Studies by the Hadley Centre have investigated the relative (generally warming) effect of albedo change and (cooling) effect of carbon sequestration on planting forests. They found that new forests in tropical and midlatitude areas tended to cool; new forests in high latitudes (e.g. Siberia) were neutral or perhaps warming.[12]
## Snow
Snow albedos can be as high as 90%; this, however, is for the ideal example: fresh deep snow over a featureless landscape. Over Antarctica they average a little more than 80%.
If a marginally snow-covered area warms, snow tends to melt, lowering the albedo, and hence leading to more snowmelt (the ice-albedo positive feedback). This is the basis for predictions of enhanced warming in the polar and seasonally snow covered regions as a result of global warming.
## Water
Water reflects light very differently from typical terrestrial materials. The reflectivity of a water surface is calculated using the Fresnel equations (see graph).
At the scale of the wavelength of light even wavy water is always smooth so the light is reflected in a specular manner (not diffusely). The glint of light off water is a commonplace effect of this. At small angles of incident light, waviness results in reduced reflectivity (from as high as 100%) because of the steepness of the reflectivity-vs.-incident-angle curve and a locally increased average incident angle.[13]
Although the reflectivity of water is very low at high and medium angles of incident light, it increases tremendously at small angles of incident light such as occur on the illuminated side of the earth near the terminator (early morning, late afternoon and near the poles). However, as mentioned above, waviness causes an appreciable reduction. Since the light specularly reflected from water does not usually reach the viewer, water is usually considered to have a very low albedo in spite of its high reflectivity at low angles of incident light.
Note that white caps on waves look white (and have high albedo) because the water is foamed up (not smooth at the scale of the wavelength of light) so the Fresnel equations do not apply. Fresh ‘black’ ice exhibits Fresnel reflection.
## Clouds
Clouds are another source of albedo that play into the global warming equation. Different types of clouds have different albedo values, theoretically ranging from a minimum of near 0% to a maximum in the high 70s. "On any given day, about half of Earth is covered by clouds, which reflect more sunlight than land and water. Clouds keep Earth cool by reflecting sunlight, but they can also serve as blankets to trap warmth."[14]
Albedo and climate in some areas are already affected by artificial clouds, such as those created by the contrails of heavy commercial airliner traffic.[15] A study following the burning of the Kuwaiti oil fields by Saddam Hussein showed that temperatures under the burning oil fires were as much as 10oC colder than temperatures several miles away under clear skies.[16]
## Aerosol effects
Aerosol (very fine particles/droplets in the atmosphere) has two effects, direct and indirect. The direct (albedo) effect is generally to cool the planet; the indirect effect (the particles act as CCNs and thereby change cloud properties) is less certain.[17]
## Black carbon
Another albedo-related effect on the climate is from black carbon particles. The size of this effect is difficult to quantify: the IPCC say that their "estimate of the global mean radiative forcing for BC aerosols from fossil fuels is ... +0.2 W m-2 (from +0.1 W m-2 in the SAR) with a range +0.1 to +0.4 W m...-2".[18] | https://www.wikidoc.org/index.php/Albedo | |
4bcb6fbd31866798c102e385c3f85cc7b2524065 | wikidoc | Aldose | Aldose
File:D-glyceraldehyde-2D-Fischer.png
An aldose is a monosaccharide (a simple sugar) containing one aldehyde group per molecule and having a chemical formula of the form CnH2nOn, (n>=3).
With only 3 carbon atoms, glyceraldehyde is the simplest of all aldoses.
Aldoses isomerize to ketoses in the Lobry-de Bruyn-van Ekenstein transformation. Aldose differs from ketose in that it has a carbonyl group at the end of the carbon chain whereas the carbonyl group of a ketose is in the middle; this fact allows them to be chemically differentiated through Seliwanoff's test.
# List of aldoses
- Triose: glyceraldehyde
- Tetroses: erythrose, threose
- Pentoses: ribose, arabinose, xylose, lyxose
- Hexoses: allose, altrose, glucose, mannose, gulose, idose, galactose, talose | Aldose
File:D-glyceraldehyde-2D-Fischer.png
An aldose is a monosaccharide (a simple sugar) containing one aldehyde group per molecule and having a chemical formula of the form CnH2nOn, (n>=3).
With only 3 carbon atoms, glyceraldehyde is the simplest of all aldoses.
Aldoses isomerize to ketoses in the Lobry-de Bruyn-van Ekenstein transformation. Aldose differs from ketose in that it has a carbonyl group at the end of the carbon chain whereas the carbonyl group of a ketose is in the middle; this fact allows them to be chemically differentiated through Seliwanoff's test.
# List of aldoses
- Triose: glyceraldehyde
- Tetroses: erythrose, threose
- Pentoses: ribose, arabinose, xylose, lyxose
- Hexoses: allose, altrose, glucose, mannose, gulose, idose, galactose, talose | https://www.wikidoc.org/index.php/Aldose | |
5ef31acae654967de03910385ea459e49075feab | wikidoc | Alkali | Alkali
In chemistry, an alkali (from Arabic: Al-Qalyالقلي, القالي ) is a basic, ionic salt of an alkali metal or alkaline earth metal element. Alkalis are best known for being bases (compounds with pH greater than 7) that dissolve in water. The adjective alkaline is commonly used in English as a synonym for base, especially for soluble bases. This broad use of the term is likely to have come about because alkalis were the first bases known to obey the Arrhenius definition of a base and are still among the more common bases. Since Brønsted-Lowry acid-base theory, the term alkali in chemistry is normally restricted to those salts containing alkali and alkaline earth metal elements.
# Common properties of alkalis
Alkalines are all Arrhenius bases and share many properties with other chemicals in this group (Arrhenius bases form hydroxide ions when dissolved in water). Common properties of alkaline aqueous solutions include:
- Moderately-concentrated solutions (over 10-3 M) have a pH of 10 or greater. This means that they will turn phenolphthalein from colorless to pink.
- Concentrated solutions are caustic (causing chemical burns).
- Alkaline solutions are slippery or soapy to the touch, due to the saponification of the fatty acids on the surface of the skin.
- Alkalis are normally water soluble, although some like barium carbonate are only soluble when reacting with an acidic aqueous solution.
Alkalis are opposite of acids.
# Confusion between base and alkali
The terms "base" and "alkali" are often used interchangeably, since most common bases are alkalis. It is common to speak of "measuring the alkalinity of soil" when what is actually meant is the measurement of the pH (base property). In a similar manner, bases that are not alkalis, such as ammonia, are sometimes erroneously referred to as alkaline.
Note that not all or even most salts formed by alkali metals are alkaline; this designation applies only to those salts that are basic.
While most electropositive metal oxides are basic, only the soluble alkali metal and alkaline earth metal oxides can be correctly called alkalis.
This definition of an alkali as a basic salt of an alkali metal or alkaline earth metal does appear to be the most common, based on dictionary definitions , however conflicting definitions of the term alkali do exist. These include:
- Any base that is water-soluble and . This is more accurately called an Arrhenius base.
- The solution of a base in water .
# Alkali salts
Most basic salts are alkali salts, of which common examples are:
- sodium hydroxide (often called "caustic soda")
- potassium hydroxide (commonly called "caustic potash")
- lye (generic term, for either of the previous two, or even for a mixture)
- calcium carbonate (sometimes called "free lime")
- magnesium hydroxide is an example of an atypical alkali: it is a weak base (cannot be detected by phenolphthalein) and it has low solubility in water
# Alkaline soil
Soil with a pH value higher than 7.3 is normally referred to as alkaline. This soil property can occur naturally, due to the presence of alkali salts. Although some plants do prefer slightly basic soil (including vegetables like cabbage and fodder like buffalograss), most plants prefer a mildly acidic soil (pH between 6.0 and 6.8), and alkaline soils can cause problems.
# Alkali lakes
In alkali lakes (a type of salt lake), evaporation concentrates the naturally-occurring alkali salts, often forming a crust of mildly-basic salt across a large area.
Examples of alkali lakes:
- Redberry Lake, Saskatchewan, Canada.
- Tramping Lake, Saskatchewan, Canada.
- Mono lake, California, United States of America
# Etymology
The word "alkali" is derived from Arabic al qalīy = the calcined ashes, referring to the original source of alkaline substance. Ashes were used in conjunction with animal fat to produce soap, a process known as saponification.
ar:قلوي
de:Alkalien
et:Leelis
eo:Alkalo
no:Alkali
nov:Alkali
simple:Alkali | Alkali
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
In chemistry, an alkali (from Arabic: Al-Qalyالقلي, القالي ) is a basic, ionic salt of an alkali metal or alkaline earth metal element. Alkalis are best known for being bases (compounds with pH greater than 7) that dissolve in water. The adjective alkaline is commonly used in English as a synonym for base, especially for soluble bases. This broad use of the term is likely to have come about because alkalis were the first bases known to obey the Arrhenius definition of a base and are still among the more common bases. Since Brønsted-Lowry acid-base theory, the term alkali in chemistry is normally restricted to those salts containing alkali and alkaline earth metal elements.
# Common properties of alkalis
Alkalines are all Arrhenius bases and share many properties with other chemicals in this group (Arrhenius bases form hydroxide ions when dissolved in water). Common properties of alkaline aqueous solutions include:
- Moderately-concentrated solutions (over 10-3 M) have a pH of 10 or greater. This means that they will turn phenolphthalein from colorless to pink.
- Concentrated solutions are caustic (causing chemical burns).
- Alkaline solutions are slippery or soapy to the touch, due to the saponification of the fatty acids on the surface of the skin.
- Alkalis are normally water soluble, although some like barium carbonate are only soluble when reacting with an acidic aqueous solution.
Alkalis are opposite of acids.
# Confusion between base and alkali
The terms "base" and "alkali" are often used interchangeably, since most common bases are alkalis. It is common to speak of "measuring the alkalinity of soil" when what is actually meant is the measurement of the pH (base property). In a similar manner, bases that are not alkalis, such as ammonia, are sometimes erroneously referred to as alkaline.
Note that not all or even most salts formed by alkali metals are alkaline; this designation applies only to those salts that are basic.
While most electropositive metal oxides are basic, only the soluble alkali metal and alkaline earth metal oxides can be correctly called alkalis.
This definition of an alkali as a basic salt of an alkali metal or alkaline earth metal does appear to be the most common, based on dictionary definitions [2][3], however conflicting definitions of the term alkali do exist. These include:
- Any base that is water-soluble and [4][5]. This is more accurately called an Arrhenius base.
- The solution of a base in water [6].
# Alkali salts
Most basic salts are alkali salts, of which common examples are:
- sodium hydroxide (often called "caustic soda")
- potassium hydroxide (commonly called "caustic potash")
- lye (generic term, for either of the previous two, or even for a mixture)
- calcium carbonate (sometimes called "free lime")
- magnesium hydroxide is an example of an atypical alkali: it is a weak base (cannot be detected by phenolphthalein) and it has low solubility in water
# Alkaline soil
Soil with a pH value higher than 7.3 is normally referred to as alkaline. This soil property can occur naturally, due to the presence of alkali salts. Although some plants do prefer slightly basic soil (including vegetables like cabbage and fodder like buffalograss), most plants prefer a mildly acidic soil (pH between 6.0 and 6.8), and alkaline soils can cause problems.
# Alkali lakes
In alkali lakes (a type of salt lake), evaporation concentrates the naturally-occurring alkali salts, often forming a crust of mildly-basic salt across a large area.
Examples of alkali lakes:
- Redberry Lake, Saskatchewan, Canada.
- Tramping Lake, Saskatchewan, Canada.
- Mono lake, California, United States of America
# Etymology
The word "alkali" is derived from Arabic al qalīy = the calcined ashes, referring to the original source of alkaline substance. Ashes were used in conjunction with animal fat to produce soap, a process known as saponification.
ar:قلوي
de:Alkalien
et:Leelis
eo:Alkalo
no:Alkali
nov:Alkali
simple:Alkali
Template:Jb1
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Alkali | |
f8868d78079f4aae74708a39bfc561ccdaad9666 | wikidoc | Alkane | Alkane
# Overview
Alkanes, also known as Paraffins, are chemical compounds that consist only of the elements carbon (C) and hydrogen (H) (i.e. hydrocarbons), where each of these atoms are linked together exclusively by single bonds (i.e. they are saturated compounds) without any cyclic structure (i.e. loops). Alkanes belong to a homologous series of organic compounds in which the members differ by a constant relative atomic mass of 14.
Each carbon atom must have 4 bonds (either C-H or C-C bonds), and each hydrogen atom must be joined to a carbon atom (H-C bonds). A series of linked carbon atoms is known as the carbon skeleton or carbon backbone. Typically the number of carbon atoms is often used to define the size of the alkane (e.g. C2-alkane).
An alkyl group is a functional group or side chain which, like an alkane, consists solely of singly bonded carbon and hydrogen atoms, for example a methyl or ethyl group.
Saturated hydrocarbons can be linear (general formula CnH2n+2) where the carbon atoms are joined in a snake-like structure, branched (general formula CnH2n+2, n>3) where the carbon backbone splits off in one or more directions, or cyclic (general formula CnH2n, n>2) where the carbon backbone is linked so as to form a loop. According to the definition by IUPAC, the former two are alkanes, while the third group is called cycloalkanes. In other words, saturated hydrocarbons are divided into alkanes and cycloalkanes, depending on whether or not they have cyclic structures, and technically, cycloalkanes are not alkanes. However, cycloalkanes are sometimes called cyclic alkanes, confusingly, when "real" alkanes are called acyclic alkanes. Saturated hydrocarbons can also combine any of the linear, cyclic (e.g. polycyclic) and branching structures, and they are still alkanes (no general formula) as long as they are acyclic (i.e. having no loops).
The simplest possible alkane (the parent molecule) is methane, CH4. There is no limit to the number of carbon atoms that can be linked together, the only limitation being that the molecule is acyclic, is saturated, and is a hydrocarbon. Saturated oils and waxes are examples of larger alkanes where the number of carbons in the carbon backbone tends to be greater than 10.
Alkanes are not very reactive and have little biological activity. Alkanes can be viewed as a molecular scaffold upon which can be hung the interesting biologically active/reactive portions (functional groups) of the molecule.
# Isomerism
Alkanes with more than three carbon atoms can be arranged in a multiple number of ways, forming different structural isomers. An isomer is like a chemical anagram, in which the atoms of a chemical compound are arranged or joined together in a different order. The simplest isomer of an alkane is the one in which the carbon atoms are arranged in a single chain with no branches. This isomer is sometimes called the n-isomer (n for "normal", although it is not necessarily the most common). However the chain of carbon atoms may also be branched at one or more points. The number of possible isomers increases rapidly with the number of carbon atoms. For example:
- C1: 1 isomer — methane
- C2: 1 isomer — ethane
- C3: 1 isomers — propane
- C4: 2 isomers — n-butane, isobutane
- C12: 355 isomers
- C32: 27,711,253,769 isomers
- C60: 22,158,734,535,770,411,074,184 isomers
In addition to these isomers, the chain of carbon atoms may form one or more loops. Such compounds are called cycloalkanes.
# Nomenclature
The IUPAC nomenclature (systematic way of naming compounds) for alkanes is based on identifying hydrocarbon chains. Unbranched, saturated hydrocarbon chains are named systematically with a Greek numerical prefix denoting the number of carbons and the suffix "-ane".
August Wilhelm von Hofmann suggested systematizing nomenclature by using the whole sequence of vowels a, e, i, o and u to create suffixes -ane, -ene, -ine (or -yne), -one, -une, for the hydrocarbons. The first three name hydrocarbons with single, double and triple bonds. "-one" represents a ketone. "-ol" represents an alcohol or OH group. "-oxy-" means an ether and refers to oxygen between two carbons, so that methoxy-methane is the IUPAC name for dimethyl ether.
It is difficult or impossible to find compounds with more than one IUPAC name. This is because shorter chains attached to longer chains are prefixes and the convention includes brackets. Numbers in the name, referring to which carbon a group is attached to, should be as low as possible, so that 1- is implied and usually omitted from names of organic compounds with only one side-group. "1-" is implied in Nitro-octane. Symmetric compounds will hav two ways of arriving at the same name.
## Linear alkanes
Straight-chain alkanes are sometimes indicated by the prefix n- (for normal) where a non-linear isomer exists. Although this is not strictly necessary, the usage is still common in cases where there is an important difference in properties between the straight-chain and branched-chain isomers: e.g. n-hexane or 2- or 3-methylpentane.
The first four members of the series (in terms of number of carbon atoms) are named as follows:
Alkanes with five or more carbon atoms are named by adding the suffix -ane to the appropriate numerical multiplier
with elision of a terminal -a- from the basic numerical term. Hence, pentane, C5H12; hexane, C6H14; heptane, C7H16; octane, C8H18; etc. For a more complete list, see List of alkanes.
## Branched alkanes
Simple branched alkanes often have a common name using a prefix to distinguish them from linear alkanes, for example n-pentane, isopentane, and neopentane.
Alternately, IUPAC naming conventions can be used to produce a systematic name.
The key steps in the naming of more complicate branched alkanes are as follows:
- Identify the longest linear chain of carbon atoms.
- Name this longest root chain using standard naming rules
- Name each side chain by changing the suffix of the name of the alkane from "-ane" to "-yl"
- Number the root chain so that sum total of the numbers assigned to each side group will be as low as possible.
- Number and name the side chains before the name of the root chain
- If there are multiple side chains of the same type, use prefixes such as "di-" and "tri-" to indicate it as such, and number each one.
## Cyclic alkanes
So-called cyclic alkanes are technically not alkanes, but cycloalkanes. They are hydrocarbons just like alkanes, but are containing one or more rings.
Simple cycloalkanes have a prefix "cyclo-" to distinguish them from alkanes. Cycloalkanes are named as per their acyclic counterparts with respect to the number of carbon atoms, e.g. cyclopentane (C5H10) is a cycloalkane with 5 carbon atoms just like pentane (C5H12), but they are joined up in a five-membered ring. Similarly, propane and cyclopropane, butane and cyclobutane, etc.
Substituted cycloalkanes are named similar to substituted alkanes — the cycloalkane ring is stated, and the substituents are according to their position on the ring, with the numbering decided by Cahn-Ingold-Prelog rules.
## Trivial names
The trivial (non-systematic) name for alkanes is "paraffins". Collectively, alkanes are known as the paraffin series. Trivial names for compounds are usually historical artifacts. They were coined before the development of systematic names, and have been retained due to familiar usage in industry. Cycloalkanes are also called naphthenes.
The term paraffins almost certainly stems from the petrochemical industry. Branched-chain alkanes are called isoparaffins. The use of the term "paraffin" is a general term and often does not distinguish between a pure compounds and mixtures of isomers with the same chemical formula (i.e. like a chemical anagram) e.g. pentane and isopentane.
The following trivial names are retained in the IUPAC system:
- isobutane for 2-methylpropane
- isopentane for 2-methylbutane
- neopentane for 2,2-dimethylpropane
# Occurrence
## Occurrence of alkanes in the Universe
Alkanes form a significant portion of the atmospheres of the outer gas planets such as Jupiter (0.1% methane, 0.0002% ethane), Saturn (0.2% methane, 0.0005% ethane), Uranus (1.99% methane, 0.00025% ethane) and Neptune (1.5% methane, 1.5 ppm ethane). Titan (1.6% methane), a satellite of Saturn, was examined by the Huygens probe which indicate that Titan's atmosphere periodically rains liquid methane onto the moon's surface. Also on Titan, a methane-spewing volcano was spotted and this volcanism is believed to be a significant source of the methane in the atmosphere. There also appear to be Methane/Ethane lakes near the north polar regions of Titan, as discovered by Cassini's radar imaging. Methane and ethane have also been detected in the tail of the comet Hyakutake. Chemical analysis showed that the abundances of ethane and methane were roughly equal, which is thought to imply that its ices formed in interstellar space, away from the Sun, which would have evaporated these volatile molecules.. Alkanes have also been detected in meteorites such as carbonaceous chondrites.
## Occurrence of alkanes on Earth
Traces of methane gas (about 0.0001% or 1 ppm) occur in the Earth's atmosphere, produced primarily by organisms such as Archaea, found for example in the gut of cows.
The most important commercial sources for alkanes are natural gas and oil. Natural gas contains primarily methane and ethane, with some propane and butane: oil is a mixture of liquid alkanes and other hydrocarbons. These hydrocarbons were formed when dead marine animals and plants (zooplankton and phytoplankton) died and sank to the bottom of ancient seas and were covered with sediments in an anoxic environment and converted over many millions of years at high temperatures and high pressure to their current form. Natural gas resulted thereby for example from the following reaction:
These hydrocarbons collected in porous rocks, located beneath an impermeable cap rock and so are trapped. Unlike methane, which is constantly reformed in large quantities, higher alkanes (alkanes with 9 or more carbon atoms) rarely develop to a considerable extent in nature. These deposits e.g. (oil fields) have formed over millions of years and once exhausted can not be readily replaced. The depletion of these hydrocarbons is the basis for what is known as the energy crisis.
Solid alkanes are known as tars and are formed when more volatile alkanes such as gases and oil evaporate from hydrocarbon deposits. One of the largest natural deposits of solid alkanes is in the asphalt lake known as the Pitch Lake in Trinidad and Tobago.
Methane is also present in what is called biogas, produced by animals and decaying matter, which is a possible renewable energy source.
Alkanes have a low solubility in water, so the content in the oceans is negligible: however, at high pressures and low temperatures (such as at the bottom of the oceans), methane can co-crystallize with water to form a solid methane hydrate. Although this cannot be commercially exploited at the present time, the amount of combustible energy of the known methane hydrate fields exceeds the energy content of all the natural gas and oil deposits put together;methane extracted from methane hydrate is considered therefore a candidate for future fuels.
## Biological occurrence
Although alkanes occur in nature in various way, they do not rank biologically among the essential materials. Cycloalkanes with 14 to 18 carbon atoms occur in musk, extracted from deer of the family Moschidae. All further information refers to (acyclic) alkanes.
Certain types of bacteria can metabolise alkanes: they prefer even-numbered carbon chains as they are easier to degrade than odd-numbered chains.
On the other hand certain archaea, the methanogens, produce large quantities of methane by the metabolism of carbon dioxide or other oxidised organic compounds. The energy is released by the oxidation of hydrogen:
Methanogens are also the producers of marsh gas in wetlands, and release about two billion tonnes of methane per year — the atmospheric content of this gas is produced nearly exclusively by them. The methane output of cattle and other herbivores, which can release up to 150 litres per day, and of termites, is also due to methanogens. They also produce this simplest of all alkanes in the intestines of humans. Methanogenic archaea are hence at the end of the carbon cycle, with carbon being released back into the atmosphere after having been fixed by photosynthesis. It is probable that our current deposits of natural gas were formed in a similar way.
Alkanes also play a role, if a minor role, in the biology of the three eukaryotic groups of organisms: fungi, plants and animals. Some specialised yeasts, e.g. Candida tropicale, Pichia sp., Rhodotorula sp., can use alkanes as a source of carbon and/or energy. The fungus Amorphotheca resinae prefers the longer-chain alkanes in aviation fuel, and can cause serious problems for aircraft in tropical regions.
In plants it is the solid long-chain alkanes that are found; they form a firm layer of wax, the cuticle, over areas of the plant exposed to the air. This protects the plant against water loss, while preventing the leaching of important minerals by the rain. It is also a protection against bacteria, fungi and harmful insects — the latter sink with their legs into the soft waxlike substance and have difficulty moving. The shining layer on fruits such as apples consists of long-chain alkanes. The carbon chains are usually between twenty and thirty carbon atoms in length and are made by the plants from fatty acids. The exact composition of the layer of wax is not only species-dependent, but changes also with the season and such environmental factors as lighting conditions, temperature or humidity.
Alkanes are found in animal products, although they are less important than unsaturated hydrocarbons. One example is the shark liver oil, which is approximately 14% pristane (2,6,10,14-tetramethylpentadecane, C19H40). Their occurrence is more important in pheromones, chemical messenger materials, on which above all insects are dependent for communication. With some kinds, as the support beetle Xylotrechus colonus, primarily pentacosane (C25H52), 3-methylpentaicosane (C26H54) and 9-methylpentaicosane (C26H54), they are transferred by body contact. With others like the tsetse fly Glossina morsitans morsitans, the pheromone contains the four alkanes 2-methylheptadecane (C18H38), 17,21-dimethylheptatriacontane (C39H80), 15,19-dimethylheptatriacontane (C39H80) and 15,19,23-trimethylheptatriacontane (C40H82), and
acts by smell over longer distances, a useful characteristic for pest control.
## Ecological relations
One example, in which both plant and animal alkanes play a role, is the ecological relationship between the sand bee (Andrena nigroaenea) and the early spider orchid (Ophrys sphegodes); the latter is dependent for pollination on the former. Sand bees use pheromones in order to identify a mate; in the case of A. nigroaenea, the females emit a mixture of tricosane (C23H48), pentacosane (C25H52) and heptacosane (C27H56) in the ratio 3:3:1, and males are attracted by specifically this odour. The orchid takes advantage of this mating arrangement to get the male bee to collect and disseminate its pollen; parts of its flower not only resemble the appearance of sand bees, but also produce large quantities of the three alkanes in the same ratio as female sand bees. As a result numerous males are lured to the blooms and attempt to copulate with their imaginary partner: although this endeavour is not crowned with success for the bee, it allows the orchid to transfer its pollen,
which will be dispersed after the departure of the frustrated male to different blooms.
# Production
## Petroleum refining
As stated earlier, the most important source of alkanes is natural gas and crude oil. Alkanes are separated in an oil refinery by fractional distillation and processed into many different products
## Fischer-Tropsch
The Fischer-Tropsch process is a method to synthesize liquid hydrocarbons, including alkanes, from carbon monoxide and hydrogen. This method is used to produce substitutes for petroleum distillates.
## Laboratory preparation
There is usually little need for alkanes to be synthesized in the laboratory, since they are usually commercially available. Also, alkanes are generally non-reactive chemically or biologically, and do not undergo functional group interconversions cleanly. When alkanes are produced in the laboratory, it is often a side product of a reaction. For example, the use of n-butyllithium as a strong base gives the conjugate acid, n-butane as a side product:
However, at times it may be desirable to make a portion of a molecule into an alkane like functionality (alkyl group) using the above or similar methods. For example an ethyl group is an alkyl group, when this is attached to a hydroxy group it gives ethanol, which is not an alkane. To do so, the best-known methods are hydrogenation of alkenes:
Alkanes or alkyl groups can also be prepared directly from alkyl halides in the Corey-House-Posner-Whitesides reaction. The Barton-McCombie deoxygenation removes hydroxyl groups from alcohols e.g.
and the Clemmensen reduction removes carbonyl groups from aldehydes and ketones to form alkanes or alkyl-substituted compounds e.g.:
# Applications
The applications of a certain alkane can be determined quite well according to the number of carbon atoms. The first four alkanes are used mainly for heating and cooking purposes, and in some countries for electricity generation. Methane and ethane are the main components of natural gas; they are normally stored as gases under pressure. It is however easier to transport them as liquids: this requires both compression and cooling of the gas.
Propane and butane can be liquefied at fairly low pressures, and are well known as liquified petroleum gas (LPG). Propane, for example, is used in the propane gas burner, butane in disposable cigarette lighters. The two alkanes are used as propellants in aerosol sprays.
From pentane to octane the alkanes are reasonably volatile liquids. They are used as fuels in internal combustion engines, as they vaporise easily on entry into the combustion chamber without forming droplets which would impair the unifomity of the combustion. Branched-chain alkanes are preferred, as they are much less prone to premature ignition which causes knocking than their straight-chain homologue. This propensity to premature ignition is measured by the octane rating of the fuel, where 2,2,4-trimethylpentane (isooctane) has an arbitrary value of 100 and heptane has a value of zero. Apart from their use as fuels, the middle alkanes are also good solvents for nonpolar substances.
Alkanes from nonane to, for instance, hexadecane (an alkane with sixteen carbon atoms) are liquids of higher viscosity, less and less suitable for use in gasoline. They form instead the major part of diesel and aviation fuel. Diesel fuels are characterised by their cetane number, cetane being an old name for hexadecane. However, the higher melting points of these alkanes can cause problems at low temperatures and in polar regions, where the fuel becomes too thick to flow correctly.
Alkanes from hexadecane upwards form the most important components of fuel oil and lubricating oil. In latter function they work at the same time as anti-corrosive agents, as their hydrophobic nature means that water cannot reach the metal surface. Many solid alkanes find use as paraffin wax, for example in candles. This should not be confused however with true wax, which consists primarily of esters.
Alkanes with a chain length of approximately 35 or more carbon atoms are found in bitumen, used for example in road surfacing. However, the higher alkanes have little value and are usually split into lower alkanes by cracking.
Some synthetic polymers such as polyethylene and polypropylene are alkanes with chains containing hundreds of thousands of carbon atoms. These materials are used in innumerable applications and billions of kilograms of these materials are made and used each year.
# Physical properties
### Boiling point
Alkanes experience inter-molecular van der Waals forces. Stronger inter-molecular van der Waals forces give rise to greater boiling points of alkanes.
There are two determinants for the strength of the van der Waals forces:
- the number of electrons surrounding the molecule, which increase with the alkane's molecular weight
- the surface area of the molecule
Under standard conditions, from CH4 to C4H10 alkanes are gaseous; from C5H12 to C17H36 they are liquids; and after C18H38 they are solids. As the boiling point of alkanes is primarily determined by weight, it should not be a surprise that the boiling point has almost a linear relationship with the size (molecular weight) of the molecule. As a rule of thumb, the boiling point rises 20 - 30 °C for each carbon added to the chain; this rule applies to other homologous series.
A straight-chain alkane will have a boiling point higher than a branched-chain alkane due to the greater surface area in contact, thus the greater van der Waals forces, between adjacent molecules. For example, compare isobutane and n-butane which boil at -12 and 0 °C, and 2,2-dimethylbutane and 2,3-dimethylbutane which boil at 50 and 58 °C respectively. For the latter case, two molecules 2,3-dimethylbutane can "lock" into each other better than the cross-shaped 2,2-dimethylbutane, hence the greater van der Waals forces.
On the other hand, cycloalkanes tend to have higher boiling points than their linear counterparts due to the locked conformations of the molecules which give a plane of intermolecular contact.
### Melting point
The melting points of the alkanes follow a similar trend to boiling points for the same reason as outlined above. That is, (all other things being equal) the larger the molecule the higher the melting point. There is one significant difference between boiling points and melting points. Solids have more ridged and fixed structure than liquids. This rigid structure requires energy to break down. Thus the stronger better put together solid structures will require more energy to break apart. For alkanes, this can be seen from the graph above (i.e. the blue line). The odd numbered alkanes have a lower trend in melting points that even numbered alkanes. This is because even numbered alkanes pack well in the solid phase, forming a well organised structure which requires more energy to break apart. The odd number alkanes pack less well and so the "looser" organised solid packing structure requires less energy to break apart.
The melting points of branched-chain alkanes can be either higher or lower than those of the corresponding straight-chain alkanes, again this depends on the ability of the alkane in question to packing well in the solid phase: this is particularly true for isoalkanes (2-methyl isomers), which often have melting points higher than those of the linear analogues.
### Conductivity
Alkanes do not conduct electricity, nor are they substantially polarized by an electric field. For this reason they do not form hydrogen bonds and are insoluble in polar solvents such as water. Since the hydrogen bonds between individual water molecules are aligned away from an alkane molecule, the coexistence of an alkane and water leads to an increase in molecular order (a reduction in entropy). As there is no significant bonding between water molecules and alkane molecules, the second law of thermodynamics suggests that this reduction in entropy should be minimised by minimising the contact between alkane and water: alkanes are said to be hydrophobic in that they repel water.
Their solubility in nonpolar solvents is relatively good, a property which is called lipophilicity. Different alkanes are, for example, miscible in all proportions among themselves.
The density of the alkanes usually increases with increasing number of carbon atoms, but remains less than that of water. Hence, alkanes form the upper layer in an alkane-water mixture.
## Molecular geometry
The molecular structure of the alkanes directly affects their physical and chemical characteristics. It is derived from the electron configuration of carbon, which has four valence electrons. The carbon atoms in alkanes are always sp3 hybridised, that is to say that the valence electrons are said to be in four equivalent orbitals derived from the combination of the 2s orbital and the three 2p orbitals. These orbitals, which have identical energies, are arranged spatially in the form of a tetrahedron, the angle of cos−1(−⅓) ≈ 109.47° between them.
## Bond lengths and bond angles
An alkane molecule has only C – H and C – C single bonds. The former result from the overlap of a sp³-orbital of carbon with the 1s-orbital of a hydrogen; the latter by the overlap of two sp³-orbitals on different carbon atoms. The bond lengths amount to 1.09×10−10 m for a C – H bond and 1.54×10−10 m for a C – C bond.
The spatial arrangement of the bonds is similar to that of the four sp³-orbitals — they are tetrahedrally arranged, with an angle of 109.47° between them. Structural formulae which represent the bonds as being at right angles to one another, while both common and useful, do not correspond with the reality.
## Conformation
The structural formula and the bond angles are not usually sufficient to completely describe the geometry of a molecule. There is a further degree of freedom for each carbon – carbon bond: the torsion angle between the atoms or groups bound to the atoms at each end of the bond. The spatial arrangement described by the torsion angles of the molecule is known as its conformation.
Ethane forms the simplest case for studying the conformation of alkanes, as there is only one C – C bond. If one looks down the axis of the C – C bond, then one will see the so-called Newman projection. The hydrogen atoms on both the front and rear carbon atoms have an angle of 120° between them, resulting from the projection of the base of the tetrahedron onto a flat plane. However, the torsion angle between a given hydrogen atom attached to the front carbon and a given hydrogen atom attached to the rear carbon can vary freely between 0° and 360°. This is a consequence of the free rotation about a carbon – carbon single bond. Despite this apparent freedom, only two limiting conformations are important: eclipsed conformation and staggered conformation.
The two conformations, also known as rotamers, differ in energy: The staggered conformation is 12.6 kJ/mol lower in energy (more stable) than the eclipsed conformation (the least stable).
This difference in energy between the two conformations, known as the torsion energy, is low compared to the thermal energy of an ethane molecule at ambient temperature. There is constant rotation about the C-C bond. The time taken for an ethane molecule to pass from one staggered conformation to the next, equivalent to the rotation of one CH3-group by 120° relative to the other, is of the order of 10−11 seconds.
The case of higher alkanes is more complex but based on similar principles, with the antiperiplanar conformation always being the most favoured around each carbon-carbon bond. For this reason, alkanes are usually shown in a zigzag arrangement in diagrams or in models. The actual structure will always differ somewhat from these idealised forms, as the differences in energy between the conformations are small compared to the thermal energy of the molecules: alkane molecules have no fixed structural form, whatever the models may suggest.
## Spectroscopic properties
Virtually all organic compounds contain carbon – carbon and carbon – hydrogen bonds, and so show some of the features of alkanes in their spectra. Alkanes are notable for having no other groups, and therefore for the absence of other characteristic spectroscopic features.
### Infrared spectroscopy
The carbon – hydrogen stretching mode gives a strong absorption between 2850 and 2960 nanometres, while the carbon – carbon stretching mode absorbs between 800 and 1300 nm. The carbon – hydrogen bending modes depend on the nature of the group: methyl groups show bands at 1450 nm and 1375 nm, while methylene groups show bands at 1465 nm and 1450 nm. Carbon chains with more than four carbon atoms show a weak absorption at around 725 nm.
### NMR spectroscopy
The proton resonances of alkanes are usually found at δH = 0.5 – 1.5. The carbon-13 resonances depend on the number of hydrogen atoms attached to the carbon: δC = 8 – 30 (primary, methyl, -CH3), 15 – 55 (secondary, methylene, -CH2-), 20 – 60 (tertiary, methyne, C-H) and quaternary. The carbon-13 resonance of quaternary carbon atoms is characteristically weak, due to the lack of Nuclear Overhauser effect and the long relaxation time, and can be missed in weak samples, or sample that have not been run for a sufficiently long time.
### Mass spectrometry
Alkanes have a high ionisation energy, and the molecular ion is usually weak. The fragmentation pattern can be difficult to interpret, but, in the case of branched chain alkanes, the carbon chain is preferentially cleaved at tertiary or quaternary carbons due to the relative stability of the resulting free radicals. The fragment resulting from the loss of a single methyl group (M−15) is often absent, and other fragment are often spaced by intervals of fourteen mass units, corresponding to sequential loss of CH2-groups.
# Chemical properties
Alkanes generally show a relatively low reactivity, because their C bonds are relatively stable and cannot be easily broken. Unlike most other organic compounds, they possess no functional groups.
They react only very poorly with ionic or other polar substances. The acid dissociation constant (pKa) values of all alkanes are above 60, hence they are practically inert to acids and bases (see: carbon acids). This inertness is the source of the term paraffins (with the meaning here of "lacking affinity"). In crude oil the alkane molecules have remained chemically unchanged for millions of years.
However redox reactions of alkanes, in particular with oxygen and the halogens, are possible as the carbon atoms are in a strongly reduced condition; in the case of methane, the lowest possible oxidation state for carbon (−4) is reached. Reaction with oxygen leads to combustion without any smoke; with halogens, substitution. In addition, alkanes have been shown to interact with, and bind to, certain transition metal complexes in (See: carbon-hydrogen bond activation).
Free radicals, molecules with unpaired electrons, play a large role in most reactions of alkanes, such as cracking and reformation where long-chain alkanes are converted into shorter-chain alkanes and straight-chain alkanes into branched-chain isomers.
In highly branched alkanes, the bond angle may differ significantly from the optimal value (109.5°) in order to allow the different groups sufficient space. This causes a tension in the molecule, known as steric hindrance, and can substantially increase the reactivity.
## Reactions with oxygen
All alkanes react with oxygen in a combustion reaction, although they become increasingly difficult to ignite as the number of carbon atoms increases. The general equation for complete combustion is:
In the absence of sufficient oxygen, carbon monoxide or even soot can be formed, as shown below:
for example methane:
See the alkane heat of formation table for detailed data.
The standard enthalpy change of combustion, ΔcHo, for alkanes increases by about 650 kJ/mol per CH2 group. Branched-chain alkanes have lower values of ΔcHo than straight-chain alkanes of the same number of carbon atoms, and so can be seen to be somewhat more stable.
## Reactions with halogens
Alkanes react with halogens in a so-called free radical halogenation reaction. The hydrogen atoms of the alkane are progressively replaced by halogen atoms. Free radicals are the reactive species which participate in the reaction, which usually leads to a mixture of products. The reaction is highly exothermic, and can lead to an explosion.
These reactions are an important industrial route to halogenated hydrocarbons. There are three steps:
- Initiation the halogen radicals form by homolysis. Usually, energy in the form of heat or light is required.
- Chain reaction then takes place — the halogen radical abstracts a hydrogen from the alkane to give an alkyl radical. This reacts further.
- 'Chain termination where step the radicals recombine.
Experiments have shown that all halogenation produces a mixture of all possible isomers, indicating that all hydrogen atoms are susceptible to reaction. The mixture produced, however, is not a statistical mixture: secondary and tertiary hydrogen atoms are preferentially replaced due to the greater stability of secondary and tertiary free radicals. An example can be seen in the monobromination of propane:
## Cracking
Cracking breaks larger molecules into smaller ones. This can be done with a thermal or catalytic method. The thermal cracking process follows a homolytic mechanism, that is, bonds break symmetrically and thus pairs of free radicals are formed. The catalytic cracking process involves the presence of acid catalysts (usually solid acids such as silica-alumina and zeolites) which promote a heterolytic (asymmetric) breakage of bonds yielding pairs of ions of opposite charges, usually a carbocation and the very unstable hydride anion. Carbon-localized free radicals and cations are both highly unstable and undergo processes of chain rearrangement, C-C scission in position beta (i.e., cracking) and intra- and intermolecular hydrogen transfer or hydride transfer. In both types of processes, the corresponding reactive intermediates (radicals, ions) are permanently regenerated, and thus they proceed by a
self-propagating chain mechanism. The chain of reactions is eventually terminated by radical or ion recombination.
Here is an example of cracking with butane CH3-CH2-CH2-CH3
- 1st possibility (48%): breaking is done on the CH3-CH2 bond.
CH3- / *CH2-CH2-CH3
after a certain number of steps, we will obtain an alkane and an alkene:
CH4 + CH2=CH-CH3
- 2nd possibility (38%): breaking is done on the CH2-CH2 bond.
CH3-CH2- / *CH2-CH3
after a certain number of steps, we will obtain an alkane and an alkene
from different types: CH3-CH3 + CH2=CH2
- 3rd possibility (14%): breaking of a C-H bond
after a certain number of steps, we will obtain an alkene and hydrogen gas: CH2=CH-CH2-CH3 + H2
## Isomerization and reformation
Isomerization and reformation are processes in which straight-chain alkanes are heated in the presence of a platinum catalyst. In isomerization, the alkanes become branched-chain isomers. In reformation, the alkanes become cycloalkanes or aromatic hydrocarbons, giving off hydrogen as a by-product. Both of these processes raise the octane number of the substance.
## Other reactions
Alkanes will react with steam in the presence of a nickel catalyst to give hydrogen. Alkanes can by chlorosulfonated and nitrated, although both reactions require special conditions. The fermentation of alkanes to carboxylic acids is of some technical importance. In the Reed reaction, sulfur dioxide, chlorine and light convert hydrocarbons to sulfonyl chlorides.
# Hazards
Methane is explosive when mixed with air (1 – 8% CH4) and is a strong greenhouse gas: other lower alkanes can also form explosive mixtures with air. The lighter liquid alkanes are highly flammable, although this risk decreases with the length of the carbon chain. Pentane, hexane, heptane and octane are classed as dangerous for the environment and harmful. The straight chain isomer of hexane is a neurotoxin, and therefore rarely used commercially. | Alkane
# Overview
Alkanes, also known as Paraffins, are chemical compounds that consist only of the elements carbon (C) and hydrogen (H) (i.e. hydrocarbons), where each of these atoms are linked together exclusively by single bonds (i.e. they are saturated compounds) without any cyclic structure (i.e. loops). Alkanes belong to a homologous series of organic compounds in which the members differ by a constant relative atomic mass of 14.
Each carbon atom must have 4 bonds (either C-H or C-C bonds), and each hydrogen atom must be joined to a carbon atom (H-C bonds). A series of linked carbon atoms is known as the carbon skeleton or carbon backbone. Typically the number of carbon atoms is often used to define the size of the alkane (e.g. C2-alkane).
An alkyl group is a functional group or side chain which, like an alkane, consists solely of singly bonded carbon and hydrogen atoms, for example a methyl or ethyl group.
Saturated hydrocarbons can be linear (general formula CnH2n+2) where the carbon atoms are joined in a snake-like structure, branched (general formula CnH2n+2, n>3) where the carbon backbone splits off in one or more directions, or cyclic (general formula CnH2n, n>2) where the carbon backbone is linked so as to form a loop. According to the definition by IUPAC, the former two are alkanes, while the third group is called cycloalkanes.[1] In other words, saturated hydrocarbons are divided into alkanes and cycloalkanes, depending on whether or not they have cyclic structures, and technically, cycloalkanes are not alkanes. However, cycloalkanes are sometimes called cyclic alkanes, confusingly, when "real" alkanes are called acyclic alkanes. Saturated hydrocarbons can also combine any of the linear, cyclic (e.g. polycyclic) and branching structures, and they are still alkanes (no general formula) as long as they are acyclic (i.e. having no loops).
The simplest possible alkane (the parent molecule) is methane, CH4. There is no limit to the number of carbon atoms that can be linked together, the only limitation being that the molecule is acyclic, is saturated, and is a hydrocarbon. Saturated oils and waxes are examples of larger alkanes where the number of carbons in the carbon backbone tends to be greater than 10.
Alkanes are not very reactive and have little biological activity. Alkanes can be viewed as a molecular scaffold upon which can be hung the interesting biologically active/reactive portions (functional groups) of the molecule.
# Isomerism
Alkanes with more than three carbon atoms can be arranged in a multiple number of ways, forming different structural isomers. An isomer is like a chemical anagram, in which the atoms of a chemical compound are arranged or joined together in a different order. The simplest isomer of an alkane is the one in which the carbon atoms are arranged in a single chain with no branches. This isomer is sometimes called the n-isomer (n for "normal", although it is not necessarily the most common). However the chain of carbon atoms may also be branched at one or more points. The number of possible isomers increases rapidly with the number of carbon atoms. For example:
- C1: 1 isomer — methane
- C2: 1 isomer — ethane
- C3: 1 isomers — propane
- C4: 2 isomers — n-butane, isobutane
- C12: 355 isomers
- C32: 27,711,253,769 isomers
- C60: 22,158,734,535,770,411,074,184 isomers
In addition to these isomers, the chain of carbon atoms may form one or more loops. Such compounds are called cycloalkanes.
# Nomenclature
The IUPAC nomenclature (systematic way of naming compounds) for alkanes is based on identifying hydrocarbon chains. Unbranched, saturated hydrocarbon chains are named systematically with a Greek numerical prefix denoting the number of carbons and the suffix "-ane".[2]
August Wilhelm von Hofmann suggested systematizing nomenclature by using the whole sequence of vowels a, e, i, o and u to create suffixes -ane, -ene, -ine (or -yne), -one, -une, for the hydrocarbons. The first three name hydrocarbons with single, double and triple bonds. "-one" represents a ketone. "-ol" represents an alcohol or OH group. "-oxy-" means an ether and refers to oxygen between two carbons, so that methoxy-methane is the IUPAC name for dimethyl ether.
It is difficult or impossible to find compounds with more than one IUPAC name. This is because shorter chains attached to longer chains are prefixes and the convention includes brackets. Numbers in the name, referring to which carbon a group is attached to, should be as low as possible, so that 1- is implied and usually omitted from names of organic compounds with only one side-group. "1-" is implied in Nitro-octane. Symmetric compounds will hav two ways of arriving at the same name.
## Linear alkanes
Straight-chain alkanes are sometimes indicated by the prefix n- (for normal) where a non-linear isomer exists. Although this is not strictly necessary, the usage is still common in cases where there is an important difference in properties between the straight-chain and branched-chain isomers: e.g. n-hexane or 2- or 3-methylpentane.
The first four members of the series (in terms of number of carbon atoms) are named as follows:
Alkanes with five or more carbon atoms are named by adding the suffix -ane to the appropriate numerical multiplier[3]
with elision of a terminal -a- from the basic numerical term. Hence, pentane, C5H12; hexane, C6H14; heptane, C7H16; octane, C8H18; etc. For a more complete list, see List of alkanes.
## Branched alkanes
Simple branched alkanes often have a common name using a prefix to distinguish them from linear alkanes, for example n-pentane, isopentane, and neopentane.
Alternately, IUPAC naming conventions can be used to produce a systematic name.
The key steps in the naming of more complicate branched alkanes are as follows:[4]
- Identify the longest linear chain of carbon atoms.
- Name this longest root chain using standard naming rules
- Name each side chain by changing the suffix of the name of the alkane from "-ane" to "-yl"
- Number the root chain so that sum total of the numbers assigned to each side group will be as low as possible.
- Number and name the side chains before the name of the root chain
- If there are multiple side chains of the same type, use prefixes such as "di-" and "tri-" to indicate it as such, and number each one.
## Cyclic alkanes
So-called cyclic alkanes are technically not alkanes, but cycloalkanes. They are hydrocarbons just like alkanes, but are containing one or more rings.
Simple cycloalkanes have a prefix "cyclo-" to distinguish them from alkanes. Cycloalkanes are named as per their acyclic counterparts with respect to the number of carbon atoms, e.g. cyclopentane (C5H10) is a cycloalkane with 5 carbon atoms just like pentane (C5H12), but they are joined up in a five-membered ring. Similarly, propane and cyclopropane, butane and cyclobutane, etc.
Substituted cycloalkanes are named similar to substituted alkanes — the cycloalkane ring is stated, and the substituents are according to their position on the ring, with the numbering decided by Cahn-Ingold-Prelog rules.[3]
## Trivial names
The trivial (non-systematic) name for alkanes is "paraffins". Collectively, alkanes are known as the paraffin series. Trivial names for compounds are usually historical artifacts. They were coined before the development of systematic names, and have been retained due to familiar usage in industry. Cycloalkanes are also called naphthenes.
The term paraffins almost certainly stems from the petrochemical industry. Branched-chain alkanes are called isoparaffins. The use of the term "paraffin" is a general term and often does not distinguish between a pure compounds and mixtures of isomers with the same chemical formula (i.e. like a chemical anagram) e.g. pentane and isopentane.
The following trivial names are retained in the IUPAC system:
- isobutane for 2-methylpropane
- isopentane for 2-methylbutane
- neopentane for 2,2-dimethylpropane
# Occurrence
## Occurrence of alkanes in the Universe
Alkanes form a significant portion of the atmospheres of the outer gas planets such as Jupiter (0.1% methane, 0.0002% ethane), Saturn (0.2% methane, 0.0005% ethane), Uranus (1.99% methane, 0.00025% ethane) and Neptune (1.5% methane, 1.5 ppm ethane). Titan (1.6% methane), a satellite of Saturn, was examined by the Huygens probe which indicate that Titan's atmosphere periodically rains liquid methane onto the moon's surface.[5] Also on Titan, a methane-spewing volcano was spotted and this volcanism is believed to be a significant source of the methane in the atmosphere. There also appear to be Methane/Ethane lakes near the north polar regions of Titan, as discovered by Cassini's radar imaging. Methane and ethane have also been detected in the tail of the comet Hyakutake. Chemical analysis showed that the abundances of ethane and methane were roughly equal, which is thought to imply that its ices formed in interstellar space, away from the Sun, which would have evaporated these volatile molecules.[6]. Alkanes have also been detected in meteorites such as carbonaceous chondrites.
## Occurrence of alkanes on Earth
Traces of methane gas (about 0.0001% or 1 ppm) occur in the Earth's atmosphere, produced primarily by organisms such as Archaea, found for example in the gut of cows.
The most important commercial sources for alkanes are natural gas and oil.[7] Natural gas contains primarily methane and ethane, with some propane and butane: oil is a mixture of liquid alkanes and other hydrocarbons. These hydrocarbons were formed when dead marine animals and plants (zooplankton and phytoplankton) died and sank to the bottom of ancient seas and were covered with sediments in an anoxic environment and converted over many millions of years at high temperatures and high pressure to their current form. Natural gas resulted thereby for example from the following reaction:
These hydrocarbons collected in porous rocks, located beneath an impermeable cap rock and so are trapped. Unlike methane, which is constantly reformed in large quantities, higher alkanes (alkanes with 9 or more carbon atoms) rarely develop to a considerable extent in nature. These deposits e.g. (oil fields) have formed over millions of years and once exhausted can not be readily replaced. The depletion of these hydrocarbons is the basis for what is known as the energy crisis.
Solid alkanes are known as tars and are formed when more volatile alkanes such as gases and oil evaporate from hydrocarbon deposits. One of the largest natural deposits of solid alkanes is in the asphalt lake known as the Pitch Lake in Trinidad and Tobago.
Methane is also present in what is called biogas, produced by animals and decaying matter, which is a possible renewable energy source.
Alkanes have a low solubility in water, so the content in the oceans is negligible: however, at high pressures and low temperatures (such as at the bottom of the oceans), methane can co-crystallize with water to form a solid methane hydrate. Although this cannot be commercially exploited at the present time, the amount of combustible energy of the known methane hydrate fields exceeds the energy content of all the natural gas and oil deposits put together;methane extracted from methane hydrate is considered therefore a candidate for future fuels.
## Biological occurrence
Although alkanes occur in nature in various way, they do not rank biologically among the essential materials. Cycloalkanes with 14 to 18 carbon atoms occur in musk, extracted from deer of the family Moschidae. All further information refers to (acyclic) alkanes.
Certain types of bacteria can metabolise alkanes: they prefer even-numbered carbon chains as they are easier to degrade than odd-numbered chains.
On the other hand certain archaea, the methanogens, produce large quantities of methane by the metabolism of carbon dioxide or other oxidised organic compounds. The energy is released by the oxidation of hydrogen:
Methanogens are also the producers of marsh gas in wetlands, and release about two billion tonnes of methane per year — the atmospheric content of this gas is produced nearly exclusively by them. The methane output of cattle and other herbivores, which can release up to 150 litres per day, and of termites, is also due to methanogens. They also produce this simplest of all alkanes in the intestines of humans. Methanogenic archaea are hence at the end of the carbon cycle, with carbon being released back into the atmosphere after having been fixed by photosynthesis. It is probable that our current deposits of natural gas were formed in a similar way.
Alkanes also play a role, if a minor role, in the biology of the three eukaryotic groups of organisms: fungi, plants and animals. Some specialised yeasts, e.g. Candida tropicale, Pichia sp., Rhodotorula sp., can use alkanes as a source of carbon and/or energy. The fungus Amorphotheca resinae prefers the longer-chain alkanes in aviation fuel, and can cause serious problems for aircraft in tropical regions.
In plants it is the solid long-chain alkanes that are found; they form a firm layer of wax, the cuticle, over areas of the plant exposed to the air. This protects the plant against water loss, while preventing the leaching of important minerals by the rain. It is also a protection against bacteria, fungi and harmful insects — the latter sink with their legs into the soft waxlike substance and have difficulty moving. The shining layer on fruits such as apples consists of long-chain alkanes. The carbon chains are usually between twenty and thirty carbon atoms in length and are made by the plants from fatty acids. The exact composition of the layer of wax is not only species-dependent, but changes also with the season and such environmental factors as lighting conditions, temperature or humidity.
Alkanes are found in animal products, although they are less important than unsaturated hydrocarbons. One example is the shark liver oil, which is approximately 14% pristane (2,6,10,14-tetramethylpentadecane, C19H40). Their occurrence is more important in pheromones, chemical messenger materials, on which above all insects are dependent for communication. With some kinds, as the support beetle Xylotrechus colonus, primarily pentacosane (C25H52), 3-methylpentaicosane (C26H54) and 9-methylpentaicosane (C26H54), they are transferred by body contact. With others like the tsetse fly Glossina morsitans morsitans, the pheromone contains the four alkanes 2-methylheptadecane (C18H38), 17,21-dimethylheptatriacontane (C39H80), 15,19-dimethylheptatriacontane (C39H80) and 15,19,23-trimethylheptatriacontane (C40H82), and
acts by smell over longer distances, a useful characteristic for pest control.
## Ecological relations
One example, in which both plant and animal alkanes play a role, is the ecological relationship between the sand bee (Andrena nigroaenea) and the early spider orchid (Ophrys sphegodes); the latter is dependent for pollination on the former. Sand bees use pheromones in order to identify a mate; in the case of A. nigroaenea, the females emit a mixture of tricosane (C23H48), pentacosane (C25H52) and heptacosane (C27H56) in the ratio 3:3:1, and males are attracted by specifically this odour. The orchid takes advantage of this mating arrangement to get the male bee to collect and disseminate its pollen; parts of its flower not only resemble the appearance of sand bees, but also produce large quantities of the three alkanes in the same ratio as female sand bees. As a result numerous males are lured to the blooms and attempt to copulate with their imaginary partner: although this endeavour is not crowned with success for the bee, it allows the orchid to transfer its pollen,
which will be dispersed after the departure of the frustrated male to different blooms.
# Production
## Petroleum refining
As stated earlier, the most important source of alkanes is natural gas and crude oil.[7] Alkanes are separated in an oil refinery by fractional distillation and processed into many different products
## Fischer-Tropsch
The Fischer-Tropsch process is a method to synthesize liquid hydrocarbons, including alkanes, from carbon monoxide and hydrogen. This method is used to produce substitutes for petroleum distillates.
## Laboratory preparation
There is usually little need for alkanes to be synthesized in the laboratory, since they are usually commercially available. Also, alkanes are generally non-reactive chemically or biologically, and do not undergo functional group interconversions cleanly. When alkanes are produced in the laboratory, it is often a side product of a reaction. For example, the use of n-butyllithium as a strong base gives the conjugate acid, n-butane as a side product:
However, at times it may be desirable to make a portion of a molecule into an alkane like functionality (alkyl group) using the above or similar methods. For example an ethyl group is an alkyl group, when this is attached to a hydroxy group it gives ethanol, which is not an alkane. To do so, the best-known methods are hydrogenation of alkenes:
Alkanes or alkyl groups can also be prepared directly from alkyl halides in the Corey-House-Posner-Whitesides reaction. The Barton-McCombie deoxygenation[8][9] removes hydroxyl groups from alcohols e.g.
and the Clemmensen reduction[10][11][12][13] removes carbonyl groups from aldehydes and ketones to form alkanes or alkyl-substituted compounds e.g.:
# Applications
The applications of a certain alkane can be determined quite well according to the number of carbon atoms. The first four alkanes are used mainly for heating and cooking purposes, and in some countries for electricity generation. Methane and ethane are the main components of natural gas; they are normally stored as gases under pressure. It is however easier to transport them as liquids: this requires both compression and cooling of the gas.
Propane and butane can be liquefied at fairly low pressures, and are well known as liquified petroleum gas (LPG). Propane, for example, is used in the propane gas burner, butane in disposable cigarette lighters. The two alkanes are used as propellants in aerosol sprays.
From pentane to octane the alkanes are reasonably volatile liquids. They are used as fuels in internal combustion engines, as they vaporise easily on entry into the combustion chamber without forming droplets which would impair the unifomity of the combustion. Branched-chain alkanes are preferred, as they are much less prone to premature ignition which causes knocking than their straight-chain homologue. This propensity to premature ignition is measured by the octane rating of the fuel, where 2,2,4-trimethylpentane (isooctane) has an arbitrary value of 100 and heptane has a value of zero. Apart from their use as fuels, the middle alkanes are also good solvents for nonpolar substances.
Alkanes from nonane to, for instance, hexadecane (an alkane with sixteen carbon atoms) are liquids of higher viscosity, less and less suitable for use in gasoline. They form instead the major part of diesel and aviation fuel. Diesel fuels are characterised by their cetane number, cetane being an old name for hexadecane. However, the higher melting points of these alkanes can cause problems at low temperatures and in polar regions, where the fuel becomes too thick to flow correctly.
Alkanes from hexadecane upwards form the most important components of fuel oil and lubricating oil. In latter function they work at the same time as anti-corrosive agents, as their hydrophobic nature means that water cannot reach the metal surface. Many solid alkanes find use as paraffin wax, for example in candles. This should not be confused however with true wax, which consists primarily of esters.
Alkanes with a chain length of approximately 35 or more carbon atoms are found in bitumen, used for example in road surfacing. However, the higher alkanes have little value and are usually split into lower alkanes by cracking.
Some synthetic polymers such as polyethylene and polypropylene are alkanes with chains containing hundreds of thousands of carbon atoms. These materials are used in innumerable applications and billions of kilograms of these materials are made and used each year.
# Physical properties
### Boiling point
Alkanes experience inter-molecular van der Waals forces. Stronger inter-molecular van der Waals forces give rise to greater boiling points of alkanes.[7]
There are two determinants for the strength of the van der Waals forces:
- the number of electrons surrounding the molecule, which increase with the alkane's molecular weight
- the surface area of the molecule
Under standard conditions, from CH4 to C4H10 alkanes are gaseous; from C5H12 to C17H36 they are liquids; and after C18H38 they are solids. As the boiling point of alkanes is primarily determined by weight, it should not be a surprise that the boiling point has almost a linear relationship with the size (molecular weight) of the molecule. As a rule of thumb, the boiling point rises 20 - 30 °C for each carbon added to the chain; this rule applies to other homologous series.[7]
A straight-chain alkane will have a boiling point higher than a branched-chain alkane due to the greater surface area in contact, thus the greater van der Waals forces, between adjacent molecules. For example, compare isobutane and n-butane which boil at -12 and 0 °C, and 2,2-dimethylbutane and 2,3-dimethylbutane which boil at 50 and 58 °C respectively.[7] For the latter case, two molecules 2,3-dimethylbutane can "lock" into each other better than the cross-shaped 2,2-dimethylbutane, hence the greater van der Waals forces.
On the other hand, cycloalkanes tend to have higher boiling points than their linear counterparts due to the locked conformations of the molecules which give a plane of intermolecular contact.
### Melting point
The melting points of the alkanes follow a similar trend to boiling points for the same reason as outlined above. That is, (all other things being equal) the larger the molecule the higher the melting point. There is one significant difference between boiling points and melting points. Solids have more ridged and fixed structure than liquids. This rigid structure requires energy to break down. Thus the stronger better put together solid structures will require more energy to break apart. For alkanes, this can be seen from the graph above (i.e. the blue line). The odd numbered alkanes have a lower trend in melting points that even numbered alkanes. This is because even numbered alkanes pack well in the solid phase, forming a well organised structure which requires more energy to break apart. The odd number alkanes pack less well and so the "looser" organised solid packing structure requires less energy to break apart. [14]
The melting points of branched-chain alkanes can be either higher or lower than those of the corresponding straight-chain alkanes, again this depends on the ability of the alkane in question to packing well in the solid phase: this is particularly true for isoalkanes (2-methyl isomers), which often have melting points higher than those of the linear analogues.
### Conductivity
Alkanes do not conduct electricity, nor are they substantially polarized by an electric field. For this reason they do not form hydrogen bonds and are insoluble in polar solvents such as water. Since the hydrogen bonds between individual water molecules are aligned away from an alkane molecule, the coexistence of an alkane and water leads to an increase in molecular order (a reduction in entropy). As there is no significant bonding between water molecules and alkane molecules, the second law of thermodynamics suggests that this reduction in entropy should be minimised by minimising the contact between alkane and water: alkanes are said to be hydrophobic in that they repel water.
Their solubility in nonpolar solvents is relatively good, a property which is called lipophilicity. Different alkanes are, for example, miscible in all proportions among themselves.
The density of the alkanes usually increases with increasing number of carbon atoms, but remains less than that of water. Hence, alkanes form the upper layer in an alkane-water mixture.
## Molecular geometry
The molecular structure of the alkanes directly affects their physical and chemical characteristics. It is derived from the electron configuration of carbon, which has four valence electrons. The carbon atoms in alkanes are always sp3 hybridised, that is to say that the valence electrons are said to be in four equivalent orbitals derived from the combination of the 2s orbital and the three 2p orbitals. These orbitals, which have identical energies, are arranged spatially in the form of a tetrahedron, the angle of cos−1(−⅓) ≈ 109.47° between them.
## Bond lengths and bond angles
An alkane molecule has only C – H and C – C single bonds. The former result from the overlap of a sp³-orbital of carbon with the 1s-orbital of a hydrogen; the latter by the overlap of two sp³-orbitals on different carbon atoms. The bond lengths amount to 1.09×10−10 m for a C – H bond and 1.54×10−10 m for a C – C bond.
The spatial arrangement of the bonds is similar to that of the four sp³-orbitals — they are tetrahedrally arranged, with an angle of 109.47° between them. Structural formulae which represent the bonds as being at right angles to one another, while both common and useful, do not correspond with the reality.
## Conformation
The structural formula and the bond angles are not usually sufficient to completely describe the geometry of a molecule. There is a further degree of freedom for each carbon – carbon bond: the torsion angle between the atoms or groups bound to the atoms at each end of the bond. The spatial arrangement described by the torsion angles of the molecule is known as its conformation.
Ethane forms the simplest case for studying the conformation of alkanes, as there is only one C – C bond. If one looks down the axis of the C – C bond, then one will see the so-called Newman projection. The hydrogen atoms on both the front and rear carbon atoms have an angle of 120° between them, resulting from the projection of the base of the tetrahedron onto a flat plane. However, the torsion angle between a given hydrogen atom attached to the front carbon and a given hydrogen atom attached to the rear carbon can vary freely between 0° and 360°. This is a consequence of the free rotation about a carbon – carbon single bond. Despite this apparent freedom, only two limiting conformations are important: eclipsed conformation and staggered conformation.
The two conformations, also known as rotamers, differ in energy: The staggered conformation is 12.6 kJ/mol lower in energy (more stable) than the eclipsed conformation (the least stable).
This difference in energy between the two conformations, known as the torsion energy, is low compared to the thermal energy of an ethane molecule at ambient temperature. There is constant rotation about the C-C bond. The time taken for an ethane molecule to pass from one staggered conformation to the next, equivalent to the rotation of one CH3-group by 120° relative to the other, is of the order of 10−11 seconds.
The case of higher alkanes is more complex but based on similar principles, with the antiperiplanar conformation always being the most favoured around each carbon-carbon bond. For this reason, alkanes are usually shown in a zigzag arrangement in diagrams or in models. The actual structure will always differ somewhat from these idealised forms, as the differences in energy between the conformations are small compared to the thermal energy of the molecules: alkane molecules have no fixed structural form, whatever the models may suggest.
## Spectroscopic properties
Virtually all organic compounds contain carbon – carbon and carbon – hydrogen bonds, and so show some of the features of alkanes in their spectra. Alkanes are notable for having no other groups, and therefore for the absence of other characteristic spectroscopic features.
### Infrared spectroscopy
The carbon – hydrogen stretching mode gives a strong absorption between 2850 and 2960 nanometres, while the carbon – carbon stretching mode absorbs between 800 and 1300 nm. The carbon – hydrogen bending modes depend on the nature of the group: methyl groups show bands at 1450 nm and 1375 nm, while methylene groups show bands at 1465 nm and 1450 nm. Carbon chains with more than four carbon atoms show a weak absorption at around 725 nm.
### NMR spectroscopy
The proton resonances of alkanes are usually found at δH = 0.5 – 1.5. The carbon-13 resonances depend on the number of hydrogen atoms attached to the carbon: δC = 8 – 30 (primary, methyl, -CH3), 15 – 55 (secondary, methylene, -CH2-), 20 – 60 (tertiary, methyne, C-H) and quaternary. The carbon-13 resonance of quaternary carbon atoms is characteristically weak, due to the lack of Nuclear Overhauser effect and the long relaxation time, and can be missed in weak samples, or sample that have not been run for a sufficiently long time.
### Mass spectrometry
Alkanes have a high ionisation energy, and the molecular ion is usually weak. The fragmentation pattern can be difficult to interpret, but, in the case of branched chain alkanes, the carbon chain is preferentially cleaved at tertiary or quaternary carbons due to the relative stability of the resulting free radicals. The fragment resulting from the loss of a single methyl group (M−15) is often absent, and other fragment are often spaced by intervals of fourteen mass units, corresponding to sequential loss of CH2-groups.
# Chemical properties
Alkanes generally show a relatively low reactivity, because their C bonds are relatively stable and cannot be easily broken. Unlike most other organic compounds, they possess no functional groups.
They react only very poorly with ionic or other polar substances. The acid dissociation constant (pKa) values of all alkanes are above 60, hence they are practically inert to acids and bases (see: carbon acids). This inertness is the source of the term paraffins (with the meaning here of "lacking affinity"). In crude oil the alkane molecules have remained chemically unchanged for millions of years.
However redox reactions of alkanes, in particular with oxygen and the halogens, are possible as the carbon atoms are in a strongly reduced condition; in the case of methane, the lowest possible oxidation state for carbon (−4) is reached. Reaction with oxygen leads to combustion without any smoke; with halogens, substitution. In addition, alkanes have been shown to interact with, and bind to, certain transition metal complexes in (See: carbon-hydrogen bond activation).
Free radicals, molecules with unpaired electrons, play a large role in most reactions of alkanes, such as cracking and reformation where long-chain alkanes are converted into shorter-chain alkanes and straight-chain alkanes into branched-chain isomers.
In highly branched alkanes, the bond angle may differ significantly from the optimal value (109.5°) in order to allow the different groups sufficient space. This causes a tension in the molecule, known as steric hindrance, and can substantially increase the reactivity.
## Reactions with oxygen
All alkanes react with oxygen in a combustion reaction, although they become increasingly difficult to ignite as the number of carbon atoms increases. The general equation for complete combustion is:
In the absence of sufficient oxygen, carbon monoxide or even soot can be formed, as shown below:
for example methane:
See the alkane heat of formation table for detailed data.
The standard enthalpy change of combustion, ΔcHo, for alkanes increases by about 650 kJ/mol per CH2 group. Branched-chain alkanes have lower values of ΔcHo than straight-chain alkanes of the same number of carbon atoms, and so can be seen to be somewhat more stable.
## Reactions with halogens
Alkanes react with halogens in a so-called free radical halogenation reaction. The hydrogen atoms of the alkane are progressively replaced by halogen atoms. Free radicals are the reactive species which participate in the reaction, which usually leads to a mixture of products. The reaction is highly exothermic, and can lead to an explosion.
These reactions are an important industrial route to halogenated hydrocarbons. There are three steps:
- Initiation the halogen radicals form by homolysis. Usually, energy in the form of heat or light is required.
- Chain reaction then takes place — the halogen radical abstracts a hydrogen from the alkane to give an alkyl radical. This reacts further.
- 'Chain termination where step the radicals recombine.
Experiments have shown that all halogenation produces a mixture of all possible isomers, indicating that all hydrogen atoms are susceptible to reaction. The mixture produced, however, is not a statistical mixture: secondary and tertiary hydrogen atoms are preferentially replaced due to the greater stability of secondary and tertiary free radicals. An example can be seen in the monobromination of propane:[7]
## Cracking
Cracking breaks larger molecules into smaller ones. This can be done with a thermal or catalytic method. The thermal cracking process follows a homolytic mechanism, that is, bonds break symmetrically and thus pairs of free radicals are formed. The catalytic cracking process involves the presence of acid catalysts (usually solid acids such as silica-alumina and zeolites) which promote a heterolytic (asymmetric) breakage of bonds yielding pairs of ions of opposite charges, usually a carbocation and the very unstable hydride anion. Carbon-localized free radicals and cations are both highly unstable and undergo processes of chain rearrangement, C-C scission in position beta (i.e., cracking) and intra- and intermolecular hydrogen transfer or hydride transfer. In both types of processes, the corresponding reactive intermediates (radicals, ions) are permanently regenerated, and thus they proceed by a
self-propagating chain mechanism. The chain of reactions is eventually terminated by radical or ion recombination.
Here is an example of cracking with butane CH3-CH2-CH2-CH3
- 1st possibility (48%): breaking is done on the CH3-CH2 bond.
CH3* / *CH2-CH2-CH3
after a certain number of steps, we will obtain an alkane and an alkene:
CH4 + CH2=CH-CH3
- 2nd possibility (38%): breaking is done on the CH2-CH2 bond.
CH3-CH2* / *CH2-CH3
after a certain number of steps, we will obtain an alkane and an alkene
from different types: CH3-CH3 + CH2=CH2
- 3rd possibility (14%): breaking of a C-H bond
after a certain number of steps, we will obtain an alkene and hydrogen gas: CH2=CH-CH2-CH3 + H2
## Isomerization and reformation
Isomerization and reformation are processes in which straight-chain alkanes are heated in the presence of a platinum catalyst. In isomerization, the alkanes become branched-chain isomers. In reformation, the alkanes become cycloalkanes or aromatic hydrocarbons, giving off hydrogen as a by-product. Both of these processes raise the octane number of the substance.
## Other reactions
Alkanes will react with steam in the presence of a nickel catalyst to give hydrogen. Alkanes can by chlorosulfonated and nitrated, although both reactions require special conditions. The fermentation of alkanes to carboxylic acids is of some technical importance. In the Reed reaction, sulfur dioxide, chlorine and light convert hydrocarbons to sulfonyl chlorides.
# Hazards
Methane is explosive when mixed with air (1 – 8% CH4) and is a strong greenhouse gas: other lower alkanes can also form explosive mixtures with air. The lighter liquid alkanes are highly flammable, although this risk decreases with the length of the carbon chain. Pentane, hexane, heptane and octane are classed as dangerous for the environment and harmful. The straight chain isomer of hexane is a neurotoxin, and therefore rarely used commercially. | https://www.wikidoc.org/index.php/Alkane | |
f0319d13b35ff5cd5b950d162021e15d6bb0bd7f | wikidoc | Allele | Allele
An allele (Template:PronEng (US), Template:IPA) is a viable DNA (deoxyribonucleic acid) coding that occupies a given locus (position) on a chromosome. Usually alleles are sequences that code for a gene, but sometimes the term is used to refer to a non-gene sequence. An individual's genotype for that gene is the set of alleles it happens to possess. In a diploid organism, one that has two copies of each chromosome, two alleles make up the individual's genotype. The word came from Greek αλληλος = "each other".
An example is the gene for blossom colour in many species of flower — a single gene controls the colour of the petals, but there may be several different versions (or alleles) of the gene. One version might result in red petals, while another might result in white petals. The resulting colour of an individual flower will depend on which two alleles it possesses for the gene and how the two interact.
# Introduction
An allele is an alternative form of a gene (in diploids, one member of a pair) that is located at a specific position on a specific chromosome.
Diploid organisms, for example, humans, have paired homologous chromosomes in their somatic cells, and these contain two copies of each gene. An organism in which the two copies of the gene are identical — that is, have the same allele — is called homozygous for that gene. An organism which has two different alleles of the gene is called heterozygous. Phenotypes (the expressed characteristics) associated with a certain allele can sometimes be dominant or recessive, but often they are neither. A dominant phenotype will be expressed when at least one allele of its associated type is present, whereas a recessive phenotype will only be expressed when both alleles are of its associated type.
However, there are exceptions to the way heterozygotes express themselves in the phenotype. One exception is incomplete dominance (sometimes called blending inheritance) when alleles blend their traits in the phenotype. An example of this would be seen if, when crossing Antirrhinums — flowers with incompletely dominant "red" and "white" alleles for petal color — the resulting offspring had pink petals. Another exception is co-dominance, where both alleles are active and both traits are expressed at the same time; for example, both red and white petals in the same bloom or red and white flowers on the same plant. Codominance is also apparent in human blood types. A person with one "A" blood type allele and one "B" blood type allele would have a blood type of "AB".
A wild type allele is an allele which is considered to be "normal" for the organism in question, as opposed to a mutant allele which is usually a relatively new modification.
(Note that with the advent of neutral genetic markers, the term 'allele' is now often used to refer to DNA sequence variants in non-functional, or junk DNA. For example, allele frequency tables are often presented for genetic markers, such as the DYS markers.) Also there are many different types of alleles.
# Equations
There are two equations for the frequency of two alleles of a given gene (see Hardy-Weinberg principle).
Equation 1: p+q=1,
Equation 2: p^2+2pq+q^2=1
where p is the frequency of one allele and q is the frequency of the other allele. Under appropriate conditions, subject to numerous limitations regarding the applicability of the Hardy-Weinberg principle, p^2 is the population fraction that is homozygous for the p allele, 2pq is the frequency of heterozygotes and q^2 is the population fraction that is homozygous for the q allele.
Natural selection can act on p and q in Equation 1, and obviously affect the frequency of alleles seen in Equation 2.
Equation 2 is a consequence of Equation 1, obtained by squaring both sides and applying the binomial theorem to the left-hand side.
Conversely, p^2+2pq+q^2=1 implies p+q=1 since p and q are positive numbers.
The following equation (commonly termed the Lee equation) can be used to calculate the number of possible genotypes in a diploid organism for a specific gene with a given number of alleles.
G=(a^2+a)/2
where a is the number of different alleles for the gene being dealt with and G is the number of possible genotypes.
For example, the human ABO blood group gene has three alleles; A (for blood group A), B (for blood group B) and i (for blood group O). As such, (using the equation) the number of possible genotypes a human may have with respect to the ABO gene are 6 (AA, Ai, AB, BB, Bi, ii). The equation does not specify the number of possible phenotypes, however. Such an equation would be quite impossible as the number of possible phenotypes varies amongst different genes and their alleles. For example, in a diploid heterozygote some genotypes may show complete dominance, incomplete dominance etc., depending of the gene involved.
# Types
There are 4 different types of alleles. Dominant, recessive, codominant, and incomplete dominant. Depending on the inheritance of two alleles, a person may therefore end up having a dominant, recessive, codominant, or incomplete dominant trait. In a single-gene trait, only two alleles determine the trait. In a polygenic trait, more than two alleles control the trait.
An example of a dominant and a recessive trait is the (dis)possession of a widow's peak. Those who have a widow's peak are dominant and those who do not have one are recessive.
An example of a codominant trait occurs in certain types of calves (cow's young). Some calves are known as "blue roans" for their appearance of both blue and grey hairs.
An example of an incomplete dominant trait occurs in a pink 4-o'clock flower. When a red flower (dominant) and a white flower (recessive) are crossed , those flowers with a heterozygous genotype for color are pink, showing the incomplete dominance of the red allele.
An example of multiple alleles is blood type. There are three alleles for blood type, A, B, and O. Because of this, people can have blood type A, B, AB, or O. AA or AO results in type A, BB or BO in type B, AB results in AB, and OO results in type O.
# Genetic Disorders
Genetic disorders are normally caused by the acquisition of two recessive alleles for a single-gene trait. Genetic disorders such as these include Albinism, Cystic Fibrosis, Galactosemia, Phenylketonuria (PKU), and Tay-Sachs Disease. In these cases the two alleles are autosomal (not sex chromosomes). Other disorders are recessive, but because they are located on the X chromosomes (of which men have only one copy), they are much more frequent in men than in women. One example of such a disorder is the Fragile X syndrome.
Some other disorders, such as Huntington's disease, are caused by the presence of a dominant allele. | Allele
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
An allele (Template:PronEng (US), Template:IPA) is a viable DNA (deoxyribonucleic acid) coding that occupies a given locus (position) on a chromosome. Usually alleles are sequences that code for a gene, but sometimes the term is used to refer to a non-gene sequence. An individual's genotype for that gene is the set of alleles it happens to possess. In a diploid organism, one that has two copies of each chromosome, two alleles make up the individual's genotype. The word came from Greek αλληλος = "each other".
An example is the gene for blossom colour in many species of flower — a single gene controls the colour of the petals, but there may be several different versions (or alleles) of the gene. One version might result in red petals, while another might result in white petals. The resulting colour of an individual flower will depend on which two alleles it possesses for the gene and how the two interact.
# Introduction
An allele is an alternative form of a gene (in diploids, one member of a pair) that is located at a specific position on a specific chromosome.
Diploid organisms, for example, humans, have paired homologous chromosomes in their somatic cells, and these contain two copies of each gene. An organism in which the two copies of the gene are identical — that is, have the same allele — is called homozygous for that gene. An organism which has two different alleles of the gene is called heterozygous. Phenotypes (the expressed characteristics) associated with a certain allele can sometimes be dominant or recessive, but often they are neither. A dominant phenotype will be expressed when at least one allele of its associated type is present, whereas a recessive phenotype will only be expressed when both alleles are of its associated type.
However, there are exceptions to the way heterozygotes express themselves in the phenotype. One exception is incomplete dominance (sometimes called blending inheritance) when alleles blend their traits in the phenotype. An example of this would be seen if, when crossing Antirrhinums — flowers with incompletely dominant "red" and "white" alleles for petal color — the resulting offspring had pink petals. Another exception is co-dominance, where both alleles are active and both traits are expressed at the same time; for example, both red and white petals in the same bloom or red and white flowers on the same plant. Codominance is also apparent in human blood types. A person with one "A" blood type allele and one "B" blood type allele would have a blood type of "AB".
A wild type allele is an allele which is considered to be "normal" for the organism in question, as opposed to a mutant allele which is usually a relatively new modification.
(Note that with the advent of neutral genetic markers, the term 'allele' is now often used to refer to DNA sequence variants in non-functional, or junk DNA. For example, allele frequency tables are often presented for genetic markers, such as the DYS markers.) Also there are many different types of alleles.
# Equations
There are two equations for the frequency of two alleles of a given gene (see Hardy-Weinberg principle).
Equation 1: <math>p+q=1</math>,
Equation 2: <math>p^2+2pq+q^2=1</math>
where <math>p</math> is the frequency of one allele and <math>q</math> is the frequency of the other allele. Under appropriate conditions, subject to numerous limitations regarding the applicability of the Hardy-Weinberg principle, <math>p^2</math> is the population fraction that is homozygous for the <math>p</math> allele, <math>2pq</math> is the frequency of heterozygotes and <math>q^2</math> is the population fraction that is homozygous for the <math>q</math> allele.
Natural selection can act on <math>p</math> and <math>q</math> in Equation 1, and obviously affect the frequency of alleles seen in Equation 2.
Equation 2 is a consequence of Equation 1, obtained by squaring both sides and applying the binomial theorem to the left-hand side.
Conversely, <math>p^2+2pq+q^2=1</math> implies <math>p+q=1</math> since <math>p</math> and <math>q</math> are positive numbers.
The following equation (commonly termed the Lee equation) can be used to calculate the number of possible genotypes in a diploid organism for a specific gene with a given number of alleles.
<math>G=(a^2+a)/2</math>
where <math>a</math> is the number of different alleles for the gene being dealt with and <math>G</math> is the number of possible genotypes.
For example, the human ABO blood group gene has three alleles; A (for blood group A), B (for blood group B) and i (for blood group O). As such, (using the equation) the number of possible genotypes a human may have with respect to the ABO gene are 6 (AA, Ai, AB, BB, Bi, ii). The equation does not specify the number of possible phenotypes, however. Such an equation would be quite impossible as the number of possible phenotypes varies amongst different genes and their alleles. For example, in a diploid heterozygote some genotypes may show complete dominance, incomplete dominance etc., depending of the gene involved.
# Types
There are 4 different types of alleles. Dominant, recessive, codominant, and incomplete dominant. Depending on the inheritance of two alleles, a person may therefore end up having a dominant, recessive, codominant, or incomplete dominant trait. In a single-gene trait, only two alleles determine the trait. In a polygenic trait, more than two alleles control the trait.
An example of a dominant and a recessive trait is the (dis)possession of a widow's peak. Those who have a widow's peak are dominant and those who do not have one are recessive.
An example of a codominant trait occurs in certain types of calves (cow's young). Some calves are known as "blue roans" for their appearance of both blue and grey hairs.
An example of an incomplete dominant trait occurs in a pink 4-o'clock flower. When a red flower (dominant) and a white flower (recessive) are crossed , those flowers with a heterozygous genotype for color are pink, showing the incomplete dominance of the red allele.
An example of multiple alleles is blood type. There are three alleles for blood type, A, B, and O. Because of this, people can have blood type A, B, AB, or O. AA or AO results in type A, BB or BO in type B, AB results in AB, and OO results in type O.
# Genetic Disorders
Genetic disorders are normally caused by the acquisition of two recessive alleles for a single-gene trait. Genetic disorders such as these include Albinism, Cystic Fibrosis, Galactosemia, Phenylketonuria (PKU), and Tay-Sachs Disease. In these cases the two alleles are autosomal (not sex chromosomes). Other disorders are recessive, but because they are located on the X chromosomes (of which men have only one copy), they are much more frequent in men than in women. One example of such a disorder is the Fragile X syndrome.
Some other disorders, such as Huntington's disease, are caused by the presence of a dominant allele. | https://www.wikidoc.org/index.php/Allele | |
071e0e30d13db2f7b6acee7fb16c9010b3330e3f | wikidoc | Almond | Almond
The Almond (Prunus dulcis, syn. Prunus amygdalus Batsch., Amygdalus communis L., Amygdalus dulcis Mill.) is a species of Prunus belonging to the subfamily Prunoideae of the family Rosaceae; within Prunus, it is classified with the Peach in the subgenus Amygdalus, distinguished from the other subgenera by the corrugated seed shell. An almond is also the seed of this tree.
# Description
It is native to southwest Asia, from northwestern Saudi Arabia, north through western Jordan, Israel, Lebanon, western Syria, to southern Turkey. It is a small deciduous tree, growing to 4–10 m tall, with a trunk up to 30 cm diameter. The young shoots are green at first, becoming purplish where exposed to sunlight, then grey in their second year. The leaves are lanceolate, 4–13 cm long and 1.2–4 cm broad, with a serrated margin and a 2.5 cm petiole. The flowers are white or pale pink, 3–5 cm diameter with five petals, produced singly or in pairs before the leaves in early spring.
The fruit is a drupe 3.5–6 cm long, with a downy outer coat. The outer covering or exocarp, fleshy in other members of Prunus such as the plum and cherry, is reduced to a leathery grey-green coat called the hull, which contains inside a hard shell the edible kernel, commonly called a nut in culinary terms. Generally, one kernel is present, but occasionally two. However, in botanical terms, an almond is not a true nut. In botanical parlance, the reticulated hard stony shell is called an endocarp. It is mature in the autumn, 7–8 months after flowering.
# Origin and history
The wild form of domesticated almond grows in parts of the Levant; almonds must first have been taken into cultivation in this region. The fruit of the wild forms contains the glycoside amygdalin, "which becomes transformed into deadly prussic acid (hydrogen cyanide) after crushing, chewing, or any other injury to the seed". Before cultivation and domestication occurred, wild almonds were harvested as food and doubtless were processed by leaching or roasting to remove their toxicity. The domesticated form can ripen fruit as far north as the British Isles.
However, domesticated almonds are not toxic; Jared Diamond argues that a common genetic mutation causes an absence of glycoside amygdalin, and this mutant was grown by early farmers, "at first unintentionally in the garbage heaps and later intentionally in their orchards". Zohary and Hopf believe that almonds were one of the earliest domesticated fruit-trees due to "the ability of the grower to raise attractive almonds from seed. Thus in spite of the fact that this plant does not lend itself to propagation from suckers or from cuttings, it could have been domesticated even before the introduction of grafting". Domesticated almonds appear in the Early Bronze Age (3000–2000 BC) of the Near East, or possibly a little earlier. A well-known archaeological example of almond is the fruits found in Tutankhamun's tomb in Egypt (c. 1325 BC), probably imported from the Levant.
Almond is called Lawz in Arabic, Baadaam in Persian , Urdu and Hindi.
# Production
Global production of almonds is around 1.5 million tonnes, with a low of 1 million tonnes in 1995 and a peak of 1.85 million tonnes in 2002 according to Food and Agriculture Organization (FAO) figures (pdf file). Major producers include Greece, Iran, Italy, Morocco, Portugal, Spain, Syria, Turkey, and the world's largest producer, the United States. In Turkey, most of the production comes from the Datca peninsula. In Spain, numerous commercial cultivars of sweet almond are produced, most notably the Jordan almond (imported from Málaga) and the Valencia almond. In the United States, production is concentrated in California, with almonds being California's sixth leading agricultural product and its top agricultural export. California exported almonds valued at 1.08 billion dollars in 2003, about 70% of total California almond crop.
Because of cases of Salmonella traced to almonds in 2001 and 2004, in 2006 the California Almond Board proposed and the USDA approved rules regarding the nature of almonds available to the public. From 1 September 2007, raw almonds will technically no longer be available in the United States. Controversially, almonds labeled as "raw" will required to be steam pasteurised or chemically treated with propylene oxide.
# Diseases
# Pollination
The pollination of California's almonds is the largest annual managed pollination event in the world, with close to one million hives (nearly half of all beehives in the USA) being trucked in February to the almond groves. Much of the pollination is managed by pollination brokers, who contract with migratory beekeepers from at least 38 states for the event.
# Sweet and bitter almonds
There are two forms of the plant, one (often with white flowers) producing sweet almonds, and the other (often with pink flowers) producing bitter almonds. The kernel of the former contains a fixed oil and emulsion. As late as the early 20th century the oil was used internally in medicine, with the stipulation that it must not be adulterated with that of the bitter almond; it remains fairly popular in alternative medicine, particularly as a carrier oil in aromatherapy, but has fallen out of prescription among doctors.
The bitter almond is rather broader and shorter than the sweet almond, and contains about 50% of the fixed oil which also occurs in sweet almonds. It also contains the enzyme emulsin which, in the presence of water, acts on a soluble glucoside, amygdalin, yielding glucose, cyanide and the essential oil of bitter almonds or benzaldehyde. Bitter almonds may yield from 6 to 8% of hydrogen cyanide. Extract of bitter almond was once used medicinally but even in small doses effects are severe and in larger doses can be deadly; the cyanide must be removed before consumption.
The nut has also been used as a preventative for alcohol intoxication. Folklore claims that almonds are poisonous for foxes.
# Culinary uses
While the almond is most often eaten on its own, raw or toasted, it is used in some dishes. It, along with other nuts, is often sprinkled over desserts, particularly sundaes and other ice cream based dishes. It is also used in making baklava and nougat. There is also almond butter, a spread similar to peanut butter, popular with peanut allergy sufferers and for its less salty taste. The young, developing fruit of the almond tree can also be eaten as a whole ("green almonds"), when it is still green and fleshy on the outside, and the inner shell has not yet hardened. The fruit is somewhat sour, and is available only from mid April to mid June; pickling or brining extends the fruit's shelf life.
The sweet almond itself contains practically no carbohydrates and may therefore be made into flour for cakes and biscuits for low carbohydrate diets or for patients suffering from diabetes mellitus or any other form of glycosuria.
A standard serving of almond flour, 1 cup, contains 20 grammes of carbohydrates, of which 10 g is dietary fibre, for a net of 10 g of carbohydrate per cup. This makes almond flour very desirable for use in cake and bread recipes by people on carbohydrate-restricted diets.
In Greece, ground blanched almonds are used as the base material in a great variety of desserts, usually called amygdalota (αμυγδαλωτά). Because of their white colour, most are traditionally considered "wedding sweets" and are served at wedding banquets.
Almonds can be processed into a milk substitute simply called almond milk; the nut's soft texture, mild flavour, and light colouring (when skinned) make for an efficient analog to dairy, and a soy-free choice, for lactose intolerant people, vegans, and so on. Raw, blanched, and lightly toasted almonds all work well for different production techniques, some of which are very similar to that of soymilk and some of which actually use no heat, resulting in "raw milk" (see raw foodism).
Sweet almonds are used in marzipan, nougat, and macaroons, as well as other desserts. Almonds are a rich source of Vitamin E, containing 24 mg per 100 g. They are also rich in monounsaturated fat, one of the two "good" fats responsible for lowering LDL cholesterol.
The Marcona variety of almond, which is shorter, rounder, sweeter, and more delicate in texture than other varieties, originated in Spain and is becoming popular in North America and other parts of the world. Marcona almonds are traditionally served after being lightly fried in oil, and are also used by Spanish chefs to prepare a dessert called turrón.
In China, almonds are used in a popular dessert when they are mixed with milk and then served hot. In Indian cuisine, almonds are the base ingredient for pasanda-style curries.
## Almond oil
"Oleum Amygdalae", the fixed oil, is prepared from either variety of almond and is a glyceryl oleate, with a slight odour and a nutty taste. It is almost insoluble in alcohol but readily soluble in chloroform or ether. It may be used as a substitute for olive oil.
The sweet almond oil is obtained from the dried kernel of the plant. This oil has been traditionally used by massage therapists to lubricate the skin during a massage session, being considered by many to be an effective emollient.
## Almond syrup
Historically, almond syrup was an emulsion of sweet and bitter almonds usually made with barley syrup (orgeat syrup) or in a syrup of orange-flower water and sugar.
Grocer's Encyclopedia notes that "Ten parts of sweet almonds are generally employed to three parts of bitter almonds", however due to the cyanide found in bitter almonds, modern syrups generally consist of only sweet almonds.Template:Grocers
## Possible health benefits
Edgar Cayce, a man regarded as the father of American holistic medicine, also highly favoured the almond. In his readings, Cayce often recommended that almonds be included in the diet. Claimed health benefits include improved complexion, improved movement of food through the colon and the prevention of cancer.
Recent research associates inclusion of almonds in the diet with elevating the blood levels of high density lipoproteins and of lowering the levels of low density lipoproteins.
In Ayurveda, the Indian System of Medicine, almond is considered a nutritive for brain and nervous system. It is said to induce high intellectual level and longevity. Almond oil is called Roghan Badam in both Ayurveda and Unani Tibb (the Greco-Persian System of Medicine). It is extracted by cold process and is considered a nutritive aphrodisiac both for massage and internal consumption. Recent studies have shown that the constituents of almond have anti-inflammatory, immunity boosting, and anti-hepatotoxicity effects.
# Cultural aspects
The almond is highly revered in some cultures.
The tree grows in Syria and Israel, and is mentioned numerous times in the Bible. The Hebrew name, "shaked", means industrious or vigilant, which is appropriate, as the almond is one of the first trees to flower in Israel, usually in early February, coinciding with Tu Bishvat, the Jewish arbor day.
In ancient Israel, the almond was a symbol of watchfulness and promise due to its early flowering, symbolizing God's sudden and rapid punishment of His people; in Jeremiah 1:11-12, for instance. In the Bible the almond is mentioned ten times, beginning with Genesis 43:11, where it is described as "among the best of fruits". In Numbers 17 Levi is chosen from the other tribes of Israel by Aaron's rod, which brought forth almond flowers. According to tradition, the rod of Aaron bore sweet almonds on one side and bitter on the other; if the Israelites followed the Lord, the sweet almonds would be ripe and edible, but if they were to forsake the path of the Lord, the bitter almonds would predominate. The almond blossom supplied a model for the menorah which stood in the Holy Temple, "Three cups, shaped like almond blossoms, were on one branch, with a knob and a flower; and three cups, shaped like almond blossoms, were on the other...on the candlestick itself were four cups, shaped like almond blossoms, with its knobs and flowers" (Exodus 25:33-34; 37:19-20). Similarly, Christian symbolism often uses almond branches as a symbol of the Virgin Birth of Jesus; paintings often include almonds encircling the baby Jesus and as a symbol of Mary.
The word "Luz", which appears in Genesis 30:37, is usually translated as "hazel", but some believe it is another name for the almond (Luz in Arabic means Almonds). In India, consumption of almonds is believed to be good for the brain, while the Chinese consider it a symbol of enduring sadness and female beauty.
# Etymology
The word 'almond' comes from Old French almande or alemande, late Latin amandola, derived through a form amingdola from the Greek αμυγδαλη (cf Amygdala), an almond. The al- for a- may be due to a confusion with the Arabic article al, the word having first dropped the a- as in the Italian form mandorla; the British pronunciation ar-mond and the modern Catalan ametlla and modern French amande show the true form of the word. | Almond
Template:Nutritionalvalue
The Almond (Prunus dulcis, syn. Prunus amygdalus Batsch., Amygdalus communis L., Amygdalus dulcis Mill.) is a species of Prunus belonging to the subfamily Prunoideae of the family Rosaceae; within Prunus, it is classified with the Peach in the subgenus Amygdalus, distinguished from the other subgenera by the corrugated seed shell. An almond is also the seed of this tree.
# Description
It is native to southwest Asia, from northwestern Saudi Arabia, north through western Jordan, Israel, Lebanon, western Syria, to southern Turkey.[1] It is a small deciduous tree, growing to 4–10 m tall, with a trunk up to 30 cm diameter. The young shoots are green at first, becoming purplish where exposed to sunlight, then grey in their second year. The leaves are lanceolate, 4–13 cm long and 1.2–4 cm broad, with a serrated margin and a 2.5 cm petiole. The flowers are white or pale pink, 3–5 cm diameter with five petals, produced singly or in pairs before the leaves in early spring.[2][3]
The fruit is a drupe 3.5–6 cm long, with a downy outer coat. The outer covering or exocarp, fleshy in other members of Prunus such as the plum and cherry, is reduced to a leathery grey-green coat called the hull, which contains inside a hard shell the edible kernel, commonly called a nut in culinary terms. Generally, one kernel is present, but occasionally two. However, in botanical terms, an almond is not a true nut. In botanical parlance, the reticulated hard stony shell is called an endocarp. It is mature in the autumn, 7–8 months after flowering.[2][3]
# Origin and history
The wild form of domesticated almond grows in parts of the Levant; almonds must first have been taken into cultivation in this region. The fruit of the wild forms contains the glycoside amygdalin, "which becomes transformed into deadly prussic acid (hydrogen cyanide) after crushing, chewing, or any other injury to the seed".[4] Before cultivation and domestication occurred, wild almonds were harvested as food and doubtless were processed by leaching or roasting to remove their toxicity. The domesticated form can ripen fruit as far north as the British Isles.
However, domesticated almonds are not toxic; Jared Diamond argues that a common genetic mutation causes an absence of glycoside amygdalin, and this mutant was grown by early farmers, "at first unintentionally in the garbage heaps and later intentionally in their orchards".[5] Zohary and Hopf believe that almonds were one of the earliest domesticated fruit-trees due to "the ability of the grower to raise attractive almonds from seed. Thus in spite of the fact that this plant does not lend itself to propagation from suckers or from cuttings, it could have been domesticated even before the introduction of grafting".[4] Domesticated almonds appear in the Early Bronze Age (3000–2000 BC) of the Near East, or possibly a little earlier. A well-known archaeological example of almond is the fruits found in Tutankhamun's tomb in Egypt (c. 1325 BC), probably imported from the Levant.[4]
Almond is called Lawz in Arabic, Baadaam in Persian , Urdu and Hindi.
# Production
Global production of almonds is around 1.5 million tonnes, with a low of 1 million tonnes in 1995 and a peak of 1.85 million tonnes in 2002 according to Food and Agriculture Organization (FAO) figures (pdf file). Major producers include Greece, Iran, Italy, Morocco, Portugal, Spain, Syria, Turkey, and the world's largest producer, the United States. In Turkey, most of the production comes from the Datca peninsula. In Spain, numerous commercial cultivars of sweet almond are produced, most notably the Jordan almond (imported from Málaga) and the Valencia almond. In the United States, production is concentrated in California, with almonds being California's sixth leading agricultural product and its top agricultural export. California exported almonds valued at 1.08 billion dollars in 2003, about 70% of total California almond crop.
Because of cases of Salmonella traced to almonds in 2001 and 2004, in 2006 the California Almond Board proposed and the USDA approved rules regarding the nature of almonds available to the public. From 1 September 2007, raw almonds will technically no longer be available in the United States. Controversially, almonds labeled as "raw" will required to be steam pasteurised or chemically treated with propylene oxide.[6]
# Diseases
# Pollination
The pollination of California's almonds is the largest annual managed pollination event in the world, with close to one million hives (nearly half of all beehives in the USA) being trucked in February to the almond groves. Much of the pollination is managed by pollination brokers, who contract with migratory beekeepers from at least 38 states for the event.
# Sweet and bitter almonds
There are two forms of the plant, one (often with white flowers) producing sweet almonds, and the other (often with pink flowers) producing bitter almonds. The kernel of the former contains a fixed oil and emulsion. As late as the early 20th century the oil was used internally in medicine, with the stipulation that it must not be adulterated with that of the bitter almond; it remains fairly popular in alternative medicine, particularly as a carrier oil in aromatherapy, but has fallen out of prescription among doctors.
The bitter almond is rather broader and shorter than the sweet almond, and contains about 50% of the fixed oil which also occurs in sweet almonds. It also contains the enzyme emulsin which, in the presence of water, acts on a soluble glucoside, amygdalin, yielding glucose, cyanide and the essential oil of bitter almonds or benzaldehyde. Bitter almonds may yield from 6 to 8% of hydrogen cyanide. Extract of bitter almond was once used medicinally but even in small doses effects are severe and in larger doses can be deadly; the cyanide must be removed before consumption.[7]
The nut has also been used as a preventative for alcohol intoxication. Folklore claims that almonds are poisonous for foxes[citation needed].
# Culinary uses
While the almond is most often eaten on its own, raw or toasted, it is used in some dishes. It, along with other nuts, is often sprinkled over desserts, particularly sundaes and other ice cream based dishes. It is also used in making baklava and nougat. There is also almond butter, a spread similar to peanut butter, popular with peanut allergy sufferers and for its less salty taste. The young, developing fruit of the almond tree can also be eaten as a whole ("green almonds"), when it is still green and fleshy on the outside, and the inner shell has not yet hardened. The fruit is somewhat sour, and is available only from mid April to mid June; pickling or brining extends the fruit's shelf life.
The sweet almond itself contains practically no carbohydrates and may therefore be made into flour for cakes and biscuits for low carbohydrate diets or for patients suffering from diabetes mellitus or any other form of glycosuria.
A standard serving of almond flour, 1 cup, contains 20 grammes of carbohydrates, of which 10 g is dietary fibre, for a net of 10 g of carbohydrate per cup. This makes almond flour very desirable for use in cake and bread recipes by people on carbohydrate-restricted diets.
In Greece, ground blanched almonds are used as the base material in a great variety of desserts, usually called amygdalota (αμυγδαλωτά). Because of their white colour, most are traditionally considered "wedding sweets" and are served at wedding banquets.
Almonds can be processed into a milk substitute simply called almond milk; the nut's soft texture, mild flavour, and light colouring (when skinned) make for an efficient analog to dairy, and a soy-free choice, for lactose intolerant people, vegans, and so on. Raw, blanched, and lightly toasted almonds all work well for different production techniques, some of which are very similar to that of soymilk and some of which actually use no heat, resulting in "raw milk" (see raw foodism).
Sweet almonds are used in marzipan, nougat, and macaroons, as well as other desserts. Almonds are a rich source of Vitamin E, containing 24 mg per 100 g.[8] They are also rich in monounsaturated fat, one of the two "good" fats responsible for lowering LDL cholesterol.
The Marcona variety of almond, which is shorter, rounder, sweeter, and more delicate in texture than other varieties, originated in Spain and is becoming popular in North America and other parts of the world.[9] Marcona almonds are traditionally served after being lightly fried in oil, and are also used by Spanish chefs to prepare a dessert called turrón.
In China, almonds are used in a popular dessert when they are mixed with milk and then served hot. In Indian cuisine, almonds are the base ingredient for pasanda-style curries.
## Almond oil
"Oleum Amygdalae", the fixed oil, is prepared from either variety of almond and is a glyceryl oleate, with a slight odour and a nutty taste. It is almost insoluble in alcohol but readily soluble in chloroform or ether. It may be used as a substitute for olive oil.
The sweet almond oil is obtained from the dried kernel of the plant. This oil has been traditionally used by massage therapists to lubricate the skin during a massage session, being considered by many to be an effective emollient.
## Almond syrup
Historically, almond syrup was an emulsion of sweet and bitter almonds usually made with barley syrup (orgeat syrup) or in a syrup of orange-flower water and sugar.
Grocer's Encyclopedia notes that "Ten parts of sweet almonds are generally employed to three parts of bitter almonds", however due to the cyanide found in bitter almonds, modern syrups generally consist of only sweet almonds.Template:Grocers
## Possible health benefits
Edgar Cayce, a man regarded as the father of American holistic medicine, also highly favoured the almond. In his readings, Cayce often recommended that almonds be included in the diet. Claimed health benefits include improved complexion, improved movement of food through the colon and the prevention of cancer.
[10] Recent research associates inclusion of almonds in the diet with elevating the blood levels of high density lipoproteins and of lowering the levels of low density lipoproteins.[11][12]
In Ayurveda, the Indian System of Medicine, almond is considered a nutritive for brain and nervous system. It is said to induce high intellectual level and longevity. Almond oil is called Roghan Badam in both Ayurveda and Unani Tibb (the Greco-Persian System of Medicine). It is extracted by cold process and is considered a nutritive aphrodisiac both for massage and internal consumption. Recent studies have shown that the constituents of almond have anti-inflammatory, immunity boosting, and anti-hepatotoxicity effects.[13]
# Cultural aspects
The almond is highly revered in some cultures.
The tree grows in Syria and Israel, and is mentioned numerous times in the Bible. The Hebrew name, "shaked", means industrious or vigilant, which is appropriate, as the almond is one of the first trees to flower in Israel, usually in early February, coinciding with Tu Bishvat, the Jewish arbor day.
In ancient Israel, the almond was a symbol of watchfulness and promise due to its early flowering, symbolizing God's sudden and rapid punishment of His people; in Jeremiah 1:11-12, for instance. In the Bible the almond is mentioned ten times, beginning with Genesis 43:11, where it is described as "among the best of fruits". In Numbers 17 Levi is chosen from the other tribes of Israel by Aaron's rod, which brought forth almond flowers. According to tradition, the rod of Aaron bore sweet almonds on one side and bitter on the other; if the Israelites followed the Lord, the sweet almonds would be ripe and edible, but if they were to forsake the path of the Lord, the bitter almonds would predominate. The almond blossom supplied a model for the menorah which stood in the Holy Temple, "Three cups, shaped like almond blossoms, were on one branch, with a knob and a flower; and three cups, shaped like almond blossoms, were on the other...on the candlestick itself were four cups, shaped like almond blossoms, with its knobs and flowers" (Exodus 25:33-34; 37:19-20). Similarly, Christian symbolism often uses almond branches as a symbol of the Virgin Birth of Jesus; paintings often include almonds encircling the baby Jesus and as a symbol of Mary.
The word "Luz", which appears in Genesis 30:37, is usually translated as "hazel", but some believe it is another name for the almond (Luz in Arabic means Almonds). In India, consumption of almonds is believed to be good for the brain, while the Chinese consider it a symbol of enduring sadness and female beauty.
# Etymology
The word 'almond' comes from Old French almande or alemande, late Latin amandola, derived through a form amingdola from the Greek αμυγδαλη (cf Amygdala), an almond. The al- for a- may be due to a confusion with the Arabic article al, the word having first dropped the a- as in the Italian form mandorla; the British pronunciation ar-mond and the modern Catalan ametlla and modern French amande show the true form of the word. | https://www.wikidoc.org/index.php/Almond | |
0345ff1302abdf5b65ae942bb97fb366b26306e9 | wikidoc | Amnion | Amnion
# Overview
The amnion is a membranous sac which surrounds and protects the embryo. It is developed in reptiles, birds, and mammals, which are hence called “Amniota”; but not in amphibia and fish, which are consequently termed “Anamnia”. The primary function of this is the protection of the embryo for its future development into a fetus and eventually an animal.
# In humans
In the human embryo the earliest stages of the formation of the amnion have not been observed; in the youngest embryo which has been studied the amnion was already present as a closed sac, and appears in the inner cell-mass as a cavity. This cavity is roofed in by a single stratum of flattened, ectodermal cells, the amniotic ectoderm, and its floor consists of the prismatic ectoderm of the embryonic disk—the continuity between the roof and floor being established at the margin of the embryonic disk. Outside the amniotic ectoderm is a thin layer of mesoderm, which is continuous with that of the somatopleure and is connected by the body-stalk with the mesodermal lining of the chorion.
When first formed the amnion is in contact with the body of the embryo, but about the fourth or fifth week fluid (liquor amnii) begins to accumulate within it. This fluid increases in quantity and causes the amnion to expand and ultimately to adhere to the inner surface of the chorion, so that the extra-embryonic part of the coelom is obliterated. The liquor amnii increases in quantity up to the sixth or seventh month of pregnancy, after which it diminishes somewhat; at the end of pregnancy it amounts to about 1 liter. It allows of the free movements of the fetus during the later stages of pregnancy, and also protects it by diminishing the risk of injury from without. It contains less than two percent solids, consisting of urea and other extractives, inorganic salts, a small amount of protein, and frequently a trace of sugar. That some of the liquor amnii is swallowed by the fetus is proved by the fact that epidermal debris and hairs have been found among the contents of the fetal alimentary canal.
# In reptiles, birds, and many mammals
In reptiles, birds, and many mammals the amnion is developed in the following manner: At the point of constriction where the primitive digestive tube of the embryo joins the yolk-sac a reflection or folding upward of the somatopleure takes place. This, the amniotic fold, first makes its appearance at the cephalic extremity, and subsequently at the caudal end and sides of the embryo, and gradually rising more and more, its different parts meet and fuse over the dorsal aspect of the embryo, and enclose a cavity, the amniotic cavity. After the fusion of the edges of the amniotic fold, the two layers of the fold become completely separated, the inner forming the amnion, the outer the false amnion or serosa. The space between the amnion and the serosa constitutes the extra-embryonic celom, and for a time communicates with the embryonic celom.
# Additional images
- Section through the embryo.
- Human embryo of 2.6 mm.
- Diagram of a transverse section, showing the mode of formation of the amnion in the chick.
- Model of human embryo 1.3 mm. long.
- Sectional plan of the gravid uterus in the third and fourth month.
- Scheme of placental circulation.
- Human embryo of about fourteen days, with yolk-sac.
- Opened uterus with cat fetus in midgestation: 1 umbilicus, 2 amnion, 3 allantois, 4 Yolk sac, 5 developing marginal hematoma, 6 maternal part of placenta (endometrium) | Amnion
Template:Infobox Anatomy
# Overview
The amnion is a membranous sac which surrounds and protects the embryo. It is developed in reptiles, birds, and mammals, which are hence called “Amniota”; but not in amphibia and fish, which are consequently termed “Anamnia”. The primary function of this is the protection of the embryo for its future development into a fetus and eventually an animal.
# In humans
In the human embryo the earliest stages of the formation of the amnion have not been observed; in the youngest embryo which has been studied the amnion was already present as a closed sac, and appears in the inner cell-mass as a cavity. This cavity is roofed in by a single stratum of flattened, ectodermal cells, the amniotic ectoderm, and its floor consists of the prismatic ectoderm of the embryonic disk—the continuity between the roof and floor being established at the margin of the embryonic disk. Outside the amniotic ectoderm is a thin layer of mesoderm, which is continuous with that of the somatopleure and is connected by the body-stalk with the mesodermal lining of the chorion.
When first formed the amnion is in contact with the body of the embryo, but about the fourth or fifth week fluid (liquor amnii) begins to accumulate within it. This fluid increases in quantity and causes the amnion to expand and ultimately to adhere to the inner surface of the chorion, so that the extra-embryonic part of the coelom is obliterated. The liquor amnii increases in quantity up to the sixth or seventh month of pregnancy, after which it diminishes somewhat; at the end of pregnancy it amounts to about 1 liter. It allows of the free movements of the fetus during the later stages of pregnancy, and also protects it by diminishing the risk of injury from without. It contains less than two percent solids, consisting of urea and other extractives, inorganic salts, a small amount of protein, and frequently a trace of sugar. That some of the liquor amnii is swallowed by the fetus is proved by the fact that epidermal debris and hairs have been found among the contents of the fetal alimentary canal.
# In reptiles, birds, and many mammals
In reptiles, birds, and many mammals the amnion is developed in the following manner: At the point of constriction where the primitive digestive tube of the embryo joins the yolk-sac a reflection or folding upward of the somatopleure takes place. This, the amniotic fold, first makes its appearance at the cephalic extremity, and subsequently at the caudal end and sides of the embryo, and gradually rising more and more, its different parts meet and fuse over the dorsal aspect of the embryo, and enclose a cavity, the amniotic cavity. After the fusion of the edges of the amniotic fold, the two layers of the fold become completely separated, the inner forming the amnion, the outer the false amnion or serosa. The space between the amnion and the serosa constitutes the extra-embryonic celom, and for a time communicates with the embryonic celom.
# Additional images
- Section through the embryo.
- Human embryo of 2.6 mm.
- Diagram of a transverse section, showing the mode of formation of the amnion in the chick.
- Model of human embryo 1.3 mm. long.
- Sectional plan of the gravid uterus in the third and fourth month.
- Scheme of placental circulation.
- Human embryo of about fourteen days, with yolk-sac.
- Opened uterus with cat fetus in midgestation: 1 umbilicus, 2 amnion, 3 allantois, 4 Yolk sac, 5 developing marginal hematoma, 6 maternal part of placenta (endometrium) | https://www.wikidoc.org/index.php/Amnion | |
502958f1b3203fa8b25399718ec7086c34ee2f8d | wikidoc | Amoeba | Amoeba
Amoeba (sometimes amœba or ameba, plural amoebae) is a genus of protozoa that moves by means of temporary projections called pseudopods, and is well-known as a representative unicellular organism. The word amoeba or ameba is variously used to refer to it and its close relatives, now grouped as the Amoebozoa, or to all protozoa that move using pseudopods, otherwise termed amoeboids. The amoeba was first discovered by August Johann Rösel von Rosenhof in 1755.
# Habitat and study
Amoeba itself is found in decaying vegetation in fresh and salt water, wet soil, and animals. Due to the ease with which they may be obtained and kept alive they are common objects of study, both as representative protozoa and to demonstrate cell structure and function. The cells have several lobose pseudopods, with one large tubular pseudopod at the anterior and several secondary ones branching to the sides. The most famous species, Amoeba proteus, is 700-800 μm in length but amoebae vary from as large as a millimeter (Amoeba dubia which is visible to the naked eye) to far smaller than 700 μm. Its most recognizable features include a single nucleus and simple contractile vacuole to maintain osmotic pressure. The amoeba obtains its food through phagocytosis. Amoebas reproduce through binary fission.
Early naturalists referred to Amoeba as the Proteus animalcule after the Greek god Proteus who could change his shape. The name "amibe" was given to it by Bery St. Vincent, from the Greek amoibè, meaning change.
# Anatomy
An amoeba, from the order Amoebida, class Mastigophora phylum sarcodina protozoa, is a single-celled organism. They live in freshwater stagnant ponds, soil, streams, the ocean, and the bodies of other organisms. Some of the largest amoebae are about 1mm across, which means a human being would barely be able to see it with the naked eye. The word amoeba means “to change” in Greek (Encyclopedia of Science, 1).
An amoeba is composed of several different parts. One is a cell membrane, which is an amoeba’s outer covering. Then there is the nucleus, the central organelle, or brain, and the common animal cell organelles (Dery, 1). An amoeba also has endoplasm and ectoplasm, and the two specialized types of vacuoles (Dery, 1). See Figure 1 (Dery, 1).
The ectoplasm is the exterior gel of the amoeba and the endoplasm is the interior fluid. These two components are used for storing organelles and undergoing pseudopodial extension (see page seven, pseudopodial movement); locomotion of the amoeba and capturing food. See Figure 2. (Aardvark-Catalyst, 163-164).
The two vacuoles are the digestive and food vacuoles. The food vacuole is formed when the amoeba undertakes the process of phagocytosis (pseudopodia surrounding food ) (see Figure 3) (Aardvark-Catalyst, 163). Once the food vacuole is formed, it becomes a digestive vacuole, which is responsible for breaking down the food into energy (Encyclopedia of Science, 1). Also, an amoeba has a contractile vacuole, which is responsible for pumping water in and out of the amoeba.
Amoebae are diverse in many ways. For example, they drastically range in size from 1mm across (Blake, 1). Some traits even change in different environments, making it hard to tell the amoebae apart (Blake, 1). Also, some amoebae are carnivorous, some are herbivorous, and some are even omnivorous. Then, there are the parasitic ones (Blake, 1), which can live in one’s liver, lungs, brain- even heart (Innvista, 1)! These will become a cyst until they go inside of you, then they become a trophozite, their replicating forms (1).
# Stimuli
## Hypertonic and hypotonic solutions
Like most pies, amoebae are adversely affected by excessive osmotic pressure, like very salty or very fresh water. When an amoeba is put into salt water with enough concentration, some of its organelles, like the contractile vacuole, are damaged. As the amoeba prevents the salt from entering, instead the solution will pull water out of the amoeba, concentrating the salts inside. When this happens the amoeba will appear to shrink.
If a brine amoeba is put into fresh water and it is not a cyst at the time, its contractile vacuole will burst (Do, 1). This is because the vacuole’s job is to create a solution isotonic to the amoeba's environment. If the salt concentration inside the vacuole is too high, it will trigger water absorption. (Do, 1). Soon, the vacuole will burst before it has reached equilibrium. This means the amoeba will also burst. See Figure 4. (Do, 1).
Also, some enzymes might be damaged in the process, including digestive enzymes used in phagocytosis. (Gale, 1). The amoeba will ingest food but be unable to digest it to extract energy. The amoeba then will perish.
## Amoebaic cysts
Under adverse, incongruous, or unsuitable environments, an amoeba may turn into a cyst (Galileo, 1). This “encystment” occurs to keep the amoeba alive until it reaches a preferred area. Then the organism will secrete a special membrane. This membrane is called a cyst membrane and will enclose it thoroughly (Galileo, 1). Also, the amoeba will become spherical, and will lose a tremendous amount of the amoebae water (Galileo, 1). An adversative environment may mean an environment that’s too warm, cold, or salty for the amoeba.
Cysts have a very similar function to the function of bacterial spores (Salyers/Dixie, 1). These both are defense mechanisms that help the organisms survive. In some adverse places where the organisms would typically expire in their reproducing form, the defenses are great and will keep the organism alive (Salyers/Dixie, 1). The amoeba will not be able to replicate in cyst form, however, and this can be a problem. If an amoeba is kept in an adverse environment as a cyst, the amoeba will perish and will not be able to reproduce other amoebae (Salyers/Dixie, 1).
Amoebae reproduce with binary fission (Blake, 1). Their generation times can be very low. Some generation times can be about a day, others about seven hours. The lowest generation time ever recorded was about two hours. It’s also debated that some rare amoebae can reproduce both sexually and asexually.
### New type of amoeba
Recently, a new type of marine amoeba was found. It was tested for salinity tolerance and it was found to withstand 0%c to 150%c salt without affecting reproduction (Hauer, 1). This amoeba was also able to grow within a range of 0%c to 138%c salt (Hauer, 1). This is unusual because some other amoebae couldn’t take that much at all. Some freshwater amoebae were destroyed at a very low level of concentration of salt. Other marine amoebae and a few freshwater amoebae could stand up to salt concentration in the hundred percentage range but then at 138% concentration salt the amoebae became domed, went into cyst form, or became wrinkled and were destroyed (Hauer, 1). This shows the diversity of amoebae, and that some amoebae will react differently to salt. Therefore the scientist(s) must choose one and only one type of amoeba if the scientist(s) wants accurate results.
## Marine amoebae
Marine amoebae lack contractile vacuoles and their enzymes and organelles are not damaged by the salt water in the sea or ocean (Blake, 1). Some also live in salt swamps, salty lakes, and salty rivers or streams. When an amoeba is put on a microscope slide, it will usually tend to try to get away from the microscope light (Granville, 11/14/2006).
# Amoebas pathogenic to humans
- Entamoeba histolytica
- Naegleria fowleri
- Acanthamoeba
- Balamuthia mandrillaris
- Hartmannella | Amoeba
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Amoeba (sometimes amœba or ameba, plural amoebae) is a genus of protozoa that moves by means of temporary projections called pseudopods, and is well-known as a representative unicellular organism. The word amoeba or ameba is variously used to refer to it and its close relatives, now grouped as the Amoebozoa, or to all protozoa that move using pseudopods, otherwise termed amoeboids. The amoeba was first discovered by August Johann Rösel von Rosenhof in 1755.[1]
# Habitat and study
Amoeba itself is found in decaying vegetation in fresh and salt water, wet soil, and animals. Due to the ease with which they may be obtained and kept alive they are common objects of study, both as representative protozoa and to demonstrate cell structure and function. The cells have several lobose pseudopods, with one large tubular pseudopod at the anterior and several secondary ones branching to the sides. The most famous species, Amoeba proteus, is 700-800 μm in length but amoebae vary from as large as a millimeter (Amoeba dubia which is visible to the naked eye) to far smaller than 700 μm. Its most recognizable features include a single nucleus and simple contractile vacuole to maintain osmotic pressure. The amoeba obtains its food through phagocytosis. Amoebas reproduce through binary fission.
Early naturalists referred to Amoeba as the Proteus animalcule after the Greek god Proteus who could change his shape. The name "amibe" was given to it by Bery St. Vincent, from the Greek amoibè, meaning change.
# Anatomy
An amoeba, from the order Amoebida, class Mastigophora phylum sarcodina protozoa,[2] is a single-celled organism. They live in freshwater stagnant ponds, soil, streams, the ocean, and the bodies of other organisms. Some of the largest amoebae are about 1mm across, which means a human being would barely be able to see it with the naked eye. The word amoeba means “to change” in Greek (Encyclopedia of Science, 1).
An amoeba is composed of several different parts. One is a cell membrane, which is an amoeba’s outer covering. Then there is the nucleus, the central organelle, or brain, and the common animal cell organelles (Dery, 1). An amoeba also has endoplasm and ectoplasm, and the two specialized types of vacuoles (Dery, 1). See Figure 1 (Dery, 1).
The ectoplasm is the exterior gel of the amoeba and the endoplasm is the interior fluid. These two components are used for storing organelles and undergoing pseudopodial extension (see page seven, pseudopodial movement); locomotion of the amoeba and capturing food. See Figure 2. (Aardvark-Catalyst, 163-164).
The two vacuoles are the digestive and food vacuoles. The food vacuole is formed when the amoeba undertakes the process of phagocytosis (pseudopodia surrounding food [Gale, 1]) (see Figure 3) (Aardvark-Catalyst, 163). Once the food vacuole is formed, it becomes a digestive vacuole, which is responsible for breaking down the food into energy (Encyclopedia of Science, 1). Also, an amoeba has a contractile vacuole, which is responsible for pumping water in and out of the amoeba.
Amoebae are diverse in many ways. For example, they drastically range in size from 1mm across (Blake, 1). Some traits even change in different environments, making it hard to tell the amoebae apart (Blake, 1). Also, some amoebae are carnivorous, some are herbivorous, and some are even omnivorous. Then, there are the parasitic ones (Blake, 1), which can live in one’s liver, lungs, brain- even heart (Innvista, 1)! These will become a cyst until they go inside of you, then they become a trophozite, their replicating forms (1).
# Stimuli
## Hypertonic and hypotonic solutions
Like most pies, amoebae are adversely affected by excessive osmotic pressure, like very salty or very fresh water. When an amoeba is put into salt water with enough concentration, some of its organelles, like the contractile vacuole, are damaged. As the amoeba prevents the salt from entering, instead the solution will pull water out of the amoeba, concentrating the salts inside. When this happens the amoeba will appear to shrink.
If a brine amoeba is put into fresh water and it is not a cyst at the time, its contractile vacuole will burst (Do, 1). This is because the vacuole’s job is to create a solution isotonic to the amoeba's environment. If the salt concentration inside the vacuole is too high, it will trigger water absorption. (Do, 1). Soon, the vacuole will burst before it has reached equilibrium. This means the amoeba will also burst. See Figure 4. (Do, 1).
Also, some enzymes might be damaged in the process, including digestive enzymes used in phagocytosis. (Gale, 1). The amoeba will ingest food but be unable to digest it to extract energy. The amoeba then will perish.
## Amoebaic cysts
Under adverse, incongruous, or unsuitable environments, an amoeba may turn into a cyst (Galileo, 1). This “encystment” occurs to keep the amoeba alive until it reaches a preferred area. Then the organism will secrete a special membrane. This membrane is called a cyst membrane and will enclose it thoroughly (Galileo, 1). Also, the amoeba will become spherical, and will lose a tremendous amount of the amoebae water (Galileo, 1). An adversative environment may mean an environment that’s too warm, cold, or salty for the amoeba.
Cysts have a very similar function to the function of bacterial spores (Salyers/Dixie, 1). These both are defense mechanisms that help the organisms survive. In some adverse places where the organisms would typically expire in their reproducing form, the defenses are great and will keep the organism alive (Salyers/Dixie, 1). The amoeba will not be able to replicate in cyst form, however, and this can be a problem. If an amoeba is kept in an adverse environment as a cyst, the amoeba will perish and will not be able to reproduce other amoebae (Salyers/Dixie, 1).
Amoebae reproduce with binary fission (Blake, 1). Their generation times can be very low. Some generation times can be about a day, others about seven hours. The lowest generation time ever recorded was about two hours. It’s also debated that some rare amoebae can reproduce both sexually and asexually.
### New type of amoeba
Recently, a new type of marine amoeba was found. It was tested for salinity tolerance and it was found to withstand 0%c to 150%c salt without affecting reproduction (Hauer, 1). This amoeba was also able to grow within a range of 0%c to 138%c salt (Hauer, 1). This is unusual because some other amoebae couldn’t take that much at all. Some freshwater amoebae were destroyed at a very low level of concentration of salt. Other marine amoebae and a few freshwater amoebae could stand up to salt concentration in the hundred percentage range but then at 138% concentration salt the amoebae became domed, went into cyst form, or became wrinkled and were destroyed (Hauer, 1). This shows the diversity of amoebae, and that some amoebae will react differently to salt. Therefore the scientist(s) must choose one and only one type of amoeba if the scientist(s) wants accurate results.
## Marine amoebae
Marine amoebae lack contractile vacuoles and their enzymes and organelles are not damaged by the salt water in the sea or ocean (Blake, 1). Some also live in salt swamps, salty lakes, and salty rivers or streams. When an amoeba is put on a microscope slide, it will usually tend to try to get away from the microscope light (Granville, 11/14/2006).
# Amoebas pathogenic to humans
- Entamoeba histolytica
- Naegleria fowleri
- Acanthamoeba
- Balamuthia mandrillaris
- Hartmannella | https://www.wikidoc.org/index.php/Amoeba | |
e960e9e489b3694383ca832dbf0a87221f884436 | wikidoc | Ampere | Ampere
The ampere, in practice often shortened to amp, (symbol: A) is a unit of electric current, or amount of electric charge per second. The ampere is an SI base unit, and is named after André-Marie Ampère, one of the main discoverers of electromagnetism.
# Definition
The ampere is a constant current which, if maintained in two straight parallel conductors of infinite length, of negligible circular cross section, and placed 1 metre apart in a vacuum, would produce between these conductors a force equal to 2×10–7 newton per metre of length. For a description of this force law, see Serway. See also Ampère's force law.
The ampere is a base unit, along with the metre, kelvin, second, mole, candela and the kilogram: it is defined without reference to the quantity of electric charge.
The unit of charge, the coulomb, is defined to be the amount of charge displaced by a one ampere current per unit time of one second. Conversely, an ampere is one coulomb of charge going past a given point in the duration of one second; that is, in general, charge Q is determined by steady current I flowing per unit time t as:
# Realization
The ampere is most accurately realized using a watt balance, but is in practice maintained via Ohm's Law from the units of EMF and resistance, the volt and the ohm, since the latter two can be tied to physical phenomena that are relatively easy to reproduce, the Josephson junction and the quantum Hall effect, respectively. The official realization of a standard ampere is discussed in NIST Special publication 330 Barry N Taylor (editor) Appendix 2, p. 56.
# Proposed future definition
Since a coulomb is approximately equal to 6.24150948×1018 elementary charges, one ampere is approximately equivalent to 6.24150948×1018 elementary charges, such as electrons, moving past a boundary in one second.
As with other SI base units, there have been proposals to redefine the kilogram in such a way as to define some presently measured physical constants to fixed values. One proposed definition of the kilogram is:
The kilogram is the mass which would be accelerated at precisely 2×10-7 m/s2 if subjected to the per metre force between two straight parallel conductors of infinite length, of negligible circular cross section, placed 1 metre apart in vacuum, through which flow a constant current of exactly 6 241 509 479 607 717 888 elementary charges per second.
This redefinition of the kilogram has the effect of fixing the elementary charge to be e = 1.60217653Template:E C and would result in a functionally equivalent definition for the coulomb as being the sum of exactly 6 241 509 479 607 717 888 elementary charges and the ampere as being the electrical current of exactly 6 241 509 479 607 717 888 elementary charges per second. This is consistent with the current 2002 CODATA value for the elementary charge which is 1.60217653×10-19 ± 0.00000014×10-19 C.
## CIPM recommendation
International Committee for Weights and Measures (CIPM) Recommendation 1 (CI-2005):
Preparative steps towards new definitions of the kilogram, the ampere, the
kelvin and the mole in terms of fundamental constants
The International Committee for Weights and Measures (CIPM),
- approve in principle the preparation of new definitions and mises en pratique of the kilogram, the ampere and the kelvin so that if the results of experimental measurements over the next few years are indeed acceptable, all having been agreed with the various Consultative Committees and other relevant bodies, the CIPM can prepare proposals to be put to Member States of the Metre Convention in time for possible adoption by the 24th CGPM in 2011;
- give consideration to the possibility of redefining, at the same time, the mole in terms of a fixed value of the Avogadro constant;
- prepare a Draft Resolution that may be put to the 23rd CGPM in 2007 to alert Member States to these activities; | Ampere
The ampere, in practice often shortened to amp, (symbol: A) is a unit of electric current, or amount of electric charge per second. The ampere is an SI base unit, and is named after André-Marie Ampère, one of the main discoverers of electromagnetism.
# Definition
The ampere is a constant current which, if maintained in two straight parallel conductors of infinite length, of negligible circular cross section, and placed 1 metre apart in a vacuum, would produce between these conductors a force equal to 2×10–7 newton per metre of length.[1][2] For a description of this force law, see Serway.[3] See also Ampère's force law.
The ampere is a base unit, along with the metre, kelvin, second, mole, candela and the kilogram: it is defined without reference to the quantity of electric charge.
The unit of charge, the coulomb, is defined to be the amount of charge displaced by a one ampere current per unit time of one second.[4] Conversely, an ampere is one coulomb of charge going past a given point in the duration of one second; that is, in general, charge Q is determined by steady current I flowing per unit time t as:
# Realization
The ampere is most accurately realized using a watt balance, but is in practice maintained via Ohm's Law from the units of EMF and resistance, the volt and the ohm, since the latter two can be tied to physical phenomena that are relatively easy to reproduce, the Josephson junction and the quantum Hall effect, respectively. The official realization of a standard ampere is discussed in NIST Special publication 330 Barry N Taylor (editor) Appendix 2, p. 56.
# Proposed future definition
Since a coulomb is approximately equal to 6.24150948×1018 elementary charges, one ampere is approximately equivalent to 6.24150948×1018 elementary charges, such as electrons, moving past a boundary in one second.
As with other SI base units, there have been proposals to redefine the kilogram in such a way as to define some presently measured physical constants to fixed values. One proposed definition of the kilogram is:
The kilogram is the mass which would be accelerated at precisely 2×10-7 m/s2 if subjected to the per metre force between two straight parallel conductors of infinite length, of negligible circular cross section, placed 1 metre apart in vacuum, through which flow a constant current of exactly 6 241 509 479 607 717 888 elementary charges per second.
This redefinition of the kilogram has the effect of fixing the elementary charge to be e = 1.60217653Template:E C and would result in a functionally equivalent definition for the coulomb as being the sum of exactly 6 241 509 479 607 717 888 elementary charges and the ampere as being the electrical current of exactly 6 241 509 479 607 717 888 elementary charges per second. This is consistent with the current 2002 CODATA value for the elementary charge which is 1.60217653×10-19 ± 0.00000014×10-19 C.
## CIPM recommendation
International Committee for Weights and Measures (CIPM) Recommendation 1 (CI-2005):
Preparative steps towards new definitions of the kilogram, the ampere, the
kelvin and the mole in terms of fundamental constants
The International Committee for Weights and Measures (CIPM),
- approve in principle the preparation of new definitions and mises en pratique of the kilogram, the ampere and the kelvin so that if the results of experimental measurements over the next few years are indeed acceptable, all having been agreed with the various Consultative Committees and other relevant bodies, the CIPM can prepare proposals to be put to Member States of the Metre Convention in time for possible adoption by the 24th CGPM in 2011;
- give consideration to the possibility of redefining, at the same time, the mole in terms of a fixed value of the Avogadro constant;
- prepare a Draft Resolution that may be put to the 23rd CGPM in 2007 to alert Member States to these activities;
Template:SI unit lowercase | https://www.wikidoc.org/index.php/Ampere | |
3ac57aadbd80a1ec321151f58a56351a6c840c9f | wikidoc | Amylin | Amylin
Amylin, or islet amyloid polypeptide (IAPP), is a 37-residue peptide hormone. It is cosecreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1 (insulin:amylin). Amylin plays a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels.
IAPP is processed from an 89-residue coding sequence. Proislet amyloid polypeptide (proIAPP, proamylin, proislet protein) is produced in the pancreatic beta cells (β-cells) as a 67 amino acid, 7404 Dalton pro-peptide and undergoes post-translational modifications including protease cleavage to produce amylin.
# Synthesis
ProIAPP consists of 67 amino acids, which follow a 22 amino acid signal peptide which is rapidly cleaved after translation of the 89 amino acid coding sequence. The human sequence (from N-terminus to C-terminus) is:
(MGILKLQVFLIVLSVALNHLKA) TPIESHQVEKR^ KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTYG^ KR^ NAVEVLKREPLNYLPL.
Once released from the signal peptide, it undergoes additional proteolysis and posttranslational modification (indicated by ^). 11 amino acids are removed from the N-terminus by the enzyme proprotein convertase 2 (PC2) while 16 are removed from the C-terminus of the proIAPP molecule by proprotein convertase 1/3 (PC1/3). At the C-terminus Carboxypeptidase E then removes the terminal lysine and arginine residues. The terminal glycine amino acid that results from this cleavage allows the enzyme peptidylglycine alpha-amidating monooxygenase (PAM) to add an amine group. Finally, a disulfide bond is formed between cysteine residues numbers 2 and 7. After this the transformation from the precursor protein proIAPP to the biologically active IAPP is complete (IAPP sequence: KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY).
# Regulation
Insulin and IAPP are regulated by similar factors since they share a common regulatory promoter motif. The IAPP promoter is also activated by stimuli which do not affect insulin, such as tumor necrosis factor alpha and fatty acids. One of the defining features of Type 2 diabetes is insulin resistance. This is a condition wherein the body is unable to utilize insulin effectively, resulting in increased insulin production; since proinsulin and proIAPP are cosecreted, this results in an increase in the production of proIAPP as well.
Although little is known about IAPP regulation, its connection to insulin indicates that regulatory mechanisms that affect insulin also affect IAPP. Thus blood glucose levels play an important role in regulation of proIAPP synthesis.
# Function
Amylin functions as part of the endocrine pancreas and contributes to glycemic control. The peptide is secreted from the pancreatic islets into the blood circulation and is cleared by peptidases in the kidney. It is not found in the urine.
Amylin's metabolic function is well-characterized as an inhibitor of the appearance of nutrient in the plasma. It thus functions as a synergistic partner to insulin, with which it is cosecreted from pancreatic beta cells in response to meals. The overall effect is to slow the rate of appearance (Ra) of glucose in the blood after eating; this is accomplished via coordinate slowing down gastric emptying, inhibition of digestive secretion , and a resulting reduction in food intake. Appearance of new glucose in the blood is reduced by inhibiting secretion of the gluconeogenic hormone glucagon. These actions, which are mostly carried out via a glucose-sensitive part of the brain stem, the area postrema, may be over-ridden during hypoglycemia. They collectively reduce the total insulin demand.
Amylin also acts in bone metabolism, along with the related peptides calcitonin and calcitonin gene related peptide.
Rodent amylin knockouts do not have a normal reduction of appetite following food consumption. Because it is an amidated peptide, like many neuropeptides, it is believed to be responsible for the effect on appetite.
# Structure
The human form of IAPP has the amino acid sequence KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY, with a disulfide bridge between cysteine residues 2 and 7. Both the amidated C-terminus and the disulfide bridge are necessary for the full biological activity of amylin. IAPP is capable of forming amyloid fibrils in vitro. Within the fibrillization reaction, the early prefibrillar structures are extremely toxic to beta-cell and insuloma cell cultures. Later amyloid fiber structures also seem to have some cytotoxic effect on cell cultures. Studies have shown that fibrils are the end product and not necessarily the most toxic form of amyloid proteins/peptides in general. A non-fibril forming peptide (1–19 residues of human amylin) is toxic like the full-length peptide but the respective segment of rat amylin is not. It was also demonstrated by solid-state NMR spectroscopy that the fragment 20-29 of the human-amylin fragments membranes. Rats and mice have six substitutions (three of which are proline substitions at positions 25, 28 and 29) that are believed to prevent the formation of amyloid fibrils, although not completely as seen by its propensity to form amyloid fibrils in vitro. Rat IAPP is nontoxic to beta-cells when overexpressed in transgenic rodents.
# History
IAPP was identified independently by two groups as the major component of diabetes-associated islet amyloid deposits in 1987.
The difference in nomenclature is largely geographical; European researchers tend to prefer IAPP whereas American researchers tend to prefer amylin. Some researchers discourage the use of "amylin" on the grounds that it may be confused with the pharmaceutical company.
# Clinical significance
ProIAPP has been linked to Type 2 diabetes and the loss of islet β-cells. Islet amyloid formation, initiated by the aggregation of proIAPP, may contribute to this progressive loss of islet β-cells. It is thought that proIAPP forms the first granules that allow for IAPP to aggregate and form amyloid which may lead to amyloid-induced apoptosis of β-cells.
IAPP is cosecreted with insulin. Insulin resistance in Type 2 diabetes produces a greater demand for insulin production which results in the secretion of proinsulin. ProIAPP is secreted simultaneously, however, the enzymes that convert these precursor molecules into insulin and IAPP, respectively, are not able to keep up with the high levels of secretion, ultimately leading to the accumulation of proIAPP.
In particular, the impaired processing of proIAPP that occurs at the N-terminal cleavage site is a key factor in the initiation of amyloid. Post-translational modification of proIAPP occurs at both the carboxy terminus and the amino terminus, however, the processing of the amino terminus occurs later in the secretory pathway. This might be one reason why it is more susceptible to impaired processing under conditions where secretion is in high demand. Thus, the conditions of Type 2 diabetes—high glucose concentrations and increased secretory demand for insulin and IAPP—could lead to the impaired N-terminal processing of proIAPP. The unprocessed proIAPP can then serve as the nidus upon which IAPP can accumulate and form amyloid.
The amyloid formation might be a major mediator of apoptosis, or programmed cell death, in the islet β-cells. Initially, the proIAPP aggregates within secretory vesicles inside the cell. The proIAPP acts as a seed, collecting matured IAPP within the vesicles, forming intracellular amyloid. When the vesicles are released, the amyloid grows as it collects even more IAPP outside the cell. The overall effect is an apoptosis cascade initiated by the influx of ions into the β-cells.
In summary, impaired N-terminal processing of proIAPP is an important factor initiating amyloid formation and β-cell death. These amyloid deposits are pathological characteristics of the pancreas in Type 2 diabetes. However, it is still unclear as to whether amyloid formation is involved in or merely a consequence of type 2 diabetes. Nevertheless, it is clear that amyloid formation reduces working β-cells in patients with Type 2 diabetes. This suggests that repairing proIAPP processing may help to prevent β-cell death, thereby offering hope as a potential therapeutic approach for Type 2 diabetes.
Amyloid deposits deriving from islet amyloid polypeptide (IAPP, or amylin) are commonly found in pancreatic islets of patients suffering diabetes mellitus type 2, or containing an insulinoma cancer. While the association of amylin with the development of type 2 diabetes has been known for some time, its direct role as the cause has been harder to establish. Recent results suggest that amylin, like the related beta-amyloid (Abeta) associated with Alzheimer's disease, can induce apoptotic cell-death in insulin-producing beta cells, an effect that may be relevant to the development of type 2 diabetes.
A 2008 study reported a synergistic effect for weight loss with leptin and amylin coadministration in diet-induced obese rats by restoring hypothalamic sensitivity to leptin. However, in clinical trials, the study was halted at Phase 2 in 2011 when a problem involving antibody activity that might have neutralized the weight-loss effect of metreleptin in two patients who took the drug in a previously completed clinical study. The study combined metreleptin, a version of the human hormone leptin, and pramlintide, which is Amylin’s diabetes drug Symlin, into a single obesity therapy. Finally, a recent proteomics study showed that human amylin shares common toxicity targets with beta-amyloid (Abeta), providing evidence that type 2 diabetes and Alzheimer's disease share common toxicity mechanisms.
# Pharmacology
A synthetic analog of human amylin with proline substitutions in positions 25, 26 and 29, or pramlintide (brand name Symlin), was approved in 2005 for adult use in patients with both diabetes mellitus type 1 and diabetes mellitus type 2. Insulin and pramlintide, injected separately but both before a meal, work together to control the post-prandial glucose excursion.
Amylin is degraded in part by insulin-degrading enzyme.
# Receptors
There appear to be at least three distinct receptor complexes that amylin binds to with high affinity. All three complexes contain the calcitonin receptor at the core, plus one of three receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3. | Amylin
Amylin, or islet amyloid polypeptide (IAPP), is a 37-residue peptide hormone.[1] It is cosecreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1 (insulin:amylin). Amylin plays a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels.
IAPP is processed from an 89-residue coding sequence. Proislet amyloid polypeptide (proIAPP, proamylin, proislet protein) is produced in the pancreatic beta cells (β-cells) as a 67 amino acid, 7404 Dalton pro-peptide and undergoes post-translational modifications including protease cleavage to produce amylin.[2]
# Synthesis
ProIAPP consists of 67 amino acids, which follow a 22 amino acid signal peptide which is rapidly cleaved after translation of the 89 amino acid coding sequence. The human sequence (from N-terminus to C-terminus) is:
(MGILKLQVFLIVLSVALNHLKA) TPIESHQVEKR^ KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTYG^ KR^ NAVEVLKREPLNYLPL.[2][3]
Once released from the signal peptide, it undergoes additional proteolysis and posttranslational modification (indicated by ^). 11 amino acids are removed from the N-terminus by the enzyme proprotein convertase 2 (PC2) while 16 are removed from the C-terminus of the proIAPP molecule by proprotein convertase 1/3 (PC1/3).[4] At the C-terminus Carboxypeptidase E then removes the terminal lysine and arginine residues.[5] The terminal glycine amino acid that results from this cleavage allows the enzyme peptidylglycine alpha-amidating monooxygenase (PAM) to add an amine group. Finally, a disulfide bond is formed between cysteine residues numbers 2 and 7.[6] After this the transformation from the precursor protein proIAPP to the biologically active IAPP is complete (IAPP sequence: KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY).[2]
# Regulation
Insulin and IAPP are regulated by similar factors since they share a common regulatory promoter motif.[7] The IAPP promoter is also activated by stimuli which do not affect insulin, such as tumor necrosis factor alpha[8] and fatty acids.[9] One of the defining features of Type 2 diabetes is insulin resistance. This is a condition wherein the body is unable to utilize insulin effectively, resulting in increased insulin production; since proinsulin and proIAPP are cosecreted, this results in an increase in the production of proIAPP as well.
Although little is known about IAPP regulation, its connection to insulin indicates that regulatory mechanisms that affect insulin also affect IAPP. Thus blood glucose levels play an important role in regulation of proIAPP synthesis.
# Function
Amylin functions as part of the endocrine pancreas and contributes to glycemic control. The peptide is secreted from the pancreatic islets into the blood circulation and is cleared by peptidases in the kidney. It is not found in the urine.
Amylin's metabolic function is well-characterized as an inhibitor of the appearance of nutrient [especially glucose] in the plasma.[10] It thus functions as a synergistic partner to insulin, with which it is cosecreted from pancreatic beta cells in response to meals. The overall effect is to slow the rate of appearance (Ra) of glucose in the blood after eating; this is accomplished via coordinate slowing down gastric emptying, inhibition of digestive secretion [gastric acid, pancreatic enzymes, and bile ejection], and a resulting reduction in food intake. Appearance of new glucose in the blood is reduced by inhibiting secretion of the gluconeogenic hormone glucagon. These actions, which are mostly carried out via a glucose-sensitive part of the brain stem, the area postrema, may be over-ridden during hypoglycemia. They collectively reduce the total insulin demand.[11]
Amylin also acts in bone metabolism, along with the related peptides calcitonin and calcitonin gene related peptide.[10]
Rodent amylin knockouts do not have a normal reduction of appetite following food consumption.[citation needed] Because it is an amidated peptide, like many neuropeptides, it is believed to be responsible for the effect on appetite.
# Structure
The human form of IAPP has the amino acid sequence KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY, with a disulfide bridge between cysteine residues 2 and 7. Both the amidated C-terminus and the disulfide bridge are necessary for the full biological activity of amylin.[6] IAPP is capable of forming amyloid fibrils in vitro. Within the fibrillization reaction, the early prefibrillar structures are extremely toxic to beta-cell and insuloma cell cultures.[6] Later amyloid fiber structures also seem to have some cytotoxic effect on cell cultures. Studies have shown that fibrils are the end product and not necessarily the most toxic form of amyloid proteins/peptides in general. A non-fibril forming peptide (1–19 residues of human amylin) is toxic like the full-length peptide but the respective segment of rat amylin is not.[12][13][14] It was also demonstrated by solid-state NMR spectroscopy that the fragment 20-29 of the human-amylin fragments membranes.[15] Rats and mice have six substitutions (three of which are proline substitions at positions 25, 28 and 29) that are believed to prevent the formation of amyloid fibrils, although not completely as seen by its propensity to form amyloid fibrils in vitro.[16][17] Rat IAPP is nontoxic to beta-cells when overexpressed in transgenic rodents.
# History
IAPP was identified independently by two groups as the major component of diabetes-associated islet amyloid deposits in 1987.[18][19]
The difference in nomenclature is largely geographical; European researchers tend to prefer IAPP whereas American researchers tend to prefer amylin. Some researchers discourage the use of "amylin" on the grounds that it may be confused with the pharmaceutical company.[citation needed]
# Clinical significance
ProIAPP has been linked to Type 2 diabetes and the loss of islet β-cells.[20] Islet amyloid formation, initiated by the aggregation of proIAPP, may contribute to this progressive loss of islet β-cells. It is thought that proIAPP forms the first granules that allow for IAPP to aggregate and form amyloid which may lead to amyloid-induced apoptosis of β-cells.
IAPP is cosecreted with insulin. Insulin resistance in Type 2 diabetes produces a greater demand for insulin production which results in the secretion of proinsulin.[21] ProIAPP is secreted simultaneously, however, the enzymes that convert these precursor molecules into insulin and IAPP, respectively, are not able to keep up with the high levels of secretion, ultimately leading to the accumulation of proIAPP.
In particular, the impaired processing of proIAPP that occurs at the N-terminal cleavage site is a key factor in the initiation of amyloid.[21] Post-translational modification of proIAPP occurs at both the carboxy terminus and the amino terminus, however, the processing of the amino terminus occurs later in the secretory pathway. This might be one reason why it is more susceptible to impaired processing under conditions where secretion is in high demand.[5] Thus, the conditions of Type 2 diabetes—high glucose concentrations and increased secretory demand for insulin and IAPP—could lead to the impaired N-terminal processing of proIAPP. The unprocessed proIAPP can then serve as the nidus upon which IAPP can accumulate and form amyloid.[22]
The amyloid formation might be a major mediator of apoptosis, or programmed cell death, in the islet β-cells.[22] Initially, the proIAPP aggregates within secretory vesicles inside the cell. The proIAPP acts as a seed, collecting matured IAPP within the vesicles, forming intracellular amyloid. When the vesicles are released, the amyloid grows as it collects even more IAPP outside the cell. The overall effect is an apoptosis cascade initiated by the influx of ions into the β-cells.
In summary, impaired N-terminal processing of proIAPP is an important factor initiating amyloid formation and β-cell death. These amyloid deposits are pathological characteristics of the pancreas in Type 2 diabetes. However, it is still unclear as to whether amyloid formation is involved in or merely a consequence of type 2 diabetes.[21] Nevertheless, it is clear that amyloid formation reduces working β-cells in patients with Type 2 diabetes. This suggests that repairing proIAPP processing may help to prevent β-cell death, thereby offering hope as a potential therapeutic approach for Type 2 diabetes.
Amyloid deposits deriving from islet amyloid polypeptide (IAPP, or amylin) are commonly found in pancreatic islets of patients suffering diabetes mellitus type 2, or containing an insulinoma cancer. While the association of amylin with the development of type 2 diabetes has been known for some time,[23] its direct role as the cause has been harder to establish. Recent results suggest that amylin, like the related beta-amyloid (Abeta) associated with Alzheimer's disease, can induce apoptotic cell-death in insulin-producing beta cells, an effect that may be relevant to the development of type 2 diabetes.[24]
A 2008 study reported a synergistic effect for weight loss with leptin and amylin coadministration in diet-induced obese rats by restoring hypothalamic sensitivity to leptin.[25] However, in clinical trials, the study was halted at Phase 2 in 2011 when a problem involving antibody activity that might have neutralized the weight-loss effect of metreleptin in two patients who took the drug in a previously completed clinical study. The study combined metreleptin, a version of the human hormone leptin, and pramlintide, which is Amylin’s diabetes drug Symlin, into a single obesity therapy.[26] Finally, a recent proteomics study showed that human amylin shares common toxicity targets with beta-amyloid (Abeta), providing evidence that type 2 diabetes and Alzheimer's disease share common toxicity mechanisms.[27]
# Pharmacology
A synthetic analog of human amylin with proline substitutions in positions 25, 26 and 29, or pramlintide (brand name Symlin), was approved in 2005 for adult use in patients with both diabetes mellitus type 1 and diabetes mellitus type 2. Insulin and pramlintide, injected separately but both before a meal, work together to control the post-prandial glucose excursion.[28]
Amylin is degraded in part by insulin-degrading enzyme.[29]
# Receptors
There appear to be at least three distinct receptor complexes that amylin binds to with high affinity. All three complexes contain the calcitonin receptor at the core, plus one of three receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3.[30] | https://www.wikidoc.org/index.php/Amylin | |
b0a013a1cc93cabd8cec25fa8d1f26843c4d62d1 | wikidoc | Ancrod | Ancrod
# Overview
Ancrod (current brand name: Viprinex) is a defibrinogenating agent derived from the venom of the Malayan pit viper. The defribrinogenation of blood results in an anticoagulant effect. Currently, Viprinex®/ancrod is not approved or marketed in any country, but is being investigated as a stroke treatment in worldwide clinical trials. In January 2005, the U.S. FDA granted a 'fast-track status' for investigation of ancrod use in patients suffering from acute ischemic stroke, a life threatening condition caused by the blockage of blood vessels supplying blood and oxygen to portions of the brain, for which phase III trials are currently being conducted.
# Marketing history
Under the brand name Arwin®, ancrod was marketed in Germany and Austria, where it was withdrawn in the 1980s after it was used for some decades. Arwin® was a brand name of Knoll Pharma. Neurobiological Technologies, Inc., currently holds the worldwide rights to ancrod under the brand name Viprinex®. Previously, the rights to Viprinex® were respectively held by Empire Pharmaceuticals, Inc., Abbott Laboratories, and Knoll AG, developers of this investigational drug.
Neurobiological Technologies, Inc. (NTI) has signed agreements with Nordmark Arzneimittel GmbH & Co KG (Nordmark) and Baxter Pharmaceutical Solutions, LLC (Baxter) to manufacture, fill and package Viprinex® for NTI's Phase III clinical trials in acute ischemic stroke. Nordmark will manufacture the biological active ingredient, ancrod. Date of this agreement was 1st. August 2005.
# Chemistry and pharmacology
Ancrod has a triple mode of action. The exact structure and chemical data such as molecular weight are unknown, but it has been elaborated that the glycosylation of the molecule is an important factor. Glycosylation is remarkably homogenous with the major oligosaccharide accounting for approximately 90% of the total sugar content. Some in vitro reactions have been explored in very detail (see ref. #2, www.blckwell-synergy). Experimentally it was found that ancrod's actions are FAD dependent and that the substance has interesting apoptotic properties (causing programmed cell death), which still remain to be elaborated.
Ancrod is prepared from the crude venom of the Malayan pit viper (Agkistrodon rhodostoma, also termed Calloselasma rhodostoma) and belongs to the group of proteolytic enzymes. Ancrod may also be found in the venoms of many poisonous snakes (crotalids, elapids and viperids) in general, but the Malayan pit viper is most suitable due to a high concentration of ancrod in its venom. For its preparation a snake farm, very skilled and well trained staff (for milking the highly poisonous snakes), and special production facilities are required to purify the enzyme.
The halflife of ancrod is 3 to 5 hours and the drug is cleared from plasma, mainly renally.
Due to its special mode of action (see below) and its price, Arwin® was never been used as 'normal' anticoagulant such as heparin, but only for the symptomatic treatment of moderate to severe forms of peripheral arterial circulatory disorders such as those resulting from years of heavy smoking and/or arteriosclerosis.
The substance is intended for parenteral, namely subcutaneous (s.c.) injection and intravenous (i.v.) infusion, and indirectly inhibits aggregation, adhesion, and release of thrombocytes mediated through the action of a fibrinogen degradation product (FDP). It also cleaves and therefore inactivates a significant part of circulating plasma fibrinogen. Fibrinogen is often found in increased concentrations in arteriae with impaired circulation. This leads to a pathologically increased blood viscosity and thereby to a worsening of symptoms of the circulation disorder (more intense pain, decreased mobility of the limb and decreased temperature, need for partial or even total limb amputation). The blood viscosity in patients receiving ancrod is progressively reduced by 30 to 40% of the pretreatment levels. The decreased viscosity is directly attributable to lowered fibrinogen levels and leads to important improvements in blood flow and perfusion of the microcirculation. Erythrocyte flexibility is not affected by normal doses of ancrod. The rheological changes are readily maintained and the viscosity approaches pretreatment values very slowly (within about 10 days) after stopping ancrod. One of the cleavage fibrinogen products, termed 'desAA-Fibrin', acts as cofactor for the tPA-induced plasminogen activation and an increased fibrinolysis results in return (profibrinolytic activity of ancrod).
Ancrod decreases the blood viscosity in affected arteries, leads to less intense pain, improves physical limb mobility, and facilitates physical and ergo therapy. Finally, ancrod decreases the likelihood of local thrombotic events.
The above mentioned mechanisms also account for ancrod's activity in other diseases.
Effects on other clotting factors: Unlike thrombin, ancrod does not directly activate Factor XIII, nor does it produce platelet aggregation nor cause the release of ADP, ATP, potassium, nor serotonin from platelets. Platelet counts and survival time remain normal during ancord therapy.
# Indications
## Historical
For the treatment of established deep vein thrombosis; central retinal and branch vein thrombosis; priapism; pulmonary hypertension of embolic origin; embolism after insertion of prosthetic cardiac valves; rethrombosis after thrombolytic therapy and rethrombosis after vascular surgery. It is also indicated for the prevention of deep venous thrombosis after repair of the fractured neck of a femur.
For the treatment of moderate and severe chronic circulatory disorders of peripheral arteries (e.g., arteriosclerosis obliterans, thromboangiitis obliterans, diabetic microangiopathy and Raynaud's phenomenon).
Ancrod has been shown to be useful for maintaining anticoagulation in the presence of Heparin-induced thrombocytopenia (HIT) and thrombosis.
Currently, this drug is not approved nor available. It is being investigated in clinical trials for stroke.
## Studies in early ischemic stroke
In a multicenter, parallel, group sequential, randomized, double-blind, placebo-controlled German study of efficacy and safety of i.v. ancrod given within 6 hours after the onset of acute, ischemic stroke and continued for 5 days (called ESTAT study), the early findings for 800 patients were positive, but as the study was expanded to 1,600 patients, placebo was found to be more effective than ancrod and the study was abruptly terminated, mainly because the mortality in the ancrod group was higher. The smaller American study 'Stroke Treatment with Ancrod Trial (STAT)' confirmed the negative outcome for ischemic stroke. In these studies, patients received a multi-day infusion of Viprinex designed to maintain patients’ fibrinogen level within a targeted range. Currently, a new dosing strategy is being investigated in two international phase III trials as part of the 'Ancrod Stroke Program (ASP).' Each of these studies will enroll 650 patients and assess whether a brief, relatively rapid ancrod infusion with no maintenance dosing will be both effective and safe.
# Contraindications and precautions
- Known bleeding disorders of any origin or any unexplained excessive bleedings in the past.
- Platelet counts of less than 100,000 (even if asymptomatic), exemption : HIT (Heparin- induced thrombocytopenia).
- Planned surgery or short before delivery.
- Active ulcerations of the GIT.
- Any kind of malignant disease.
- Renal stones (increased likelihood of significant urological bleeding).
- Severe and uncontrolled arterial hypertension.
- Active pulmonary tuberculosis.
- Impaired fibrinolysis.
- Severe liver disease.
- Manifest or impending shock.
- I.M.-Injection : Ancrod should not be injected i.m., because of rapid induction of neutralizing antibodies and therefore drug resistance.
## Pregnancy
Category X : Ancrod was not found to be teratogenic in animal studies, but some fetal deaths occurred as a result of placental hemorrhages in animals given high doses; therefore, it should not be used during pregnancy as the defibrinogenation mechanism of ancrod might be expected to interfere with the normal implantation of the fertilized egg.
# Side effects
- Hypersensitivity reactions : Local or generalized skin reactions (rash and urticaria); appearance of neutralizing antibodies to ancrod with partial or total loss of ancrod activity (drug resistance).
- Sometimes pain at injection site (normally mild). This side-effect may be, if necessary, treated with local or oral antihistaminic drugs (e.g., clemastine, or diphenhydramine). Bleeding at injection site, thrombophlebitis at local veins, and (paradoxical) arterial thrombotic events.
- Occasionally deposition of cleaved fibrinogen derivates in the splen resulting in splenomegaly; rupture is possible, if the spleen is palpated too strongly (life-threatening bleeding and need of splenectomy may result).
- Specific side-effects are local and systemic bleeding events. Local bleeding events may be treated with local pressure or surgical dressings, if necessary. Compared with other anticoagulants the risk of systemic bleeding is relatively low. If systemic bleeding is severe enough to warrant fast reversal of ancrod action, fibrinogen should be substituted (please refer to section 'special antidotes').
- Occasionally, increased headache has been found in patients with known migraine.
- Also, chills and fever may occur infrequently.
Thrombocytopenia as side-effect has never been noticed with ancrod in contrast to heparin.
# Availablility
Viprinex® is not currently approved or available. | Ancrod
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Ancrod (current brand name: Viprinex) is a defibrinogenating agent derived from the venom of the Malayan pit viper. The defribrinogenation of blood results in an anticoagulant effect. Currently, Viprinex®/ancrod is not approved or marketed in any country, but is being investigated as a stroke treatment in worldwide clinical trials. In January 2005, the U.S. FDA granted a 'fast-track status' for investigation of ancrod use in patients suffering from acute ischemic stroke, a life threatening condition caused by the blockage of blood vessels supplying blood and oxygen to portions of the brain, for which phase III trials are currently being conducted.
# Marketing history
Under the brand name Arwin®, ancrod was marketed in Germany and Austria, where it was withdrawn in the 1980s after it was used for some decades. Arwin® was a brand name of Knoll Pharma. Neurobiological Technologies, Inc., currently holds the worldwide rights to ancrod under the brand name Viprinex®. Previously, the rights to Viprinex® were respectively held by Empire Pharmaceuticals, Inc., Abbott Laboratories, and Knoll AG, developers of this investigational drug.
Neurobiological Technologies, Inc. (NTI) has signed agreements with Nordmark Arzneimittel GmbH & Co KG (Nordmark) and Baxter Pharmaceutical Solutions, LLC (Baxter) to manufacture, fill and package Viprinex® for NTI's Phase III clinical trials in acute ischemic stroke. Nordmark will manufacture the biological active ingredient, ancrod. Date of this agreement was 1st. August 2005.
# Chemistry and pharmacology
Ancrod has a triple mode of action. The exact structure and chemical data such as molecular weight are unknown, but it has been elaborated that the glycosylation of the molecule is an important factor. Glycosylation is remarkably homogenous with the major oligosaccharide accounting for approximately 90% of the total sugar content. Some in vitro reactions have been explored in very detail (see ref. #2, www.blckwell-synergy). Experimentally it was found that ancrod's actions are FAD dependent and that the substance has interesting apoptotic properties (causing programmed cell death), which still remain to be elaborated.
Ancrod is prepared from the crude venom of the Malayan pit viper (Agkistrodon rhodostoma, also termed Calloselasma rhodostoma) and belongs to the group of proteolytic enzymes. Ancrod may also be found in the venoms of many poisonous snakes (crotalids, elapids and viperids) in general, but the Malayan pit viper is most suitable due to a high concentration of ancrod in its venom. For its preparation a snake farm, very skilled and well trained staff (for milking the highly poisonous snakes), and special production facilities are required to purify the enzyme.
The halflife of ancrod is 3 to 5 hours and the drug is cleared from plasma, mainly renally.
Due to its special mode of action (see below) and its price, Arwin® was never been used as 'normal' anticoagulant such as heparin, but only for the symptomatic treatment of moderate to severe forms of peripheral arterial circulatory disorders such as those resulting from years of heavy smoking and/or arteriosclerosis.
The substance is intended for parenteral, namely subcutaneous (s.c.) injection and intravenous (i.v.) infusion, and indirectly inhibits aggregation, adhesion, and release of thrombocytes mediated through the action of a fibrinogen degradation product (FDP). It also cleaves and therefore inactivates a significant part of circulating plasma fibrinogen. Fibrinogen is often found in increased concentrations in arteriae with impaired circulation. This leads to a pathologically increased blood viscosity and thereby to a worsening of symptoms of the circulation disorder (more intense pain, decreased mobility of the limb and decreased temperature, need for partial or even total limb amputation). The blood viscosity in patients receiving ancrod is progressively reduced by 30 to 40% of the pretreatment levels. The decreased viscosity is directly attributable to lowered fibrinogen levels and leads to important improvements in blood flow and perfusion of the microcirculation. Erythrocyte flexibility is not affected by normal doses of ancrod. The rheological changes are readily maintained and the viscosity approaches pretreatment values very slowly (within about 10 days) after stopping ancrod. One of the cleavage fibrinogen products, termed 'desAA-Fibrin', acts as cofactor for the tPA-induced plasminogen activation and an increased fibrinolysis results in return (profibrinolytic activity of ancrod).
Ancrod decreases the blood viscosity in affected arteries, leads to less intense pain, improves physical limb mobility, and facilitates physical and ergo therapy. Finally, ancrod decreases the likelihood of local thrombotic events.
The above mentioned mechanisms also account for ancrod's activity in other diseases.
Effects on other clotting factors: Unlike thrombin, ancrod does not directly activate Factor XIII, nor does it produce platelet aggregation nor cause the release of ADP, ATP, potassium, nor serotonin from platelets. Platelet counts and survival time remain normal during ancord therapy.
# Indications
## Historical
For the treatment of established deep vein thrombosis; central retinal and branch vein thrombosis; priapism; pulmonary hypertension of embolic origin; embolism after insertion of prosthetic cardiac valves; rethrombosis after thrombolytic therapy and rethrombosis after vascular surgery. It is also indicated for the prevention of deep venous thrombosis after repair of the fractured neck of a femur.
For the treatment of moderate and severe chronic circulatory disorders of peripheral arteries (e.g., arteriosclerosis obliterans, thromboangiitis obliterans, diabetic microangiopathy and Raynaud's phenomenon).
Ancrod has been shown to be useful for maintaining anticoagulation in the presence of Heparin-induced thrombocytopenia (HIT) and thrombosis.
Currently, this drug is not approved nor available. It is being investigated in clinical trials for stroke.
## Studies in early ischemic stroke
In a multicenter, parallel, group sequential, randomized, double-blind, placebo-controlled German study of efficacy and safety of i.v. ancrod given within 6 hours after the onset of acute, ischemic stroke and continued for 5 days (called ESTAT study), the early findings for 800 patients were positive, but as the study was expanded to 1,600 patients, placebo was found to be more effective than ancrod and the study was abruptly terminated, mainly because the mortality in the ancrod group was higher. The smaller American study 'Stroke Treatment with Ancrod Trial (STAT)' confirmed the negative outcome for ischemic stroke. In these studies, patients received a multi-day infusion of Viprinex designed to maintain patients’ fibrinogen level within a targeted range. Currently, a new dosing strategy is being investigated in two international phase III trials as part of the 'Ancrod Stroke Program (ASP).' Each of these studies will enroll 650 patients and assess whether a brief, relatively rapid ancrod infusion with no maintenance dosing will be both effective and safe.
# Contraindications and precautions
- Known bleeding disorders of any origin or any unexplained excessive bleedings in the past.
- Platelet counts of less than 100,000 (even if asymptomatic), exemption : HIT (Heparin- induced thrombocytopenia).
- Planned surgery or short before delivery.
- Active ulcerations of the GIT.
- Any kind of malignant disease.
- Renal stones (increased likelihood of significant urological bleeding).
- Severe and uncontrolled arterial hypertension.
- Active pulmonary tuberculosis.
- Impaired fibrinolysis.
- Severe liver disease.
- Manifest or impending shock.
- I.M.-Injection : Ancrod should not be injected i.m., because of rapid induction of neutralizing antibodies and therefore drug resistance.
## Pregnancy
Category X : Ancrod was not found to be teratogenic in animal studies, but some fetal deaths occurred as a result of placental hemorrhages in animals given high doses; therefore, it should not be used during pregnancy as the defibrinogenation mechanism of ancrod might be expected to interfere with the normal implantation of the fertilized egg.
# Side effects
- Hypersensitivity reactions : Local or generalized skin reactions (rash and urticaria); appearance of neutralizing antibodies to ancrod with partial or total loss of ancrod activity (drug resistance).
- Sometimes pain at injection site (normally mild). This side-effect may be, if necessary, treated with local or oral antihistaminic drugs (e.g., clemastine, or diphenhydramine). Bleeding at injection site, thrombophlebitis at local veins, and (paradoxical) arterial thrombotic events.
- Occasionally deposition of cleaved fibrinogen derivates in the splen resulting in splenomegaly; rupture is possible, if the spleen is palpated too strongly (life-threatening bleeding and need of splenectomy may result).
- Specific side-effects are local and systemic bleeding events. Local bleeding events may be treated with local pressure or surgical dressings, if necessary. Compared with other anticoagulants the risk of systemic bleeding is relatively low. If systemic bleeding is severe enough to warrant fast reversal of ancrod action, fibrinogen should be substituted (please refer to section 'special antidotes').
- Occasionally, increased headache has been found in patients with known migraine.
- Also, chills and fever may occur infrequently.
Thrombocytopenia as side-effect has never been noticed with ancrod in contrast to heparin.
# Availablility
Viprinex® is not currently approved or available. | https://www.wikidoc.org/index.php/Ancrod | |
87a5f3943fc8c39e6f69694e296076513e68da5d | wikidoc | Band 3 | Band 3
Band 3 anion transport protein, also known as anion exchanger 1 (AE1) or band 3 or solute carrier family 4 member 1 (SLC4A1), is a protein that is encoded by the SLC4A1 gene in humans.
Band 3 anion transport protein is a phylogenetically-preserved transport protein responsible for mediating the exchange of chloride (Cl−) with bicarbonate (HCO3−) across plasma membranes. Functionally similar members of the AE clade are AE2 and AE3.
# Function
Band 3 is present in the basolateral face of the α-intercalated cells of the collecting ducts of the nephron, which are the main acid-secreting cells of the kidney. They generate hydrogen ions and bicarbonate ions from carbon dioxide and water – a reaction catalysed by carbonic anhydrase. The hydrogen ions are pumped into the collecting duct tubule by vacuolar H+ ATPase, the apical proton pump, which thus excretes acid into the urine. kAE1 exchanges bicarbonate for chloride on the basolateral surface, essentially returning bicarbonate to the blood. Here it performs two functions:
- Electroneutral chloride and bicarbonate exchange across the plasma membrane on a one-for-one basis. This is crucial for CO2 uptake by the red blood cell and conversion (by hydration catalysed by carbonic anhydrase) into a proton and a bicarbonate ion. The bicarbonate is then excreted (in exchange for a chloride) from the cell by band 3.
- Physical linkage of the plasma membrane to the underlying membrane skeleton (via binding with ankyrin and protein 4.2). This appears to be to prevent membrane surface loss, rather than having to do with membrane skeleton assembly.
# Distribution
It is ubiquitous throughout the vertebrates. In mammals, it is present in two specific sites:
- the erythrocyte (red blood cell) cell membrane and
- the basolateral surface of the alpha-intercalated cell (the acid secreting cell type) in the collecting duct of the kidney.
# Gene products
The erythrocyte and kidney forms are different isoforms of the same protein.
The erythrocyte isoform of AE1, known as eAE1, is composed of 911 amino acids. eAE1 is an important structural component of the erythrocyte cell membrane, making up to 25% of the cell membrane surface. Each red cell contains approximately one million copies of eAE1.
The kidney isoform of AE1, known as kAE1 (which is 65 amino acids shorter than erythroid AE1) is found in the basolateral membrane of alpha-intercalated cells in the cortical collecting duct of the kidney.
# Clinical significance
Mutations of kidney AE1 cause distal (type 1) renal tubular acidosis, which is an inability to acidify the urine, even if the blood is too acidic. These mutations are disease causing as they cause mistargetting of the mutant band 3 proteins so that they are retained within the cell or occasionally addressed to the wrong (i.e. apical) surface.
Mutations of erythroid AE1 affecting the extracellular domains of the molecule may cause alterations in the individual's blood group, as band 3 determines the Diego blood group.
More importantly erythroid AE1 mutations cause 15–25% of cases of Hereditary spherocytosis (a disorder associated with progressive red cell membrane loss), and also cause the hereditary conditions of Hereditary stomatocytosis and Southeast Asian Ovalocytosis
# Interactions
Band 3 has been shown to interact with CA2 and CA4.
# Discovery
AE1 was discovered following SDS-PAGE ( sodium dodecyl sulfate polyacrylamide gel electrophoresis ) of erythrocyte cell membrane. The large 'third' band on the electrophoresis gel represented AE1, which was thus initially termed 'Band 3'. | Band 3
Band 3 anion transport protein, also known as anion exchanger 1 (AE1) or band 3 or solute carrier family 4 member 1 (SLC4A1), is a protein that is encoded by the SLC4A1 gene in humans.
Band 3 anion transport protein is a phylogenetically-preserved transport protein responsible for mediating the exchange of chloride (Cl−) with bicarbonate (HCO3−) across plasma membranes. Functionally similar members of the AE clade are AE2 and AE3.[1]
# Function
Band 3 is present in the basolateral face of the α-intercalated cells of the collecting ducts of the nephron, which are the main acid-secreting cells of the kidney. They generate hydrogen ions and bicarbonate ions from carbon dioxide and water – a reaction catalysed by carbonic anhydrase. The hydrogen ions are pumped into the collecting duct tubule by vacuolar H+ ATPase, the apical proton pump, which thus excretes acid into the urine. kAE1 exchanges bicarbonate for chloride on the basolateral surface, essentially returning bicarbonate to the blood. Here it performs two functions:
- Electroneutral chloride and bicarbonate exchange across the plasma membrane on a one-for-one basis. This is crucial for CO2 uptake by the red blood cell and conversion (by hydration catalysed by carbonic anhydrase) into a proton and a bicarbonate ion. The bicarbonate is then excreted (in exchange for a chloride) from the cell by band 3.
- Physical linkage of the plasma membrane to the underlying membrane skeleton (via binding with ankyrin and protein 4.2). This appears to be to prevent membrane surface loss, rather than having to do with membrane skeleton assembly.
# Distribution
It is ubiquitous throughout the vertebrates. In mammals, it is present in two specific sites:
- the erythrocyte (red blood cell) cell membrane and
- the basolateral surface of the alpha-intercalated cell (the acid secreting cell type) in the collecting duct of the kidney.
# Gene products
The erythrocyte and kidney forms are different isoforms of the same protein.[2]
The erythrocyte isoform of AE1, known as eAE1, is composed of 911 amino acids. eAE1 is an important structural component of the erythrocyte cell membrane, making up to 25% of the cell membrane surface. Each red cell contains approximately one million copies of eAE1.
The kidney isoform of AE1, known as kAE1 (which is 65 amino acids shorter than erythroid AE1) is found in the basolateral membrane of alpha-intercalated cells in the cortical collecting duct of the kidney.
# Clinical significance
Mutations of kidney AE1 cause distal (type 1) renal tubular acidosis, which is an inability to acidify the urine, even if the blood is too acidic. These mutations are disease causing as they cause mistargetting of the mutant band 3 proteins so that they are retained within the cell or occasionally addressed to the wrong (i.e. apical) surface.
Mutations of erythroid AE1 affecting the extracellular domains of the molecule may cause alterations in the individual's blood group, as band 3 determines the Diego blood group.
More importantly erythroid AE1 mutations cause 15–25% of cases of Hereditary spherocytosis (a disorder associated with progressive red cell membrane loss), and also cause the hereditary conditions of Hereditary stomatocytosis[3] and Southeast Asian Ovalocytosis[4]
# Interactions
Band 3 has been shown to interact with CA2[5][6][7][8] and CA4.[9]
# Discovery
AE1 was discovered following SDS-PAGE ( sodium dodecyl sulfate polyacrylamide gel electrophoresis ) of erythrocyte cell membrane. The large 'third' band on the electrophoresis gel represented AE1, which was thus initially termed 'Band 3'. | https://www.wikidoc.org/index.php/Anion_Exchanger_1 | |
368d88979b40031a7bf60f0e0e2e6e656dbfff79 | wikidoc | Anomer | Anomer
In sugar chemistry, an anomer is a special type of epimer. It is a stereoisomer (diastereomer, more exactly) of a saccharide (in the cyclic form) that differs only in its configuration at the hemiacetal (or hemiketal) carbon, also called the anomeric carbon. If the structure is analogous to one with the hydroxyl group on the anomeric carbon in the axial position of glucose, then the sugar is an alpha anomer. If, however, that hydroxyl is equatorial, the sugar is a beta anomer. For example, α-D-glucopyranose and β-D-glucopyranose, the two cyclic forms of glucose, are anomers.
The anomeric effect helps stabilize the α-anomer. The term for interconversion between the two anomers is mutarotation.
The two different anomers are two distinct chemical structures, and thus have different physical and chemical properties, notably optical rotation. For example, α-D-glucose has an optical rotation of +112 degrees and its anomer, β-D-glucose, has an optical rotation of +19 degrees. | Anomer
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
In sugar chemistry, an anomer is a special type of epimer. It is a stereoisomer (diastereomer, more exactly) of a saccharide (in the cyclic form) that differs only in its configuration at the hemiacetal (or hemiketal) carbon, also called the anomeric carbon. If the structure is analogous to one with the hydroxyl group on the anomeric carbon in the axial position of glucose, then the sugar is an alpha anomer. If, however, that hydroxyl is equatorial, the sugar is a beta anomer. For example, α-D-glucopyranose and β-D-glucopyranose, the two cyclic forms of glucose, are anomers.
The anomeric effect helps stabilize the α-anomer. The term for interconversion between the two anomers is mutarotation.
The two different anomers are two distinct chemical structures, and thus have different physical and chemical properties, notably optical rotation. For example, α-D-glucose has an optical rotation of +112 degrees and its anomer, β-D-glucose, has an optical rotation of +19 degrees. | https://www.wikidoc.org/index.php/Anomer | |
c6b142f260f6e4bf67a788ca833759006b5cef5d | wikidoc | Antrum | Antrum
In Biology, "Antrum" is a general term for a cavity or chamber which may have specific meaning in reference to certain organs or sites in the body.
Examples include
- antrum cardiacum - a dilation that occurs in the esophagus near the stomach (forestomach)
- mastoid antrum - Synonym: antrum mastoideum, tympanic antrum, Valsalva's antrum
- pyloric antrum - the initial portion of the pyloric part of the stomach
- antrum follicularum - the cavity in the epithelium that envelops the oocyte
de:Antrum | Antrum
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
In Biology, "Antrum" is a general term for a cavity or chamber which may have specific meaning in reference to certain organs or sites in the body.
Examples include
- antrum cardiacum - a dilation that occurs in the esophagus near the stomach (forestomach)
- mastoid antrum - Synonym: antrum mastoideum, tympanic antrum, Valsalva's antrum
- pyloric antrum - the initial portion of the pyloric part of the stomach
- antrum follicularum - the cavity in the epithelium that envelops the oocyte
de:Antrum
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Antrum | |
458bb29a4c9606a2a01c071c2d94997a213c9539 | wikidoc | Cardia | Cardia
# Overview
The cardia (or esophagogastric junction or gastroesophageal junction ) is the anatomical term for the junction orifice of the stomach and the esophagus. At the cardia, the mucosa of the esophagus transitions into gastric mucosa.
The cardia is also the site of the lower esophageal sphincter (LES) (also termed cardiac sphincter, gastroesophageal sphincter, and esophageal sphincter).
# Nomenclature and classification
There is disagreement in the academic anatomy community over whether the cardia is part of the stomach, part of the esophagus or a distinct entity, as described in this article. The difference is more than semantic when used in clinical studies and applied to individual patients.
Classical anatomy textbooks, and some other resources, describe the cardia as the first of 4 regions of the stomach. This makes sense histologically because the mucosa of the cardia is the same as that of the stomach.
Many recent writings describe it as the LES.
# Function
The stomach generates strong acids and enzymes to aid in food digestion. This digestive mixture is called gastric juice. The inner lining of the stomach has several mechanisms to resist the effect of gastric juice on itself, but the mucosa of the esophagus does not. The esophagus is normally protected from these acids by a one-way valve mechanism at its junction with the stomach. This one-way valve is called the lower esophageal sphincter (LES), and prevents gastric juice from flowing back into the esophagus.
During peristalsis, the LES allows the food bolus to pass into the stomach. It prevents chyme, a mixture of bolus, stomach acid, and digestive enzymes, from returning up the esophagus. The LES is aided in the task of keeping the flow of materials in one direction by the diaphragm.
# Histology
On histological examination, the junction can be identified by the following transition:
- nonkeratinized stratified squamous epithelium in the esophagus
- simple columnar epithelium in the stomach
However, in Barrett's esophagus, the epithelial distinction may vary, so the histological border may not be identical with the functional border.
The cardiac glands can be seen in this region. They can be distinguished from other stomach glands (fundic glands and pyloric glands) because the glands are shallow and simple tubular.
# Pathology
Deficiencies in the strength or the efficiency of the LES lead to various medical problems involving acid damage on the esophagus.
In achalasia, one of the defects is failure of the LES to relax properly.
# Etymology
The word comes from the Greek kardia meaning heart, the cardiac orifice of the stomach.
# Additional images
- Section of mucous membrane of human stomach, near the cardiac orifice. X 45. | Cardia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Template:Infobox Anatomy
The cardia (or esophagogastric junction [1][2] or gastroesophageal junction [3][4][5][6]) is the anatomical term for the junction orifice of the stomach and the esophagus. At the cardia, the mucosa of the esophagus transitions into gastric mucosa.
The cardia is also the site of the lower esophageal sphincter (LES)[7][8][9] (also termed cardiac sphincter[10], gastroesophageal sphincter[11], and esophageal sphincter[12]).
# Nomenclature and classification
There is disagreement in the academic anatomy community over whether the cardia is part of the stomach, part of the esophagus or a distinct entity, as described in this article. The difference is more than semantic when used in clinical studies and applied to individual patients.
Classical anatomy textbooks, and some other resources[13][14], describe the cardia as the first of 4 regions of the stomach. This makes sense histologically because the mucosa of the cardia is the same as that of the stomach.
Many recent writings describe it as the LES.
# Function
The stomach generates strong acids and enzymes to aid in food digestion. This digestive mixture is called gastric juice. The inner lining of the stomach has several mechanisms to resist the effect of gastric juice on itself, but the mucosa of the esophagus does not. The esophagus is normally protected from these acids by a one-way valve mechanism at its junction with the stomach. This one-way valve is called the lower esophageal sphincter (LES), and prevents gastric juice from flowing back into the esophagus.
During peristalsis, the LES allows the food bolus to pass into the stomach. It prevents chyme, a mixture of bolus, stomach acid, and digestive enzymes, from returning up the esophagus. The LES is aided in the task of keeping the flow of materials in one direction by the diaphragm.
# Histology
On histological examination, the junction can be identified by the following transition:[15][16]
- nonkeratinized stratified squamous epithelium in the esophagus
- simple columnar epithelium in the stomach
However, in Barrett's esophagus, the epithelial distinction may vary, so the histological border may not be identical with the functional border.
The cardiac glands can be seen in this region. They can be distinguished from other stomach glands (fundic glands and pyloric glands) because the glands are shallow and simple tubular.
# Pathology
Deficiencies in the strength or the efficiency of the LES lead to various medical problems involving acid damage on the esophagus.
In achalasia, one of the defects is failure of the LES to relax properly.
# Etymology
The word comes from the Greek kardia meaning heart, the cardiac orifice of the stomach.
# Additional images
-
- Section of mucous membrane of human stomach, near the cardiac orifice. X 45. | https://www.wikidoc.org/index.php/Antrum_cardiacum | |
e3860a1c669dd9399611313dc186803a46e8b330 | wikidoc | Anuria | Anuria
To view a comprehensive algorithm of common findings of urine composition and urine output, click here
# Overview
Anuria means nonpassage of urine, in practice is defined as passage of less than 100 milliliters of urine in a day. Anuria is often caused by failure in the function of kidneys. It may also occur because of some severe obstruction like kidney stones or tumours. It may occur with end stage renal disease. It is a more extreme reduction than oliguria, sometimes called anuresis.
# Causes
Failure of kidney function, which can have multiple causes including medications or toxins (e.g., antifreeze, cephalosporins, ACEIs); diabetes; high blood pressure. Stones or tumours in the urinary tract can also cause it by creating an obstruction to urinary flow. High blood calcium, oxalate, or uric acid, can contribute to the risk of stone formation. In males, an enlarged prostate gland is a common cause of obstructive anuria.
Acute anuria, where the decline in urine production occurs quickly, is usually a sign of obstruction or acute renal failure. Acute renal failure can be caused by factors not related to the kidney, such as heart failure, mercury poisoning, infection, and other conditions that cause the kidney to be deprived of blood flow.
# Symptoms
Anuria itself is a symptom, not a disease. It is often associated with other symptoms of kidney failure, such as lack of appetite, weakness, nausea and vomiting. These are mostly the result of buildup of toxins in the blood which would normally be removed by healthy kidneys.
# Treatment
Treatment is dependent on the underlying cause of this symptom. The most easily treatable cause is obstruction of urine flow, which is often solved by insertion of a urinary catheter into the urinary bladder.
Mannitol is a medicine that is used to increase the amount of water removed from the blood and thus improve the blood flow to the kidneys. However, mannitol is contraindicated in anuria secondary to renal disease, severe dehydration, intracranial bleeding (except during craniotomy), severe pulmonary congestion, or pulmonary edema.
Dextrose and Dobutamine are both used to increase blood flow to the kidney and act within 30 to 60 minutes.
Contraindicated medications
- Tromethamine | Anuria
Template:Seealso
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
To view a comprehensive algorithm of common findings of urine composition and urine output, click here
# Overview
Anuria means nonpassage of urine,[1] in practice is defined as passage of less than 100 milliliters of urine in a day.[2] Anuria is often caused by failure in the function of kidneys. It may also occur because of some severe obstruction like kidney stones or tumours. It may occur with end stage renal disease. It is a more extreme reduction than oliguria, sometimes called anuresis.
# Causes
Failure of kidney function, which can have multiple causes including medications or toxins (e.g., antifreeze, cephalosporins, ACEIs); diabetes; high blood pressure. Stones or tumours in the urinary tract can also cause it by creating an obstruction to urinary flow. High blood calcium, oxalate, or uric acid, can contribute to the risk of stone formation. In males, an enlarged prostate gland is a common cause of obstructive anuria.
Acute anuria, where the decline in urine production occurs quickly, is usually a sign of obstruction or acute renal failure. Acute renal failure can be caused by factors not related to the kidney, such as heart failure, mercury poisoning, infection, and other conditions that cause the kidney to be deprived of blood flow.
# Symptoms
Anuria itself is a symptom, not a disease. It is often associated with other symptoms of kidney failure, such as lack of appetite, weakness, nausea and vomiting. These are mostly the result of buildup of toxins in the blood which would normally be removed by healthy kidneys.
# Treatment
Treatment is dependent on the underlying cause of this symptom. The most easily treatable cause is obstruction of urine flow, which is often solved by insertion of a urinary catheter into the urinary bladder.
Mannitol is a medicine that is used to increase the amount of water removed from the blood and thus improve the blood flow to the kidneys. However, mannitol is contraindicated in anuria secondary to renal disease, severe dehydration, intracranial bleeding (except during craniotomy), severe pulmonary congestion, or pulmonary edema.
Dextrose and Dobutamine are both used to increase blood flow to the kidney and act within 30 to 60 minutes.
Contraindicated medications
- Tromethamine | https://www.wikidoc.org/index.php/Anuria | |
d5ffca5575fce051011d9a1d117c0dab10b19dd4 | wikidoc | Apaf-1 | Apaf-1
Apaf-1 (apoptotic protease activating factor 1) is a cytosolic protein involved in cell death or apoptosis. When Cytochrome c is released from the mitochondria, it interacts with Apaf-1 and dATP to form the apoptosome, a large oligomeric protein complex which can activate caspase 9.
The crystal structure of this protein was solved in April of 2005 by the laboratory of Yigong Shi. It contains a Greek Key Motif composed of six helices and 94 amino acids.
The actual mechanism for this reaction is still debated though work published in April of 2006 from the laboratory of Guy Salvesen suggests that the apoptosome may induce caspase 9 dimerization and subsequent autocatalyzation . | Apaf-1
Apaf-1 (apoptotic protease activating factor 1) is a cytosolic protein involved in cell death or apoptosis. When Cytochrome c is released from the mitochondria, it interacts with Apaf-1 and dATP to form the apoptosome, a large oligomeric protein complex which can activate caspase 9.
The crystal structure of this protein was solved in April of 2005 by the laboratory of Yigong Shi[1]. It contains a Greek Key Motif composed of six helices and 94 amino acids.
The actual mechanism for this reaction is still debated though work published in April of 2006 from the laboratory of Guy Salvesen suggests that the apoptosome may induce caspase 9 dimerization and subsequent autocatalyzation [2].
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Apaf-1 | |
719bb8a067b82eec549b451c199e92c124b0e5c6 | wikidoc | Apamin | Apamin
Apamin is a neurotoxin which selectively blocks SK channels, a type of Ca2+-activated K+ channels expressed in the central nervous system. The final 18 amino acid polypeptide is a component of apitoxin (bee venom). It is used primarily in biomedical research to study the electrical properties of SK channels and their role in the afterhyperpolarizations occurring immediately following an action potential.
# Origin
Apamin is a neurotoxin that was originally isolated from Apis mellifera, the Western honey bee. The venom of the honeybee consists of many more products, like melittin, the MCD peptide and phospholipase A2.
# Chemistry
Apamin is a polypeptide possessing an amino acid sequence of C00H-Cys-Asn-Cys-Lys-Ala-Pro-Glu-Thr-Ala-Leu-Cys-Ala-Arg-Arg-Cys-Gln-Gln-His-NH2 (with disulfide bonds between Cys1-Cys11 and Cys3-Cys15). Because honeybee venom is a complex mixture of short peptides and proteins, it is difficult to isolate apamin. The isolation can be done by electrophoresis, or by chromatography.
# Pharmacology
Apamin binds to the SK channels (small conductance Ca2+-activated K+ channels) in the brain and spinal cord and inhibits them. It inhibits the three cloned SK channel subtypes (SK1, SK2, and SK3) with different affinity, highest affinity for SK2, lowest for SK1, and intermediate for SK3 channels. Heteromers show intermediate sensitivity. Most likely, apamin acts as a pore blocker, although residues both inside and outside of the pore region of the SK channels participate in apamin binding.
The SK channels are present in a wide range of excitable and non-excitable cells, including cells in the central nervous system, intestinal myocytes, endothelial cells, and hepatocytes.
SK channels, when activated, contribute to afterhyperpolarizations in neurons, which control neuronal excitability. Intracellular Ca2+ binding to calmodulin can activate these channels. Channel deactivation can take place through dissociation of Ca2+ from calmodulin. Inhibition of SK channels by apamin will increase the neuronal excitability and lower the threshold for generating an action potential.
Other toxins that block SK channels are tamapin and scyllatoxin.
# Toxicity
Symptoms following bee sting or apamin poisoning may include:
- local effects: burning or stinging pain, swelling, redness.
- severe systemic reactions: swelling of the tongue and throat, difficulty breathing, and shock.
- development of optic neuritis and atrophy.
- atrial fibrillation, cerebral infarction, acute myocardial infarction, Fisher's syndrome, acute inflammatory polyradiculopathy (Guillain-Barre syndrome), claw hand (through a central action of apamin on the spinal cord and a peripheral action in the form of median and ulnar neuritis, causing spasms of the long flexors in the forearm).
- dramatic haemorrhagic effect in the lungs.
Patients poisoned with bee venom can be treated with anti-inflammatory medication, antihistamines and oral prednisolone.
# Therapeutic Use
SK channel blockers such as apamin can have therapeutic applications, for example on the peripheral cells (e.g. the insulin releasing cells of the pancreas) and on the central nervous system where there is evidence for a role of SK channels in memory processes, both general and specifically hippocampal.
SK channels have been proposed as targets for the treatment of ataxia, epilepsy, memory disorders, and possibly schizophrenia and Parkinson's disease. | Apamin
Template:Protbox
Template:Chembox new
Apamin is a neurotoxin which selectively blocks SK channels, a type of Ca2+-activated K+ channels expressed in the central nervous system. The final 18 amino acid polypeptide is a component of apitoxin (bee venom).[1] It is used primarily in biomedical research to study the electrical properties of SK channels and their role in the afterhyperpolarizations occurring immediately following an action potential.[2]
# Origin
Apamin is a neurotoxin that was originally isolated from Apis mellifera, the Western honey bee. The venom of the honeybee consists of many more products, like melittin, the MCD peptide and phospholipase A2.
# Chemistry
Apamin is a polypeptide possessing an amino acid sequence of C00H-Cys-Asn-Cys-Lys-Ala-Pro-Glu-Thr-Ala-Leu-Cys-Ala-Arg-Arg-Cys-Gln-Gln-His-NH2 (with disulfide bonds between Cys1-Cys11 and Cys3-Cys15). Because honeybee venom is a complex mixture of short peptides and proteins, it is difficult to isolate apamin. The isolation can be done by electrophoresis,[3] or by chromatography.[4][5]
# Pharmacology
Apamin binds to the SK channels (small conductance Ca2+-activated K+ channels) in the brain and spinal cord and inhibits them.[6] It inhibits the three cloned SK channel subtypes (SK1, SK2, and SK3) with different affinity, highest affinity for SK2, lowest for SK1, and intermediate for SK3 channels. Heteromers show intermediate sensitivity. Most likely, apamin acts as a pore blocker, although residues both inside and outside of the pore region of the SK channels participate in apamin binding.[7]
The SK channels are present in a wide range of excitable and non-excitable cells, including cells in the central nervous system, intestinal myocytes, endothelial cells, and hepatocytes.
SK channels, when activated, contribute to afterhyperpolarizations in neurons, which control neuronal excitability. Intracellular Ca2+ binding to calmodulin can activate these channels. Channel deactivation can take place through dissociation of Ca2+ from calmodulin.[8] Inhibition of SK channels by apamin will increase the neuronal excitability and lower the threshold for generating an action potential.
Other toxins that block SK channels are tamapin and scyllatoxin.
# Toxicity
Symptoms following bee sting or apamin poisoning may include:
- local effects: burning or stinging pain, swelling, redness.
- severe systemic reactions: swelling of the tongue and throat, difficulty breathing, and shock.
- development of optic neuritis and atrophy.
- atrial fibrillation, cerebral infarction, acute myocardial infarction, Fisher's syndrome, acute inflammatory polyradiculopathy (Guillain-Barre syndrome), claw hand (through a central action of apamin on the spinal cord and a peripheral action in the form of median and ulnar neuritis, causing spasms of the long flexors in the forearm).[9]
- dramatic haemorrhagic effect in the lungs.[10]
Patients poisoned with bee venom can be treated with anti-inflammatory medication, antihistamines and oral prednisolone.[9]
# Therapeutic Use
SK channel blockers such as apamin can have therapeutic applications, for example on the peripheral cells (e.g. the insulin releasing cells of the pancreas) and on the central nervous system where there is evidence for a role of SK channels in memory processes, both general and specifically hippocampal.[8]
SK channels have been proposed as targets for the treatment of ataxia, epilepsy, memory disorders, and possibly schizophrenia and Parkinson's disease. | https://www.wikidoc.org/index.php/Apamin | |
555473971a499ac3188f7614d63e64c0f11b222e | wikidoc | Apathy | Apathy
# Background
Apathy is a psychological term for a state of indifference — where an individual is unresponsive or "indifferent" to aspects of emotional, social, or physical life. Clinical apathy is considered to be at an elevated level, while a moderate level might be considered depression, and an extreme level could be diagnosed as a dissociative disorder. The physical aspect of apathy associated with physical deterioration, muscle loss, and lack of energy is called lethargy — which has many pathological causes as well.
Apathy can be object-specific — toward a person, activity or environment. It is a common reaction to stress where it manifests as "learned helplessness" and is commonly associated with depression. It can also reflect a non-pathological lack of interest in things one does not consider important.
# History
Apathy is a common feeling of complete discontent for one's emotional behaviour.
Apathy etymologically derives from the Greek απάθεια (apatheia), a term used by the Stoics to signify indifference for what one is not responsible for (that is, according to their philosophy, all things exterior, one being only responsible of his representations and judgments). The concept was then reappropriated by Christians, who adopted the term to express a contempt of all earthly concerns, a state of mortification, as the gospel prescribes. Thus, the word has been used since then among more devout writers. Clemens Alexandrinus, in particular, brought the term exceedingly in vogue, thinking hereby to draw the philosophers to Christianity, who aspired after such a sublime pitch of virtue. Template:Ref label
The concept of apathy became more sympathetically accepted in popular culture during the First World War, in which the appalling conditions of the Western Front led to apathy and shellshock amongst millions of soldiers. | Apathy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Background
Apathy is a psychological term for a state of indifference — where an individual is unresponsive or "indifferent" to aspects of emotional, social, or physical life. Clinical apathy is considered to be at an elevated level, while a moderate level might be considered depression, and an extreme level could be diagnosed as a dissociative disorder. The physical aspect of apathy associated with physical deterioration, muscle loss, and lack of energy is called lethargy — which has many pathological causes as well.
Apathy can be object-specific — toward a person, activity or environment. It is a common reaction to stress where it manifests as "learned helplessness" and is commonly associated with depression. It can also reflect a non-pathological lack of interest in things one does not consider important.
# History
Apathy is a common feeling of complete discontent for one's emotional behaviour.
Apathy etymologically derives from the Greek απάθεια (apatheia), a term used by the Stoics to signify indifference for what one is not responsible for (that is, according to their philosophy, all things exterior, one being only responsible of his representations and judgments). The concept was then reappropriated by Christians, who adopted the term to express a contempt of all earthly concerns, a state of mortification, as the gospel prescribes. Thus, the word has been used since then among more devout writers. Clemens Alexandrinus, in particular, brought the term exceedingly in vogue, thinking hereby to draw the philosophers to Christianity, who aspired after such a sublime pitch of virtue. Template:Ref label
The concept of apathy became more sympathetically accepted in popular culture during the First World War, in which the appalling conditions of the Western Front led to apathy[citation needed] and shellshock amongst millions of soldiers. | https://www.wikidoc.org/index.php/Apathy | |
29cd3ec698107d8fbe68b01483f8e2bc43a49ef6 | wikidoc | Apelin | Apelin
Apelin (also known as APLN) is a peptide that in humans is encoded by the APLN gene. Apelin is the endogenous ligand for the G-protein-coupled APJ receptor that is expressed at the surface of some cell types. It is widely expressed in various organs such as the heart, lung, kidney, liver, adipose tissue, gastrointestinal tract, brain, adrenal glands, endothelium, and human plasma.
# Discovery
Apelin is a peptide that was identified in 1998 by Professor M. Fujino’s team.
# Biosynthesis
Apelin gene encodes a pre-proprotein of 77 amino acids, with a signal peptide in the N-terminal region. After translocation into the endoplasmic reticulum and cleavage of the signal peptide, the proprotein of 55 amino acids may generate several active fragments: a 36 amino acid peptide corresponding to the sequence 42-77 (apelin 36), a 17 amino acid peptide corresponding to the sequence 61-77 (apelin 17) and a 13 amino acid peptide corresponding to the sequence 65-77 (apelin 13). This latter fragment may also undergo a pyroglutamylation at the level of its N-terminal glutamine residue. However the presence and/or the concentrations of those peptides in human plasma has been questioned. Recently, 46 different apelin peptides ranging from apelin 55 (proapelin) to apelin 12 have been identified in bovine colostrum, including C-ter truncated isoforms.
# Physiological functions
The sites of receptor expression are clearly linked to the different functions played by apelin in the organism.
## Vascular
Vascular expression of the receptor participates in the control of blood pressure and its activation promotes the formation of new blood vessels (angiogenesis). The hypotensive effect of apelin results from the activation of receptors expressed at the surface of endothelial cells. This activation induces the release of NO, a potent vasodilator, which induces relaxation of the smooth muscle cells of artery wall. Studies performed on mice knocked out for the apelin receptor gene have suggested the existence of a balance between angiotensin II signalling, which increases blood pressure and apelin signalling, which lowers blood pressure. The angiogenic activity is the consequence of apelin action on the proliferation and migration of the endothelial cells. Apelin activates inside the cell transduction cascades (ERKs, Akt, and p70S6kinase phosphorylation), which lead to the proliferation of endothelial cells and the formation of new blood vessels. Knockout of the apelin gene is associated with a delay in the development of the retinal vasculature.
## Cardiac
The apelin receptor is expressed early during the embryonic development of the heart, where it regulates the migration of cell progenitors fated to differentiate into cardiomyocytes, the contractile cells of the heart. Its expression is also detected in the cardiomyocytes of the adult where apelin behaves as one of the most potent stimulator of cardiac contractility. Aged apelin knockout mice develop progressive impairment of cardiac contractility. Apelin acts as a mediator of the cardiovascular control, including for blood pressure and blood flow. It is one of the most potent stimulators of cardiac contractility yet identified, and plays a role in cardiac tissue remodeling. Apelin levels are increased in left ventricles of patients with chronic heart failure and also in patients with chronic liver disease.
## Exercise
The plasma concentration of apelin is shown to increase during exercise.. Paradoxically,exogenous apelin in healthy volunteers reduced peak VO2 in an endurance test.
## Brain
Apelin receptor is also expressed in the neurons of brain areas involved in regulating water and food intake. Apelin injection increases water intake and apelin decreases the hypothalamic secretion of the antidiuretic hormone vasopressin. This diuretic effect of apelin in association with its hypotensive effect participates in the homeostatic regulation of body fluid. Apelin is also detected in brain areas which control appetite, but its effects on food intake are very contradictory.
## Adipose tissue
Apelin is expressed and secreted by adipocytes, and its production is increased during adipocyte differentiation and is stimulated by insulin. Most obese people have elevated levels of insulin, which may therefore be the reason why obese people have been reported to also have elevated levels of apelin.
## Digestive
Apelin receptor is expressed in several cell types of the gastro-intestinal tract : stomach enterochromaffine-like cells; unknown cells of endocrine pancreas, colon epithelial cells.
In stomach, activation of receptors on enterochromaffine-like cells by apelin secreted by parietal cells can inhibit histamine release by enterochromaffine-like cells, which in turn decreases acid secretion by parietal cells. In pancreas, apelin inhibits the insulin secretion induced by glucose. This inhibition reveals the functional interdependency between apelin signalling and insulin signalling observed at the adipocyte level where insulin stimulate apelin production. Recently, receptor expression was also detected in skeletic muscle cells. Its activation is involved in glucose uptake and participates in the control of glucose blood levels glycemia.
## Bone
Receptor expression is also observed at the surface of osteoblasts, the cell progenitors involved in bone formation.
## Muscle aging
Muscle apelin expression decreases with age in rodents and humans. By supplementing aged mice with exogenous apelin, the team of Dr C. Dray shown that the peptide was able to promote muscle hypertrophy and consequently induced a gain in strength. This study also demonstrated that apelin targets muscle cells during aging by different and complementary pathways: it acts on muscle metabolism by activating an AMPK-dependent mitochondria biogenesis, it promotes autophagy and decreases inflammation in aged mice. Moreover, apelin receptor is also present on muscle stem cells and promotes in vitro and in vivo proliferation and differenciation of these cells into mature muscle cells participating to muscle regeneration. Finally, muscle apelin could be used a biomarker of physical exercise success in aged individual since its production is corelated to the benefit of a chronic physical exercise in aged individuals. | Apelin
Apelin (also known as APLN) is a peptide that in humans is encoded by the APLN gene.[1] Apelin is the endogenous ligand for the G-protein-coupled APJ receptor[2][3][4][5][6] that is expressed at the surface of some cell types.[7] It is widely expressed in various organs such as the heart, lung, kidney, liver, adipose tissue, gastrointestinal tract, brain, adrenal glands, endothelium, and human plasma.
# Discovery
Apelin is a peptide that was identified in 1998 by Professor M. Fujino’s team.[1]
# Biosynthesis
Apelin gene encodes a pre-proprotein of 77 amino acids,[1] with a signal peptide in the N-terminal region. After translocation into the endoplasmic reticulum and cleavage of the signal peptide, the proprotein of 55 amino acids may generate several active fragments: a 36 amino acid peptide corresponding to the sequence 42-77 (apelin 36), a 17 amino acid peptide corresponding to the sequence 61-77 (apelin 17) and a 13 amino acid peptide corresponding to the sequence 65-77 (apelin 13). This latter fragment may also undergo a pyroglutamylation at the level of its N-terminal glutamine residue. However the presence and/or the concentrations of those peptides in human plasma has been questioned.[8] Recently, 46 different apelin peptides ranging from apelin 55 (proapelin) to apelin 12 have been identified in bovine colostrum, including C-ter truncated isoforms.[9]
# Physiological functions
The sites of receptor expression are clearly linked to the different functions played by apelin in the organism.
## Vascular
Vascular expression of the receptor[10][11] participates in the control of blood pressure[2] and its activation promotes the formation of new blood vessels (angiogenesis).[11][12][13][14] The hypotensive effect of apelin results from the activation of receptors expressed at the surface of endothelial cells.[10][11] This activation induces the release of NO,[15] a potent vasodilator, which induces relaxation of the smooth muscle cells of artery wall. Studies performed on mice knocked out for the apelin receptor gene[16] have suggested the existence of a balance between angiotensin II signalling, which increases blood pressure and apelin signalling, which lowers blood pressure. The angiogenic activity is the consequence of apelin action on the proliferation and migration of the endothelial cells. Apelin activates inside the cell transduction cascades (ERKs, Akt, and p70S6kinase phosphorylation),[12][17] which lead to the proliferation of endothelial cells and the formation of new blood vessels.[13] Knockout of the apelin gene is associated with a delay in the development of the retinal vasculature.[18]
## Cardiac
The apelin receptor is expressed early during the embryonic development of the heart, where it regulates the migration of cell progenitors fated to differentiate into cardiomyocytes, the contractile cells of the heart.[19][20] Its expression is also detected in the cardiomyocytes of the adult where apelin behaves as one of the most potent stimulator of cardiac contractility.[3][21][22] Aged apelin knockout mice develop progressive impairment of cardiac contractility.[23] Apelin acts as a mediator of the cardiovascular control, including for blood pressure and blood flow. It is one of the most potent stimulators of cardiac contractility yet identified, and plays a role in cardiac tissue remodeling. Apelin levels are increased in left ventricles of patients with chronic heart failure and also in patients with chronic liver disease.[24]
## Exercise
The plasma concentration of apelin is shown to increase during exercise.[25]. Paradoxically,exogenous apelin in healthy volunteers reduced peak VO2 in an endurance test.[26]
## Brain
Apelin receptor is also expressed in the neurons of brain areas involved in regulating water and food intake.[2][27][28] Apelin injection increases water intake[2] and apelin decreases the hypothalamic secretion of the antidiuretic hormone vasopressin.[29] This diuretic effect of apelin in association with its hypotensive effect participates in the homeostatic regulation of body fluid. Apelin is also detected in brain areas which control appetite, but its effects on food intake are very contradictory.[30][31][32]
## Adipose tissue
Apelin is expressed and secreted by adipocytes, and its production is increased during adipocyte differentiation and is stimulated by insulin.[33] Most obese people have elevated levels of insulin, which may therefore be the reason why obese people have been reported to also have elevated levels of apelin.[33]
## Digestive
Apelin receptor is expressed in several cell types of the gastro-intestinal tract : stomach enterochromaffine-like cells;[34][35] unknown cells of endocrine pancreas,[36] colon epithelial cells.[37]
In stomach, activation of receptors on enterochromaffine-like cells by apelin secreted by parietal cells can inhibit histamine release by enterochromaffine-like cells, which in turn decreases acid secretion by parietal cells.[35] In pancreas, apelin inhibits the insulin secretion induced by glucose.[38] This inhibition reveals the functional interdependency between apelin signalling and insulin signalling observed at the adipocyte level where insulin stimulate apelin production.[33] Recently, receptor expression was also detected in skeletic muscle cells. Its activation is involved in glucose uptake and participates in the control of glucose blood levels glycemia.[39]
## Bone
Receptor expression is also observed at the surface of osteoblasts, the cell progenitors involved in bone formation.[40]
## Muscle aging
Muscle apelin expression decreases with age in rodents and humans[41]. By supplementing aged mice with exogenous apelin, the team of Dr C. Dray shown that the peptide was able to promote muscle hypertrophy and consequently induced a gain in strength[41]. This study also demonstrated that apelin targets muscle cells during aging by different and complementary pathways: it acts on muscle metabolism by activating an AMPK-dependent mitochondria biogenesis, it promotes autophagy and decreases inflammation in aged mice[41]. Moreover, apelin receptor is also present on muscle stem cells and promotes in vitro and in vivo proliferation and differenciation of these cells into mature muscle cells participating to muscle regeneration. Finally, muscle apelin could be used a biomarker of physical exercise success in aged individual since its production is corelated to the benefit of a chronic physical exercise in aged individuals[41]. | https://www.wikidoc.org/index.php/Apelin | |
e61fa40bfdcec7ab8c4eba54f2082aafd6b1bb3f | wikidoc | Enzyme | Enzyme
# Overview
Enzymes are biomolecules that catalyze (i.e. increase the rates of) chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, the products. Almost all processes in a biological cell need enzymes in order to occur at significant rates. Since enzymes are extremely selective for their substrates and speed up only a few reactions from among many possibilities, the set of enzymes made in a cell determines which metabolic pathways occur in that cell.
Like all catalysts, enzymes work by lowering the activation energy (Ea or ΔG‡) for a reaction, thus dramatically increasing the rate of the reaction. Most enzyme reaction rates are millions of times faster than those of comparable uncatalyzed reactions. As with all catalysts, enzymes are not consumed by the reactions they catalyze, nor do they alter the equilibrium of these reactions. However, enzymes do differ from most other catalysts by being much more specific. Enzymes are known to catalyze about 4,000 biochemical reactions. A few RNA molecules called ribozymes catalyze reactions, with an important example being some parts of the ribosome. Synthetic molecules called artificial enzymes also display enzyme-like catalysis.
Enzyme activity can be affected by other molecules. Inhibitors are molecules that decrease enzyme activity; activators are molecules that increase activity. Many drugs and poisons are enzyme inhibitors. Activity is also affected by temperature, chemical environment (e.g. pH), and the concentration of substrate. Some enzymes are used commercially, for example, in the synthesis of antibiotics. In addition, some household products use enzymes to speed up biochemical reactions (e.g., enzymes in biological washing powders break down protein or fat stains on clothes; enzymes in meat tenderizers break down proteins, making the meat easier to chew).
# Etymology and history
As early as the late 1700s and early 1800s, the digestion of meat by stomach secretions and the conversion of starch to sugars by plant extracts and saliva were known. However, the mechanism by which this occurred had not been identified.
In the 19th century, when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur came to the conclusion that this fermentation was catalyzed by a vital force contained within the yeast cells called "ferments", which were thought to function only within living organisms. He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells."
In 1878 German physiologist Wilhelm Kühne (1837–1900) first used the term enzyme, which comes from Greek ενζυμον "in leaven", to describe this process. The word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment used to refer to chemical activity produced by living organisms.
In 1897 Eduard Buchner began to study the ability of yeast extracts that lacked any living yeast cells to ferment sugar. In a series of experiments at the University of Berlin, he found that the sugar was fermented even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose "zymase". In 1907 he received the Nobel Prize in Chemistry "for his biochemical research and his discovery of cell-free fermentation". Following Buchner's example; enzymes are usually named according to the reaction they carry out. Typically the suffix -ase is added to the name of the substrate (e.g., lactase is the enzyme that cleaves lactose) or the type of reaction (e.g., DNA polymerase forms DNA polymers).
Having shown that enzymes could function outside a living cell, the next step was to determine their biochemical nature. Many early workers noted that enzymatic activity was associated with proteins, but several scientists (such as Nobel laureate Richard Willstätter) argued that proteins were merely carriers for the true enzymes and that proteins per se were incapable of catalysis. However, in 1926, James B. Sumner showed that the enzyme urease was a pure protein and crystallized it; Sumner did likewise for the enzyme catalase in 1937. The conclusion that pure proteins can be enzymes was definitively proved by Northrop and Stanley, who worked on the digestive enzymes pepsin (1930), trypsin and chymotrypsin. These three scientists were awarded the 1946 Nobel Prize in Chemistry.
This discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This was first done for lysozyme, an enzyme found in tears, saliva and egg whites that digests the coating of some bacteria; the structure was solved by a group led by David Chilton Phillips and published in 1965. This high-resolution structure of lysozyme marked the beginning of the field of structural biology and the effort to understand how enzymes work at an atomic level of detail.
# Structures and mechanisms
Enzymes are generally globular proteins and range from just 62 amino acid residues in size, for the monomer of 4-oxalocrotonate tautomerase, to over 2,500 residues in the animal fatty acid synthase. A small number of RNA-based biological catalysts exist, with the most common being the ribosome, these are either referred to as RNA-enzymes, or ribozymes. The activities of enzymes are determined by their three-dimensional structure. Most enzymes are much larger than the substrates they act on, and only a small portion of the enzyme (around 3–4 amino acids) is directly involved in catalysis. The region that contains these catalytic residues, binds the substrate, and then carries out the reaction is known as the active site. Enzymes can also contain sites that bind cofactors, which are needed for catalysis. Some enzymes also have binding sites for small molecules, which are often direct or indirect products or substrates of the reaction catalyzed. This binding can serve to increase or decrease the enzyme's activity, providing a means for feedback regulation.
Like all proteins, enzymes are made as long, linear chains of amino acids that fold to produce a three-dimensional product. Each unique amino acid sequence produces a specific structure, which has unique properties. Individual protein chains may sometimes group together to form a protein complex. Most enzymes can be denatured—that is, unfolded and inactivated—by heating or chemical denaturants, which disrupt the three-dimensional structure of the protein. Depending on the enzyme, denaturation may be reversible or irreversible.
## Specificity
Enzymes are usually very specific as to which reactions they catalyze and the substrates that are involved in these reactions. Complementary shape, charge and hydrophilic/hydrophobic characteristics of enzymes and substrates are responsible for this specificity. Enzymes can also show impressive levels of stereospecificity, regioselectivity and chemoselectivity.
Some of the enzymes showing the highest specificity and accuracy are involved in the copying and expression of the genome. These enzymes have "proof-reading" mechanisms. Here, an enzyme such as DNA polymerase catalyzes a reaction in a first step and then checks that the product is correct in a second step. This two-step process results in average error rates of less than 1 error in 100 million reactions in high-fidelity mammalian polymerases. Similar proofreading mechanisms are also found in RNA polymerase, aminoacyl tRNA synthetases and ribosomes.
Some enzymes that produce secondary metabolites are described as promiscuous, as they can act on a relatively broad range of different substrates. It has been suggested that this broad substrate specificity is important for the evolution of new biosynthetic pathways.
### "Lock and key" model
Enzymes are very specific, and it was suggested by Emil Fischer in 1894 that this was because both the enzyme and the substrate possess specific complementary geometric shapes that fit exactly into one another. This is often referred to as "the lock and key" model. However, while this model explains enzyme specificity, it fails to explain the stabilization of the transition state that enzymes achieve.
The "lock and key" model has proven inaccurate and the induced fit model is the most currently accepted enzyme-substrate-coenzyme figure.
### Induced fit model
In 1958 Daniel Koshland suggested a modification to the lock and key model: since enzymes are rather flexible structures, the active site is continually reshaped by interactions with the substrate as the substrate interacts with the enzyme. As a result, the substrate does not simply bind to a rigid active site, the amino acid side chains which make up the active site are moulded into the precise positions that enable the enzyme to perform its catalytic function. In some cases, such as glycosidases, the substrate molecule also changes shape slightly as it enters the active site. The active site continues to change until the substrate is completely bound, at which point the final shape and charge is determined.
## Mechanisms
Enzymes can act in several ways, all of which lower ΔG‡:
- Lowering the activation energy by creating an environment in which the transition state is stabilized (e.g. straining the shape of a substrate - by binding the transition-state conformation of the substrate/product molecules, the enzyme distorts the bound substrate(s) into their transition state form, thereby reducing the amount of energy required to complete the transition).
- Lowering the energy of the transition state, but without distorting the substrate, by creating an environment with the opposite charge distribution to that of the transition state.
- Providing an alternative pathway. For example, temporarily reacting with the substrate to form an intermediate ES complex, which would be impossible in the absence of the enzyme.
- Reducing the reaction entropy change by bringing substrates together in the correct orientation to react. Considering ΔH‡ alone overlooks this effect.
Interestingly, this entropic effect involves destabilization of the ground state, and its contribution to catalysis is relatively small.
### Transition State Stabilization
The understanding of the origin of the reduction of ΔG‡ requires one to find out how the enzymes can stabilize its transition state more than the transition state of the uncatalyzed reaction. Apparently, the most effective way for reaching large stabilization is the use of electrostatic effects, in particular, by having a relatively fixed polar environment that is oriented toward the charge distribution of the transition state. Such an environment does not exist in the uncatalyzed reaction in water.
### Dynamics and function
Recent investigations have provided new insights into the connection between internal dynamics of enzymes and their mechanism of catalysis.
An enzyme's internal dynamics are the movement of its internal parts (e.g. amino acids, a group of amino acids, a loop region, an alpha helix, neighboring beta-sheets or even an entire domain) of these proteins. These movements occur at various time-scales ranging from femtoseconds to seconds. Networks of protein residues throughout an enzyme's structure can contribute to catalysis through dynamic motions. Protein motions are vital to many enzymes, but whether small and fast vibrations, or larger and slower conformational movements are more important depends on the type of reaction involved. However, although these movements are important in binding and releasing substrates and products, it is not clear if protein movements help to accelerate the chemical steps in enzymatic reactions. These new insights also have implications in understanding allosteric effects and developing new drugs.
## Allosteric modulation
Allosteric enzymes change their structure in response to binding of effectors. Modulation can be direct, where the effector binds directly to binding sites in the enzyme, or indirect, where the effector binds to other proteins or protein subunits that interact with the allosteric enzyme and thus influence catalytic activity.
# Cofactors and coenzymes
## Cofactors
Some enzymes do not need any additional components to show full activity. However, others require non-protein molecules called cofactors to be bound for activity. Cofactors can be either inorganic (e.g., metal ions and iron-sulfur clusters) or organic compounds, (e.g., flavin and heme). Organic cofactors can be either prosthetic groups, which are tightly bound to an enzyme, or coenzymes, which are released from the enzyme's active site during the reaction. Coenzymes include NADH, NADPH and adenosine triphosphate. These molecules act to transfer chemical groups between enzymes.
An example of an enzyme that contains a cofactor is carbonic anhydrase, and is shown in the ribbon diagram above with a zinc cofactor bound as part of its active site. These tightly-bound molecules are usually found in the active site and are involved in catalysis. For example, flavin and heme cofactors are often involved in redox reactions.
Enzymes that require a cofactor but do not have one bound are called apoenzymes or apoproteins. An apoenzyme together with its cofactor(s) is called a holoenzyme (this is the active form). Most cofactors are not covalently attached to an enzyme, but are very tightly bound. However, organic prosthetic groups can be covalently bound (e.g., thiamine pyrophosphate in the enzyme pyruvate dehydrogenase).
## Coenzymes
Coenzymes are small organic molecules that transport chemical groups from one enzyme to another. Some of these chemicals such as riboflavin, thiamine and folic acid are vitamins, this is when these compounds cannot be made in the body and must be acquired from the diet. The chemical groups carried include the hydride ion (H-) carried by NAD or NADP+, the acetyl group carried by coenzyme A, formyl, methenyl or methyl groups carried by folic acid and the methyl group carried by S-adenosylmethionine.
Since coenzymes are chemically changed as a consequence of enzyme action, it is useful to consider coenzymes to be a special class of substrates, or second substrates, which are common to many different enzymes. For example, about 700 enzymes are known to use the coenzyme NADH.
Coenzymes are usually regenerated and their concentrations maintained at a steady level inside the cell: for example, NADPH is regenerated through the pentose phosphate pathway and S-adenosylmethionine by methionine adenosyltransferase.
# Thermodynamics
As all catalysts, enzymes do not alter the position of the chemical equilibrium of the reaction. Usually, in the presence of an enzyme, the reaction runs in the same direction as it would without the enzyme, just more quickly. However, in the absence of the enzyme, other possible uncatalyzed, "spontaneous" reactions might lead to different products, because in those conditions this different product is formed faster.
Furthermore, enzymes can couple two or more reactions, so that a thermodynamically favorable reaction can be used to "drive" a thermodynamically unfavorable one. For example, the hydrolysis of ATP is often used to drive other chemical reactions.
Enzymes catalyze the forward and backward reactions equally. They do not alter the equilibrium itself, but only the speed at which it is reached. For example, carbonic anhydrase catalyzes its reaction in either direction depending on the concentration of its reactants.
H_2CO_3} (in tissues; high CO2 concentration)
CO_2 + H_2O} (in lungs; low CO2 concentration)
Nevertheless, if the equilibrium is greatly displaced in one direction, that is, in a very exergonic reaction, the reaction is effectively irreversible. Under these conditions the enzyme will, in fact, only catalyze the reaction in the thermodynamically allowed direction.
# Kinetics
Enzyme kinetics is the investigation of how enzymes bind substrates and turn them into products. The rate data used in kinetic analyses are obtained from enzyme assays.
In 1902 Victor Henri proposed a quantitative theory of enzyme kinetics, but his experimental data were not useful because the significance of the hydrogen ion concentration was not yet appreciated. After Peter Lauritz Sørensen had defined the logarithmic pH-scale and introduced the concept of buffering in 1909 the German chemist Leonor Michaelis and his Canadian postdoc Maud Leonora Menten repeated Henri's experiments and confirmed his equation which is referred to as Henri-Michaelis-Menten kinetics (sometimes also Michaelis-Menten kinetics). Their work was further developed by G. E. Briggs and J. B. S. Haldane, who derived kinetic equations that are still widely used today.
The major contribution of Henri was to think of enzyme reactions in two stages. In the first, the substrate binds reversibly to the enzyme, forming the enzyme-substrate complex. This is sometimes called the Michaelis complex. The enzyme then catalyzes the chemical step in the reaction and releases the product.
File:Michaelis-Menten saturation curve of an enzyme reaction.svg
Enzymes can catalyze up to several million reactions per second. For example, the reaction catalyzed by orotidine 5'-phosphate decarboxylase will consume half of its substrate in 78 million years if no enzyme is present. However, when the decarboxylase is added, the same process takes just 25 milliseconds. Enzyme rates depend on solution conditions and substrate concentration. Conditions that denature the protein abolish enzyme activity, such as high temperatures, extremes of pH or high salt concentrations, while raising substrate concentration tends to increase activity. To find the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation is seen. This is shown in the saturation curve on the right. Saturation happens because, as substrate concentration increases, more and more of the free enzyme is converted into the substrate-bound ES form. At the maximum velocity (Vmax) of the enzyme, all the enzyme active sites are bound to substrate, and the amount of ES complex is the same as the total amount of enzyme.
However, Vmax is only one kinetic constant of enzymes. The amount of substrate needed to achieve a given rate of reaction is also important. This is given by the Michaelis-Menten constant (Km), which is the substrate concentration required for an enzyme to reach one-half its maximum velocity. Each enzyme has a characteristic Km for a given substrate, and this can show how tight the binding of the substrate is to the enzyme. Another useful constant is kcat, which is the number of substrate molecules handled by one active site per second.
The efficiency of an enzyme can be expressed in terms of kcat/Km. This is also called the specificity constant and incorporates the rate constants for all steps in the reaction. Because the specificity constant reflects both affinity and catalytic ability, it is useful for comparing different enzymes against each other, or the same enzyme with different substrates. The theoretical maximum for the specificity constant is called the diffusion limit and is about 108 to 109 (M-1 s-1). At this point every collision of the enzyme with its substrate will result in catalysis, and the rate of product formation is not limited by the reaction rate but by the diffusion rate. Enzymes with this property are called catalytically perfect or kinetically perfect. Example of such enzymes are triose-phosphate isomerase, carbonic anhydrase, acetylcholinesterase, catalase, fumarase, β-lactamase, and superoxide dismutase.
Michaelis-Menten kinetics relies on the law of mass action, which is derived from the assumptions of free diffusion and thermodynamically-driven random collision. However, many biochemical or cellular processes deviate significantly from these conditions, because of very high concentrations, phase-separation of the enzyme/substrate/product, or one or two-dimensional molecular movement. In these situations, a fractal Michaelis-Menten kinetics may be applied.
Some enzymes operate with kinetics which are faster than diffusion rates, which would seem to be impossible. Several mechanisms have been invoked to explain this phenomenon. Some proteins are believed to accelerate catalysis by drawing their substrate in and pre-orienting them by using dipolar electric fields. Other models invoke a quantum-mechanical tunneling explanation, whereby a proton or an electron can tunnel through activation barriers, although for proton tunneling this model remains somewhat controversial. Quantum tunneling for protons has been observed in tryptamine. This suggests that enzyme catalysis may be more accurately characterized as "through the barrier" rather than the traditional model, which requires substrates to go "over" a lowered energy barrier.
# Inhibition
File:Competitive inhibition.svg
File:Inhibition.png
Enzyme reaction rates can be decreased by various types of enzyme inhibitors.
In competitive inhibition, the inhibitor and substrate compete for the enzyme (i.e., they can not bind at the same time). Often competitive inhibitors strongly resemble the real substrate of the enzyme. For example, methotrexate is a competitive inhibitor of the enzyme dihydrofolate reductase, which catalyzes the reduction of dihydrofolate to tetrahydrofolate. The similarity between the structures of folic acid and this drug are shown in the figure to the right bottom. Note that binding of the inhibitor need not be to the substrate binding site (as frequently stated), if binding of the inhibitor changes the conformation of the enzyme to prevent substrate binding and vice versa. In competitive inhibition the maximal velocity of the reaction is not changed, but higher substrate concentrations are required to reach a given velocity, increasing the apparent Km.
In uncompetitive inhibition the inhibitor can not bind to the free enzyme, but only to the ES-complex. The EIS-complex thus formed is enzymatically inactive. This type of inhibition is rare, but may occur in multimeric enzymes.
Non-competitive inhibitors can bind to the enzyme at the same time as the substrate, i.e. they never bind to the active site. Both the EI and EIS complexes are enzymatically inactive. Because the inhibitor can not be driven from the enzyme by higher substrate concentration (in contrast to competitive inhibition), the apparent Vmax changes. But because the substrate can still bind to the enzyme, the Km stays the same.
This type of inhibition resembles the non-competitive, except that the EIS-complex has residual enzymatic activity.
In many organisms inhibitors may act as part of a feedback mechanism. If an enzyme produces too much of one substance in the organism, that substance may act as an inhibitor for the enzyme at the beginning of the pathway that produces it, causing production of the substance to slow down or stop when there is sufficient amount. This is a form of negative feedback. Enzymes which are subject to this form of regulation are often multimeric and have allosteric binding sites for regulatory substances. Their substrate/velocity plots are not hyperbolar, but sigmoidal (S-shaped).
Irreversible inhibitors react with the enzyme and form a covalent adduct with the protein. The inactivation is irreversible. These compounds include eflornithine a drug used to treat the parasitic disease sleeping sickness. Penicillin and Aspirin also act in this manner. With these drugs, the compound is bound in the active site and the enzyme then converts the inhibitor into an activated form that reacts irreversibly with one or more amino acid residues.
## Uses of inactivators
Inhibitors are often used as drugs, but they can also act as poisons. However, the difference between a drug and a poison is usually only a matter of amount, since most drugs are toxic at some level, as Paracelsus wrote, "In all things there is a poison, and there is nothing without a poison." Equally, antibiotics and other anti-infective drugs are just specific poisons that kill a pathogen but not its host.
An example of an inactivator being used as a drug is aspirin, which inhibits the COX-1 and COX-2 enzymes that produce the inflammation messenger prostaglandin, thus suppressing pain and inflammation. The poison cyanide is an irreversible enzyme inactivator that combines with the copper and iron in the active site of the enzyme cytochrome c oxidase and blocks cellular respiration.
# Biological function
Enzymes serve a wide variety of functions inside living organisms. They are indispensable for signal transduction and cell regulation, often via kinases and phosphatases. They also generate movement, with myosin hydrolysing ATP to generate muscle contraction and also moving cargo around the cell as part of the cytoskeleton. Other ATPases in the cell membrane are ion pumps involved in active transport. Enzymes are also involved in more exotic functions, such as luciferase generating light in fireflies. Viruses can also contain enzymes for infecting cells, such as the HIV integrase and reverse transcriptase, or for viral release from cells, like the influenza virus neuraminidase.
An important function of enzymes is in the digestive systems of animals. Enzymes such as amylases and proteases break down large molecules (starch or proteins, respectively) into smaller ones, so they can be absorbed by the intestines. Starch molecules, for example, are too large to be absorbed from the intestine, but enzymes hydrolyse the starch chains into smaller molecules such as maltose and eventually glucose, which can then be absorbed. Different enzymes digest different food substances. In ruminants which have a herbivorous diets, microorganisms in the gut produce another enzyme, cellulase to break down the cellulose cell walls of plant fiber.
Several enzymes can work together in a specific order, creating metabolic pathways. In a metabolic pathway, one enzyme takes the product of another enzyme as a substrate. After the catalytic reaction, the product is then passed on to another enzyme. Sometimes more than one enzyme can catalyze the same reaction in parallel, this can allow more complex regulation: with for example a low constant activity being provided by one enzyme but an inducible high activity from a second enzyme.
Enzymes determine what steps occur in these pathways. Without enzymes, metabolism would neither progress through the same steps, nor be fast enough to serve the needs of the cell. Indeed, a metabolic pathway such as glycolysis could not exist independently of enzymes. Glucose, for example, can react directly with ATP to become phosphorylated at one or more of its carbons. In the absence of enzymes, this occurs so slowly as to be insignificant. However, if hexokinase is added, these slow reactions continue to take place except that phosphorylation at carbon 6 occurs so rapidly that if the mixture is tested a short time later, glucose-6-phosphate is found to be the only significant product. Consequently, the network of metabolic pathways within each cell depends on the set of functional enzymes that are present.
# Control of activity
There are five main ways that enzyme activity is controlled in the cell.
- Enzyme production (transcription and translation of enzyme genes) can be enhanced or diminished by a cell in response to changes in the cell's environment. This form of gene regulation is called enzyme induction and inhibition. For example, bacteria may become resistant to antibiotics such as penicillin because enzymes called beta-lactamases are induced that hydrolyse the crucial beta-lactam ring within the penicillin molecule. Another example are enzymes in the liver called cytochrome P450 oxidases, which are important in drug metabolism. Induction or inhibition of these enzymes can cause drug interactions.
- Enzymes can be compartmentalized, with different metabolic pathways occurring in different cellular compartments. For example, fatty acids are synthesized by one set of enzymes in the cytosol, endoplasmic reticulum and the Golgi apparatus and used by a different set of enzymes as a source of energy in the mitochondrion, through β-oxidation.
- Enzymes can be regulated by inhibitors and activators. For example, the end product(s) of a metabolic pathway are often inhibitors for one of the first enzymes of the pathway (usually the first irreversible step, called committed step), thus regulating the amount of end product made by the pathways. Such a regulatory mechanism is called a negative feedback mechanism, because the amount of the end product produced is regulated by its own concentration. Negative feedback mechanism can effectively adjust the rate of synthesis of intermediate metabolites according to the demands of the cells. This helps allocate materials and energy economically, and prevents the manufacture of excess end products. Like other homeostatic devices, the control of enzymatic action helps to maintain a stable internal environment in living organisms.
- Enzymes can be regulated through post-translational modification. This can include phosphorylation, myristoylation and glycosylation. For example, in the response to insulin, the phosphorylation of multiple enzymes, including glycogen synthase, helps control the synthesis or degradation of glycogen and allows the cell to respond to changes in blood sugar. Another example of post-translational modification is the cleavage of the polypeptide chain. Chymotrypsin, a digestive protease, is produced in inactive form as chymotrypsinogen in the pancreas and transported in this form to the stomach where it is activated. This stops the enzyme from digesting the pancreas or other tissues before it enters the gut. This type of inactive precursor to an enzyme is known as a zymogen.
- Some enzymes may become activated when localized to a different environment (eg. from a reducing (cytoplasm) to an oxidising (periplasm) environment, high pH to low pH etc). For example, hemagglutinin in the influenza virus is activated by a conformational change caused by the acidic conditions, these occur when it is taken up inside its host cell and enters the lysosome.
# Involvement in disease
Since the tight control of enzyme activity is essential for homeostasis, any malfunction (mutation, overproduction, underproduction or deletion) of a single critical enzyme can lead to a genetic disease. The importance of enzymes is shown by the fact that a lethal illness can be caused by the malfunction of just one type of enzyme out of the thousands of types present in our bodies.
One example is the most common type of phenylketonuria. A mutation of a single amino acid in the enzyme phenylalanine hydroxylase, which catalyzes the first step in the degradation of phenylalanine, results in build-up of phenylalanine and related products. This can lead to mental retardation if the disease is untreated.
Another example is when germline mutations in genes coding for DNA repair enzymes cause hereditary cancer syndromes such as xeroderma pigmentosum. Defects in these enzymes cause cancer since the body is less able to repair mutations in the genome. This causes a slow accumulation of mutations and results in the development of many types of cancer in the sufferer.
# Naming conventions
An enzyme's name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase. Examples are lactase, alcohol dehydrogenase and DNA polymerase. This may result in different enzymes, called isoenzymes, with the same function having the same basic name. Isoenzymes have a different amino acid sequence and might be distinguished by their optimal pH, kinetic properties or immunologically. Furthermore, the normal physiological reaction an enzyme catalyzes may not be the same as under artificial conditions. This can result in the same enzyme being identified with two different names. E.g. Glucose isomerase, used industrially to convert glucose into the sweetener fructose, is a xylose isomerase in vivo.
The International Union of Biochemistry and Molecular Biology have developed a nomenclature for enzymes, the EC numbers; each enzyme is described by a sequence of four numbers preceded by "EC".
The first number broadly classifies the enzyme based on its mechanism:
The top-level classification is
- EC 1 Oxidoreductases: catalyze oxidation/reduction reactions
- EC 2 Transferases: transfer a functional group (e.g. a methyl or phosphate group)
- EC 3 Hydrolases: catalyze the hydrolysis of various bonds
- EC 4 Lyases: cleave various bonds by means other than hydrolysis and oxidation
- EC 5 Isomerases: catalyze isomerization changes within a single molecule
- EC 6 Ligases: join two molecules with covalent bonds
The complete nomenclature can be browsed at /.
# Industrial applications
Enzymes are used in the chemical industry and other industrial applications when extremely specific catalysts are required. However, enzymes in general are limited in the number of reactions they have evolved to catalyze and also by their lack of stability in organic solvents and at high temperatures. Consequently, protein engineering is an active area of research and involves attempts to create new enzymes with novel properties, either through rational design or in vitro evolution. | Enzyme
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Enzymes are biomolecules that catalyze (i.e. increase the rates of) chemical reactions.[1][2] Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, the products. Almost all processes in a biological cell need enzymes in order to occur at significant rates. Since enzymes are extremely selective for their substrates and speed up only a few reactions from among many possibilities, the set of enzymes made in a cell determines which metabolic pathways occur in that cell.
Like all catalysts, enzymes work by lowering the activation energy (Ea or ΔG‡) for a reaction, thus dramatically increasing the rate of the reaction. Most enzyme reaction rates are millions of times faster than those of comparable uncatalyzed reactions. As with all catalysts, enzymes are not consumed by the reactions they catalyze, nor do they alter the equilibrium of these reactions. However, enzymes do differ from most other catalysts by being much more specific. Enzymes are known to catalyze about 4,000 biochemical reactions.[3] A few RNA molecules called ribozymes catalyze reactions, with an important example being some parts of the ribosome.[4][5] Synthetic molecules called artificial enzymes also display enzyme-like catalysis.[6]
Enzyme activity can be affected by other molecules. Inhibitors are molecules that decrease enzyme activity; activators are molecules that increase activity. Many drugs and poisons are enzyme inhibitors. Activity is also affected by temperature, chemical environment (e.g. pH), and the concentration of substrate. Some enzymes are used commercially, for example, in the synthesis of antibiotics. In addition, some household products use enzymes to speed up biochemical reactions (e.g., enzymes in biological washing powders break down protein or fat stains on clothes; enzymes in meat tenderizers break down proteins, making the meat easier to chew).
# Etymology and history
As early as the late 1700s and early 1800s, the digestion of meat by stomach secretions[7] and the conversion of starch to sugars by plant extracts and saliva were known. However, the mechanism by which this occurred had not been identified.[8]
In the 19th century, when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur came to the conclusion that this fermentation was catalyzed by a vital force contained within the yeast cells called "ferments", which were thought to function only within living organisms. He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells."[9]
In 1878 German physiologist Wilhelm Kühne (1837–1900) first used the term enzyme, which comes from Greek ενζυμον "in leaven", to describe this process. The word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment used to refer to chemical activity produced by living organisms.
In 1897 Eduard Buchner began to study the ability of yeast extracts that lacked any living yeast cells to ferment sugar. In a series of experiments at the University of Berlin, he found that the sugar was fermented even when there were no living yeast cells in the mixture.[10] He named the enzyme that brought about the fermentation of sucrose "zymase".[11] In 1907 he received the Nobel Prize in Chemistry "for his biochemical research and his discovery of cell-free fermentation". Following Buchner's example; enzymes are usually named according to the reaction they carry out. Typically the suffix -ase is added to the name of the substrate (e.g., lactase is the enzyme that cleaves lactose) or the type of reaction (e.g., DNA polymerase forms DNA polymers).
Having shown that enzymes could function outside a living cell, the next step was to determine their biochemical nature. Many early workers noted that enzymatic activity was associated with proteins, but several scientists (such as Nobel laureate Richard Willstätter) argued that proteins were merely carriers for the true enzymes and that proteins per se were incapable of catalysis. However, in 1926, James B. Sumner showed that the enzyme urease was a pure protein and crystallized it; Sumner did likewise for the enzyme catalase in 1937. The conclusion that pure proteins can be enzymes was definitively proved by Northrop and Stanley, who worked on the digestive enzymes pepsin (1930), trypsin and chymotrypsin. These three scientists were awarded the 1946 Nobel Prize in Chemistry.[12]
This discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This was first done for lysozyme, an enzyme found in tears, saliva and egg whites that digests the coating of some bacteria; the structure was solved by a group led by David Chilton Phillips and published in 1965.[13] This high-resolution structure of lysozyme marked the beginning of the field of structural biology and the effort to understand how enzymes work at an atomic level of detail.
# Structures and mechanisms
Enzymes are generally globular proteins and range from just 62 amino acid residues in size, for the monomer of 4-oxalocrotonate tautomerase,[14] to over 2,500 residues in the animal fatty acid synthase.[15] A small number of RNA-based biological catalysts exist, with the most common being the ribosome, these are either referred to as RNA-enzymes, or ribozymes. The activities of enzymes are determined by their three-dimensional structure.[16] Most enzymes are much larger than the substrates they act on, and only a small portion of the enzyme (around 3–4 amino acids) is directly involved in catalysis.[17] The region that contains these catalytic residues, binds the substrate, and then carries out the reaction is known as the active site. Enzymes can also contain sites that bind cofactors, which are needed for catalysis. Some enzymes also have binding sites for small molecules, which are often direct or indirect products or substrates of the reaction catalyzed. This binding can serve to increase or decrease the enzyme's activity, providing a means for feedback regulation.
Like all proteins, enzymes are made as long, linear chains of amino acids that fold to produce a three-dimensional product. Each unique amino acid sequence produces a specific structure, which has unique properties. Individual protein chains may sometimes group together to form a protein complex. Most enzymes can be denatured—that is, unfolded and inactivated—by heating or chemical denaturants, which disrupt the three-dimensional structure of the protein. Depending on the enzyme, denaturation may be reversible or irreversible.
## Specificity
Enzymes are usually very specific as to which reactions they catalyze and the substrates that are involved in these reactions. Complementary shape, charge and hydrophilic/hydrophobic characteristics of enzymes and substrates are responsible for this specificity. Enzymes can also show impressive levels of stereospecificity, regioselectivity and chemoselectivity.[18]
Some of the enzymes showing the highest specificity and accuracy are involved in the copying and expression of the genome. These enzymes have "proof-reading" mechanisms. Here, an enzyme such as DNA polymerase catalyzes a reaction in a first step and then checks that the product is correct in a second step.[19] This two-step process results in average error rates of less than 1 error in 100 million reactions in high-fidelity mammalian polymerases.[20] Similar proofreading mechanisms are also found in RNA polymerase,[21] aminoacyl tRNA synthetases[22] and ribosomes.[23]
Some enzymes that produce secondary metabolites are described as promiscuous, as they can act on a relatively broad range of different substrates. It has been suggested that this broad substrate specificity is important for the evolution of new biosynthetic pathways.[24]
### "Lock and key" model
Enzymes are very specific, and it was suggested by Emil Fischer in 1894 that this was because both the enzyme and the substrate possess specific complementary geometric shapes that fit exactly into one another.[25] This is often referred to as "the lock and key" model. However, while this model explains enzyme specificity, it fails to explain the stabilization of the transition state that enzymes achieve.
The "lock and key" model has proven inaccurate and the induced fit model is the most currently accepted enzyme-substrate-coenzyme figure.
### Induced fit model
In 1958 Daniel Koshland suggested a modification to the lock and key model: since enzymes are rather flexible structures, the active site is continually reshaped by interactions with the substrate as the substrate interacts with the enzyme.[26] As a result, the substrate does not simply bind to a rigid active site, the amino acid side chains which make up the active site are moulded into the precise positions that enable the enzyme to perform its catalytic function. In some cases, such as glycosidases, the substrate molecule also changes shape slightly as it enters the active site.[27] The active site continues to change until the substrate is completely bound, at which point the final shape and charge is determined.[28]
## Mechanisms
Enzymes can act in several ways, all of which lower ΔG‡:[29]
- Lowering the activation energy by creating an environment in which the transition state is stabilized (e.g. straining the shape of a substrate - by binding the transition-state conformation of the substrate/product molecules, the enzyme distorts the bound substrate(s) into their transition state form, thereby reducing the amount of energy required to complete the transition).
- Lowering the energy of the transition state, but without distorting the substrate, by creating an environment with the opposite charge distribution to that of the transition state.
- Providing an alternative pathway. For example, temporarily reacting with the substrate to form an intermediate ES complex, which would be impossible in the absence of the enzyme.
- Reducing the reaction entropy change by bringing substrates together in the correct orientation to react. Considering ΔH‡ alone overlooks this effect.
Interestingly, this entropic effect involves destabilization of the ground state,[30] and its contribution to catalysis is relatively small.[31]
### Transition State Stabilization
The understanding of the origin of the reduction of ΔG‡ requires one to find out how the enzymes can stabilize its transition state more than the transition state of the uncatalyzed reaction. Apparently, the most effective way for reaching large stabilization is the use of electrostatic effects, in particular, by having a relatively fixed polar environment that is oriented toward the charge distribution of the transition state.[32] Such an environment does not exist in the uncatalyzed reaction in water.
### Dynamics and function
Recent investigations have provided new insights into the connection between internal dynamics of enzymes and their mechanism of catalysis.[33][34][35]
An enzyme's internal dynamics are the movement of its internal parts (e.g. amino acids, a group of amino acids, a loop region, an alpha helix, neighboring beta-sheets or even an entire domain) of these proteins. These movements occur at various time-scales ranging from femtoseconds to seconds. Networks of protein residues throughout an enzyme's structure can contribute to catalysis through dynamic motions.[36][37][38][39] Protein motions are vital to many enzymes, but whether small and fast vibrations, or larger and slower conformational movements are more important depends on the type of reaction involved. However, although these movements are important in binding and releasing substrates and products, it is not clear if protein movements help to accelerate the chemical steps in enzymatic reactions.[40] These new insights also have implications in understanding allosteric effects and developing new drugs.
## Allosteric modulation
Allosteric enzymes change their structure in response to binding of effectors. Modulation can be direct, where the effector binds directly to binding sites in the enzyme, or indirect, where the effector binds to other proteins or protein subunits that interact with the allosteric enzyme and thus influence catalytic activity.
# Cofactors and coenzymes
## Cofactors
Some enzymes do not need any additional components to show full activity. However, others require non-protein molecules called cofactors to be bound for activity.[41] Cofactors can be either inorganic (e.g., metal ions and iron-sulfur clusters) or organic compounds, (e.g., flavin and heme). Organic cofactors can be either prosthetic groups, which are tightly bound to an enzyme, or coenzymes, which are released from the enzyme's active site during the reaction. Coenzymes include NADH, NADPH and adenosine triphosphate. These molecules act to transfer chemical groups between enzymes.[42]
An example of an enzyme that contains a cofactor is carbonic anhydrase, and is shown in the ribbon diagram above with a zinc cofactor bound as part of its active site.[43] These tightly-bound molecules are usually found in the active site and are involved in catalysis. For example, flavin and heme cofactors are often involved in redox reactions.
Enzymes that require a cofactor but do not have one bound are called apoenzymes or apoproteins. An apoenzyme together with its cofactor(s) is called a holoenzyme (this is the active form). Most cofactors are not covalently attached to an enzyme, but are very tightly bound. However, organic prosthetic groups can be covalently bound (e.g., thiamine pyrophosphate in the enzyme pyruvate dehydrogenase).
## Coenzymes
Coenzymes are small organic molecules that transport chemical groups from one enzyme to another.[44] Some of these chemicals such as riboflavin, thiamine and folic acid are vitamins, this is when these compounds cannot be made in the body and must be acquired from the diet. The chemical groups carried include the hydride ion (H-) carried by NAD or NADP+, the acetyl group carried by coenzyme A, formyl, methenyl or methyl groups carried by folic acid and the methyl group carried by S-adenosylmethionine.
Since coenzymes are chemically changed as a consequence of enzyme action, it is useful to consider coenzymes to be a special class of substrates, or second substrates, which are common to many different enzymes. For example, about 700 enzymes are known to use the coenzyme NADH.[45]
Coenzymes are usually regenerated and their concentrations maintained at a steady level inside the cell: for example, NADPH is regenerated through the pentose phosphate pathway and S-adenosylmethionine by methionine adenosyltransferase.
# Thermodynamics
As all catalysts, enzymes do not alter the position of the chemical equilibrium of the reaction. Usually, in the presence of an enzyme, the reaction runs in the same direction as it would without the enzyme, just more quickly. However, in the absence of the enzyme, other possible uncatalyzed, "spontaneous" reactions might lead to different products, because in those conditions this different product is formed faster.
Furthermore, enzymes can couple two or more reactions, so that a thermodynamically favorable reaction can be used to "drive" a thermodynamically unfavorable one. For example, the hydrolysis of ATP is often used to drive other chemical reactions.
Enzymes catalyze the forward and backward reactions equally. They do not alter the equilibrium itself, but only the speed at which it is reached. For example, carbonic anhydrase catalyzes its reaction in either direction depending on the concentration of its reactants.
H_2CO_3}</math> (in tissues; high CO2 concentration)
CO_2 + H_2O}</math> (in lungs; low CO2 concentration)
Nevertheless, if the equilibrium is greatly displaced in one direction, that is, in a very exergonic reaction, the reaction is effectively irreversible. Under these conditions the enzyme will, in fact, only catalyze the reaction in the thermodynamically allowed direction.
# Kinetics
Enzyme kinetics is the investigation of how enzymes bind substrates and turn them into products. The rate data used in kinetic analyses are obtained from enzyme assays.
In 1902 Victor Henri[46] proposed a quantitative theory of enzyme kinetics, but his experimental data were not useful because the significance of the hydrogen ion concentration was not yet appreciated. After Peter Lauritz Sørensen had defined the logarithmic pH-scale and introduced the concept of buffering in 1909[47] the German chemist Leonor Michaelis and his Canadian postdoc Maud Leonora Menten repeated Henri's experiments and confirmed his equation which is referred to as Henri-Michaelis-Menten kinetics (sometimes also Michaelis-Menten kinetics).[48] Their work was further developed by G. E. Briggs and J. B. S. Haldane, who derived kinetic equations that are still widely used today.[49]
The major contribution of Henri was to think of enzyme reactions in two stages. In the first, the substrate binds reversibly to the enzyme, forming the enzyme-substrate complex. This is sometimes called the Michaelis complex. The enzyme then catalyzes the chemical step in the reaction and releases the product.
File:Michaelis-Menten saturation curve of an enzyme reaction.svg
Enzymes can catalyze up to several million reactions per second. For example, the reaction catalyzed by orotidine 5'-phosphate decarboxylase will consume half of its substrate in 78 million years if no enzyme is present. However, when the decarboxylase is added, the same process takes just 25 milliseconds.[50] Enzyme rates depend on solution conditions and substrate concentration. Conditions that denature the protein abolish enzyme activity, such as high temperatures, extremes of pH or high salt concentrations, while raising substrate concentration tends to increase activity. To find the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation is seen. This is shown in the saturation curve on the right. Saturation happens because, as substrate concentration increases, more and more of the free enzyme is converted into the substrate-bound ES form. At the maximum velocity (Vmax) of the enzyme, all the enzyme active sites are bound to substrate, and the amount of ES complex is the same as the total amount of enzyme.
However, Vmax is only one kinetic constant of enzymes. The amount of substrate needed to achieve a given rate of reaction is also important. This is given by the Michaelis-Menten constant (Km), which is the substrate concentration required for an enzyme to reach one-half its maximum velocity. Each enzyme has a characteristic Km for a given substrate, and this can show how tight the binding of the substrate is to the enzyme. Another useful constant is kcat, which is the number of substrate molecules handled by one active site per second.
The efficiency of an enzyme can be expressed in terms of kcat/Km. This is also called the specificity constant and incorporates the rate constants for all steps in the reaction. Because the specificity constant reflects both affinity and catalytic ability, it is useful for comparing different enzymes against each other, or the same enzyme with different substrates. The theoretical maximum for the specificity constant is called the diffusion limit and is about 108 to 109 (M-1 s-1). At this point every collision of the enzyme with its substrate will result in catalysis, and the rate of product formation is not limited by the reaction rate but by the diffusion rate. Enzymes with this property are called catalytically perfect or kinetically perfect. Example of such enzymes are triose-phosphate isomerase, carbonic anhydrase, acetylcholinesterase, catalase, fumarase, β-lactamase, and superoxide dismutase.
Michaelis-Menten kinetics relies on the law of mass action, which is derived from the assumptions of free diffusion and thermodynamically-driven random collision. However, many biochemical or cellular processes deviate significantly from these conditions, because of very high concentrations, phase-separation of the enzyme/substrate/product, or one or two-dimensional molecular movement.[51] In these situations, a fractal Michaelis-Menten kinetics may be applied.[52][53][54][55]
Some enzymes operate with kinetics which are faster than diffusion rates, which would seem to be impossible. Several mechanisms have been invoked to explain this phenomenon. Some proteins are believed to accelerate catalysis by drawing their substrate in and pre-orienting them by using dipolar electric fields. Other models invoke a quantum-mechanical tunneling explanation, whereby a proton or an electron can tunnel through activation barriers, although for proton tunneling this model remains somewhat controversial.[56][57] Quantum tunneling for protons has been observed in tryptamine.[58] This suggests that enzyme catalysis may be more accurately characterized as "through the barrier" rather than the traditional model, which requires substrates to go "over" a lowered energy barrier.
# Inhibition
File:Competitive inhibition.svg
File:Inhibition.png
Enzyme reaction rates can be decreased by various types of enzyme inhibitors.
In competitive inhibition, the inhibitor and substrate compete for the enzyme (i.e., they can not bind at the same time). Often competitive inhibitors strongly resemble the real substrate of the enzyme. For example, methotrexate is a competitive inhibitor of the enzyme dihydrofolate reductase, which catalyzes the reduction of dihydrofolate to tetrahydrofolate. The similarity between the structures of folic acid and this drug are shown in the figure to the right bottom. Note that binding of the inhibitor need not be to the substrate binding site (as frequently stated), if binding of the inhibitor changes the conformation of the enzyme to prevent substrate binding and vice versa. In competitive inhibition the maximal velocity of the reaction is not changed, but higher substrate concentrations are required to reach a given velocity, increasing the apparent Km.
In uncompetitive inhibition the inhibitor can not bind to the free enzyme, but only to the ES-complex. The EIS-complex thus formed is enzymatically inactive. This type of inhibition is rare, but may occur in multimeric enzymes.
Non-competitive inhibitors can bind to the enzyme at the same time as the substrate, i.e. they never bind to the active site. Both the EI and EIS complexes are enzymatically inactive. Because the inhibitor can not be driven from the enzyme by higher substrate concentration (in contrast to competitive inhibition), the apparent Vmax changes. But because the substrate can still bind to the enzyme, the Km stays the same.
This type of inhibition resembles the non-competitive, except that the EIS-complex has residual enzymatic activity.
In many organisms inhibitors may act as part of a feedback mechanism. If an enzyme produces too much of one substance in the organism, that substance may act as an inhibitor for the enzyme at the beginning of the pathway that produces it, causing production of the substance to slow down or stop when there is sufficient amount. This is a form of negative feedback. Enzymes which are subject to this form of regulation are often multimeric and have allosteric binding sites for regulatory substances. Their substrate/velocity plots are not hyperbolar, but sigmoidal (S-shaped).
Irreversible inhibitors react with the enzyme and form a covalent adduct with the protein. The inactivation is irreversible. These compounds include eflornithine a drug used to treat the parasitic disease sleeping sickness.[60] Penicillin and Aspirin also act in this manner. With these drugs, the compound is bound in the active site and the enzyme then converts the inhibitor into an activated form that reacts irreversibly with one or more amino acid residues.
## Uses of inactivators
Inhibitors are often used as drugs, but they can also act as poisons. However, the difference between a drug and a poison is usually only a matter of amount, since most drugs are toxic at some level, as Paracelsus wrote, "In all things there is a poison, and there is nothing without a poison."[61] Equally, antibiotics and other anti-infective drugs are just specific poisons that kill a pathogen but not its host.
An example of an inactivator being used as a drug is aspirin, which inhibits the COX-1 and COX-2 enzymes that produce the inflammation messenger prostaglandin, thus suppressing pain and inflammation. The poison cyanide is an irreversible enzyme inactivator that combines with the copper and iron in the active site of the enzyme cytochrome c oxidase and blocks cellular respiration.[62]
# Biological function
Enzymes serve a wide variety of functions inside living organisms. They are indispensable for signal transduction and cell regulation, often via kinases and phosphatases.[63] They also generate movement, with myosin hydrolysing ATP to generate muscle contraction and also moving cargo around the cell as part of the cytoskeleton.[64] Other ATPases in the cell membrane are ion pumps involved in active transport. Enzymes are also involved in more exotic functions, such as luciferase generating light in fireflies.[65] Viruses can also contain enzymes for infecting cells, such as the HIV integrase and reverse transcriptase, or for viral release from cells, like the influenza virus neuraminidase.
An important function of enzymes is in the digestive systems of animals. Enzymes such as amylases and proteases break down large molecules (starch or proteins, respectively) into smaller ones, so they can be absorbed by the intestines. Starch molecules, for example, are too large to be absorbed from the intestine, but enzymes hydrolyse the starch chains into smaller molecules such as maltose and eventually glucose, which can then be absorbed. Different enzymes digest different food substances. In ruminants which have a herbivorous diets, microorganisms in the gut produce another enzyme, cellulase to break down the cellulose cell walls of plant fiber.[66]
Several enzymes can work together in a specific order, creating metabolic pathways. In a metabolic pathway, one enzyme takes the product of another enzyme as a substrate. After the catalytic reaction, the product is then passed on to another enzyme. Sometimes more than one enzyme can catalyze the same reaction in parallel, this can allow more complex regulation: with for example a low constant activity being provided by one enzyme but an inducible high activity from a second enzyme.
Enzymes determine what steps occur in these pathways. Without enzymes, metabolism would neither progress through the same steps, nor be fast enough to serve the needs of the cell. Indeed, a metabolic pathway such as glycolysis could not exist independently of enzymes. Glucose, for example, can react directly with ATP to become phosphorylated at one or more of its carbons. In the absence of enzymes, this occurs so slowly as to be insignificant. However, if hexokinase is added, these slow reactions continue to take place except that phosphorylation at carbon 6 occurs so rapidly that if the mixture is tested a short time later, glucose-6-phosphate is found to be the only significant product. Consequently, the network of metabolic pathways within each cell depends on the set of functional enzymes that are present.
# Control of activity
There are five main ways that enzyme activity is controlled in the cell.
- Enzyme production (transcription and translation of enzyme genes) can be enhanced or diminished by a cell in response to changes in the cell's environment. This form of gene regulation is called enzyme induction and inhibition. For example, bacteria may become resistant to antibiotics such as penicillin because enzymes called beta-lactamases are induced that hydrolyse the crucial beta-lactam ring within the penicillin molecule. Another example are enzymes in the liver called cytochrome P450 oxidases, which are important in drug metabolism. Induction or inhibition of these enzymes can cause drug interactions.
- Enzymes can be compartmentalized, with different metabolic pathways occurring in different cellular compartments. For example, fatty acids are synthesized by one set of enzymes in the cytosol, endoplasmic reticulum and the Golgi apparatus and used by a different set of enzymes as a source of energy in the mitochondrion, through β-oxidation.[67]
- Enzymes can be regulated by inhibitors and activators. For example, the end product(s) of a metabolic pathway are often inhibitors for one of the first enzymes of the pathway (usually the first irreversible step, called committed step), thus regulating the amount of end product made by the pathways. Such a regulatory mechanism is called a negative feedback mechanism, because the amount of the end product produced is regulated by its own concentration. Negative feedback mechanism can effectively adjust the rate of synthesis of intermediate metabolites according to the demands of the cells. This helps allocate materials and energy economically, and prevents the manufacture of excess end products. Like other homeostatic devices, the control of enzymatic action helps to maintain a stable internal environment in living organisms.
- Enzymes can be regulated through post-translational modification. This can include phosphorylation, myristoylation and glycosylation. For example, in the response to insulin, the phosphorylation of multiple enzymes, including glycogen synthase, helps control the synthesis or degradation of glycogen and allows the cell to respond to changes in blood sugar.[68] Another example of post-translational modification is the cleavage of the polypeptide chain. Chymotrypsin, a digestive protease, is produced in inactive form as chymotrypsinogen in the pancreas and transported in this form to the stomach where it is activated. This stops the enzyme from digesting the pancreas or other tissues before it enters the gut. This type of inactive precursor to an enzyme is known as a zymogen.
- Some enzymes may become activated when localized to a different environment (eg. from a reducing (cytoplasm) to an oxidising (periplasm) environment, high pH to low pH etc). For example, hemagglutinin in the influenza virus is activated by a conformational change caused by the acidic conditions, these occur when it is taken up inside its host cell and enters the lysosome.[69]
# Involvement in disease
Since the tight control of enzyme activity is essential for homeostasis, any malfunction (mutation, overproduction, underproduction or deletion) of a single critical enzyme can lead to a genetic disease. The importance of enzymes is shown by the fact that a lethal illness can be caused by the malfunction of just one type of enzyme out of the thousands of types present in our bodies.
One example is the most common type of phenylketonuria. A mutation of a single amino acid in the enzyme phenylalanine hydroxylase, which catalyzes the first step in the degradation of phenylalanine, results in build-up of phenylalanine and related products. This can lead to mental retardation if the disease is untreated.[70]
Another example is when germline mutations in genes coding for DNA repair enzymes cause hereditary cancer syndromes such as xeroderma pigmentosum. Defects in these enzymes cause cancer since the body is less able to repair mutations in the genome. This causes a slow accumulation of mutations and results in the development of many types of cancer in the sufferer.
# Naming conventions
An enzyme's name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase. Examples are lactase, alcohol dehydrogenase and DNA polymerase. This may result in different enzymes, called isoenzymes, with the same function having the same basic name. Isoenzymes have a different amino acid sequence and might be distinguished by their optimal pH, kinetic properties or immunologically. Furthermore, the normal physiological reaction an enzyme catalyzes may not be the same as under artificial conditions. This can result in the same enzyme being identified with two different names. E.g. Glucose isomerase, used industrially to convert glucose into the sweetener fructose, is a xylose isomerase in vivo.
The International Union of Biochemistry and Molecular Biology have developed a nomenclature for enzymes, the EC numbers; each enzyme is described by a sequence of four numbers preceded by "EC".
The first number broadly classifies the enzyme based on its mechanism:
The top-level classification is
- EC 1 Oxidoreductases: catalyze oxidation/reduction reactions
- EC 2 Transferases: transfer a functional group (e.g. a methyl or phosphate group)
- EC 3 Hydrolases: catalyze the hydrolysis of various bonds
- EC 4 Lyases: cleave various bonds by means other than hydrolysis and oxidation
- EC 5 Isomerases: catalyze isomerization changes within a single molecule
- EC 6 Ligases: join two molecules with covalent bonds
The complete nomenclature can be browsed at http://www.chem.qmul.ac.uk/iubmb/enzyme/.
# Industrial applications
Enzymes are used in the chemical industry and other industrial applications when extremely specific catalysts are required. However, enzymes in general are limited in the number of reactions they have evolved to catalyze and also by their lack of stability in organic solvents and at high temperatures. Consequently, protein engineering is an active area of research and involves attempts to create new enzymes with novel properties, either through rational design or in vitro evolution.[71][72] | https://www.wikidoc.org/index.php/Apoenzyme | |
342317d24a85ea0b4ef2234d8f20070c6a461b63 | wikidoc | Aramid | Aramid
Aramid fibers are a class of heat-resistant and strong synthetic fibers. They are used in aerospace and military applications, for ballistic rated body armor fabric, and as an asbestos substitute. The name is a shortened form of "aromatic polyamide". They are fibers in which the chain molecules are highly oriented along the fiber axis, so the strength of the chemical bond can be exploited.
# History
Aromatic polyamides were first introduced in a commercial application in the early 1960s, with the meta-aramid fiber Nomex, by DuPont. This fiber is a very heat resistant material still used in thermal and electrical insulation and also produced by Teijin under the tradename Teijinconex, and in Europe by Kermel under the tradename Kermel since early 1970s.
Based on earlier research by Monsanto and Bayer, a fiber with much higher tenacity and elastic modulus was developed also in the 1960s-1970s by DuPont and Akzo Nobel, both profiting from their knowledge of rayon, polyester and nylon processing.
Much work was done by Stephanie Kwolek in 1961 while working at DuPont and that company was the first to introduce a para-aramid called Kevlar in 1973. A similar fiber called Twaron with roughly the same chemical structure was introduced by AKZO in 1978. Due to earlier patents on the production process, AKZO and Dupont had a patent war in the 1980s. Twaron is currently owned by the Teijin company (see Production).
Aramids are used in many high-tech applications, such as aerospace and military applications, for "bullet-proof" body armor fabric, and as an asbestos substitute.
The Federal Trade Commission definition for aramid fiber is:
A manufactured fiber in which the fiber-forming substance is a long-chain synthetic polyamide in which at least 85% of the amide linkages, (-CO-NH-) are attached directly to two aromatic rings.
# Production
World capacity of Para-aramid production is estimated at about 41.000 tons/yr in 2002 and increases each year with 5-10%. In 2007 this means a total production capacity of around 55.000 tons/yr.
## Polymer preparation
Aramids are generally prepared by the reaction between an amine group and a carboxylic acid halide group. Simple AB homopolymers may look like:
The most well-known aramids (Nomex, Kevlar and Twaron) are AABB polymers. Nomex or Teijinconex contain predominantly the meta-linkage and are poly-metaphenylene isophtalamides (MPIA).
Kevlar and Twaron are both p-phenylene terephtalamide (PPTA), the simplest form of the AABB para polyaramide. PPTA is a product of p-phenylene diamine (PPD) and terephtaloyl dichloride (TDC or TCl).
Production of PPTA relies on a co-solvent with an ionic component (Calcium Chloride (CaCl2) to occupy the hydrogen bonds of the amide groups, and an organic component N-methyl pyrrolidone (NMP) to dissolve the aromatic polymer. Prior to the invention of this process by Leo Vollbracht, working at the Dutch chemical firm AKZO, no practical means of dissolving the polymer was known. The use of this system led to a patent war between AKZO and DuPont.
## Spinning
After production of the polymer, the Aramid fiber is produced by spinning the solved polymer to a solid fiber from a liquid chemical blend. Polymer solvent for spinning PPTA is generally 100% (water free) Sulphuric acid (H2SO4).
## Appearances
- Fiber
- Chopped fiber
- Powder
- Pulp
# Other types of aramids
Beside meta aramids like Nomex, other variations belong to the aramid fiber range. These are mainly of the copolyamide type, best known under the brand name Technora, as developed by Teijin and introduced in 1976. The manufacturing process of Technora reacts PPD and 3,4'-diaminodipenylether (3,4'-ODA) with terephtaloyl chloride (TCl).
This relatively simple process uses only one amide solvent and therefore spinning can be done directly after the polymer production.
# Aramid fiber characteristics
Aramids share a high degree of orientation with other fibers such as Ultra high molecular weight polyethylene, a characteristic which dominates their properties.
## General:
- good resistance to abrasion
- good resistance to organic solvents
- nonconductive
- no melting point, degradation starts from 500°C
- low flammability
- good fabric integrity at elevated temperatures
- sensitive to acids and salts
- sensitive to ultraviolet radiation
- prone to static build-up unless finished
## Para-aramids:
- para-aramid fibers such as Kevlar and Twaron, provide outstanding strength-to-weight properties
- high Young's modulus
- high tenacity,
- low creep
- low elongation at break (~3.5%)
- difficult to dye - usually solution dyed
# Major industrial uses
- flame-resistant clothing
- heat protective clothing and helmets
- body armor, competing with PE based fiber products such as Dyneema and Spectra.
- composite materials
- asbestos replacement (e.g. braking pads)
- hot air filtration fabrics
- tires, newly as Sulfron (sulphur modified Twaron)
- mechanical rubber goods reinforcement
- ropes and cables
- wicks for fire dancing
- optical fiber cable systems
- sail cloth (not necessarily racing boat sails)
- sporting goods
- drumheads
- wind instrument reeds, such as the Fibracell brand
- speaker woofers
- Boathull material
- Fiber reinforced concrete
- Reinforced Thermoplastic Pipes
- tennis strings (e.g. by Ashaway and Prince tennis companies) | Aramid
Aramid fibers are a class of heat-resistant and strong synthetic fibers. They are used in aerospace and military applications, for ballistic rated body armor fabric, and as an asbestos substitute. The name is a shortened form of "aromatic polyamide". They are fibers in which the chain molecules are highly oriented along the fiber axis, so the strength of the chemical bond can be exploited.
# History
Aromatic polyamides were first introduced in a commercial application in the early 1960s, with the meta-aramid fiber Nomex, by DuPont. This fiber is a very heat resistant material still used in thermal and electrical insulation and also produced by Teijin under the tradename Teijinconex, and in Europe by Kermel under the tradename Kermel since early 1970s.
Based on earlier research by Monsanto and Bayer, a fiber with much higher tenacity and elastic modulus was developed also in the 1960s-1970s by DuPont and Akzo Nobel, both profiting from their knowledge of rayon, polyester and nylon processing.
Much work was done by Stephanie Kwolek in 1961 while working at DuPont and that company was the first to introduce a para-aramid called Kevlar in 1973. A similar fiber called Twaron with roughly the same chemical structure was introduced by AKZO in 1978. Due to earlier patents on the production process, AKZO and Dupont had a patent war in the 1980s. Twaron is currently owned by the Teijin company (see Production).
Aramids are used in many high-tech applications, such as aerospace and military applications, for "bullet-proof" body armor fabric, and as an asbestos substitute.
The Federal Trade Commission definition for aramid fiber is:
A manufactured fiber in which the fiber-forming substance is a long-chain synthetic polyamide in which at least 85% of the amide linkages, (-CO-NH-) are attached directly to two aromatic rings.
# Production
World capacity of Para-aramid production is estimated at about 41.000 tons/yr in 2002 and increases each year with 5-10%[1]. In 2007 this means a total production capacity of around 55.000 tons/yr.
## Polymer preparation
Aramids are generally prepared by the reaction between an amine group and a carboxylic acid halide group. Simple AB homopolymers may look like:
The most well-known aramids (Nomex, Kevlar and Twaron) are AABB polymers. Nomex or Teijinconex contain predominantly the meta-linkage and are poly-metaphenylene isophtalamides (MPIA).
Kevlar and Twaron are both p-phenylene terephtalamide (PPTA), the simplest form of the AABB para polyaramide. PPTA is a product of p-phenylene diamine (PPD) and terephtaloyl dichloride (TDC or TCl).
Production of PPTA relies on a co-solvent with an ionic component (Calcium Chloride (CaCl2) to occupy the hydrogen bonds of the amide groups, and an organic component N-methyl pyrrolidone (NMP) to dissolve the aromatic polymer. Prior to the invention of this process by Leo Vollbracht, working at the Dutch chemical firm AKZO, no practical means of dissolving the polymer was known. The use of this system led to a patent war between AKZO and DuPont.
## Spinning
After production of the polymer, the Aramid fiber is produced by spinning the solved polymer to a solid fiber from a liquid chemical blend. Polymer solvent for spinning PPTA is generally 100% (water free) Sulphuric acid (H2SO4).
## Appearances
- Fiber
- Chopped fiber
- Powder
- Pulp
# Other types of aramids
Beside meta aramids like Nomex, other variations belong to the aramid fiber range. These are mainly of the copolyamide type, best known under the brand name Technora, as developed by Teijin and introduced in 1976. The manufacturing process of Technora reacts PPD and 3,4'-diaminodipenylether (3,4'-ODA) with terephtaloyl chloride (TCl). [2]
This relatively simple process uses only one amide solvent and therefore spinning can be done directly after the polymer production.
# Aramid fiber characteristics
Aramids share a high degree of orientation with other fibers such as Ultra high molecular weight polyethylene, a characteristic which dominates their properties.
## General:
- good resistance to abrasion
- good resistance to organic solvents
- nonconductive
- no melting point, degradation starts from 500°C
- low flammability
- good fabric integrity at elevated temperatures
- sensitive to acids and salts
- sensitive to ultraviolet radiation
- prone to static build-up unless finished[3]
## Para-aramids:
- para-aramid fibers such as Kevlar and Twaron, provide outstanding strength-to-weight properties
- high Young's modulus
- high tenacity,
- low creep
- low elongation at break (~3.5%)
- difficult to dye - usually solution dyed [3]
# Major industrial uses
- flame-resistant clothing
- heat protective clothing and helmets
- body armor[4], competing with PE based fiber products such as Dyneema and Spectra.
- composite materials
- asbestos replacement (e.g. braking pads)
- hot air filtration fabrics
- tires, newly as Sulfron (sulphur modified Twaron)
- mechanical rubber goods reinforcement
- ropes and cables
- wicks for fire dancing
- optical fiber cable systems
- sail cloth (not necessarily racing boat sails)
- sporting goods
- drumheads
- wind instrument reeds, such as the Fibracell brand
- speaker woofers
- Boathull material
- Fiber reinforced concrete
- Reinforced Thermoplastic Pipes
- tennis strings (e.g. by Ashaway and Prince tennis companies) | https://www.wikidoc.org/index.php/Aramid | |
288a7c36533daac0b6adfe312d0e02a53d2290db | wikidoc | Areola | Areola
In anatomy, the term areola, plural areolae, (diminutive of Latin area, "open place") is used to describe any small circular area such as the colored skin surrounding the nipple. While it is most commonly used to describe the pigmented area around the human nipple (areola mammae), it can also be used to describe other small circular areas such as the inflamed region surrounding a pimple.
The Merriam-Webster dictionary notes two pronunciations for the term areola; aREola and areOla, with speaker icon pronunciations.
The reason the color of the areola differs from that of the rest of the breast is that the areola roughly delineates where the ducts of the mammary glands are. Careful inspection of a mature human female nipple will reveal several small openings arranged radially around the tip of the nipple (lactiferous ducts) from where milk is released during lactation. Other small openings in the areola are sebaceous glands known as Montgomery's glands (or glands of Montgomery) which provide lubrication to protect the area around the nipple and assist with suckling during lactation. These can be quite obvious and raised above the surface of the areola, giving the appearance of "goose-flesh".
Two polymers contribute to the color of the areola in humans - brown eumelanin and pheomelanin, a red pigment. The relative amount of these pigments determines the color of the areola, which can vary greatly, ranging from pale pink to dark brown, but generally tending to be paler among people with lighter skin tones and darker among people with darker skin tones.
An individual's areolae may also change color over time in response to hormonal changes caused by menstruation, certain medications, and ageing. Most notably, the areolae may darken substantially during pregnancy. Some regression to the original color may occur after the baby is born but, again, this varies from individual to individual.
The size and shape of areolae is also highly variable, with those of sexually mature women usually being larger than those of men and prepubescent girls. Human areolae are mostly circular in shape but many women and some men have areolae that are noticeably elliptical.
The areolae of most men is around 25 mm (1 in) in diameter while those of sexually-mature women may range up to 100 mm (4 in) or more in diameter, with average sizes around 30 mm (1 3/8 in). The areola of women who are lactating or who have particularly large breasts may be even larger. | Areola
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
In anatomy, the term areola, plural areolae, (diminutive of Latin area, "open place") is used to describe any small circular area such as the colored skin surrounding the nipple. While it is most commonly used to describe the pigmented area around the human nipple (areola mammae), it can also be used to describe other small circular areas such as the inflamed region surrounding a pimple.
The Merriam-Webster dictionary notes two pronunciations for the term areola; aREola and areOla, with speaker icon pronunciations.
The reason the color of the areola differs from that of the rest of the breast is that the areola roughly delineates where the ducts of the mammary glands are. Careful inspection of a mature human female nipple will reveal several small openings arranged radially around the tip of the nipple (lactiferous ducts) from where milk is released during lactation. Other small openings in the areola are sebaceous glands known as Montgomery's glands (or glands of Montgomery) which provide lubrication to protect the area around the nipple and assist with suckling during lactation. These can be quite obvious and raised above the surface of the areola, giving the appearance of "goose-flesh".
Two polymers contribute to the color of the areola in humans - brown eumelanin and pheomelanin, a red pigment. The relative amount of these pigments determines the color of the areola, which can vary greatly, ranging from pale pink to dark brown, but generally tending to be paler among people with lighter skin tones and darker among people with darker skin tones.
An individual's areolae may also change color over time in response to hormonal changes caused by menstruation, certain medications, and ageing. Most notably, the areolae may darken substantially during pregnancy. Some regression to the original color may occur after the baby is born but, again, this varies from individual to individual.
The size and shape of areolae is also highly variable, with those of sexually mature women usually being larger than those of men and prepubescent girls. Human areolae are mostly circular in shape but many women and some men have areolae that are noticeably elliptical.
The areolae of most men is around 25 mm (1 in) in diameter while those of sexually-mature women may range up to 100 mm (4 in) or more in diameter, with average sizes around 30 mm (1 3/8 in).[1] The areola of women who are lactating or who have particularly large breasts may be even larger. | https://www.wikidoc.org/index.php/Areola | |
3e6fb3406a0bfad7c06769a29652bda7b6b370e2 | wikidoc | Axilla | Axilla
# Overview
The axilla (or armpit, underarm, or oxter) is the area on the human body directly under the joint where the arm connects to the shoulder.
# Boundaries
Anatomically, the boundaries are as follows:
# Underarm hair
Underarm hair usually grows in the underarms of both females and males, beginning in adolescence.
In modern Western culture, it is common for women to remove underarm hair for aesthetic reasons, while men tend to keep it. Throughout the feminist movement, previously in the hippie culture, and in some areas of the punk rock scene, some women choose to keep their underarm hair for a variety of reasons, from subversion to egalitarianism to comfort.
Recently, many men in the U.S. and Europe have begun to remove underarm hair due to popularization by hairless male models and athletes, and thinking it is embarrassing if they show it when wearing a sleeveless shirt.
# Body odor
Body odor develops in the underarms due in part to the waste products of microorganisms that feed on sebum, the fatty secretions produced by apocrine glands.
A wide variety of deodorant and antiperspirant products are sold for the purpose of mitigating this odor.
# Cultural significance
The underarms are among the locations in the human body which are most vulnerable to tickling.
The sexual attraction to the underarms is called axillism.
# Terminology
The term oxter, pronounced 'ock-ster' is most often used in Scotland, northern England, and Ireland. Northern Ireland generally replaces all other names of underarm for oxter.
The term "underarm" only refers to the outer surface of the axilla. However, the terms are sometimes used interchangeably in casual contexts.
Colloquially, armpit refers to an object or place which is smelly, greasy or otherwise undesirable.
# Additional images
- Superficial muscles of the chest and front of the arm.
- Axillary artery and its branches - anterior view of right upper limb and thorax.
- The veins of the right axilla, viewed from in front.
- The right brachial plexus (infraclavicular portion) in the axillary fossa; viewed from below and in front.
- The left side of the thorax. | Axilla
Template:Infobox Anatomy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
The axilla (or armpit, underarm, or oxter) is the area on the human body directly under the joint where the arm connects to the shoulder.
# Boundaries
Anatomically, the boundaries are as follows:
# Underarm hair
Underarm hair usually grows in the underarms of both females and males, beginning in adolescence.
In modern Western culture, it is common for women to remove underarm hair for aesthetic reasons, while men tend to keep it. Throughout the feminist movement, previously in the hippie culture, and in some areas of the punk rock scene, some women choose to keep their underarm hair for a variety of reasons, from subversion to egalitarianism to comfort.
Recently, many men in the U.S. and Europe have begun to remove underarm hair due to popularization by hairless male models and athletes, and thinking it is embarrassing if they show it when wearing a sleeveless shirt.
# Body odor
Body odor develops in the underarms due in part to the waste products of microorganisms that feed on sebum, the fatty secretions produced by apocrine glands.
A wide variety of deodorant and antiperspirant products are sold for the purpose of mitigating this odor.
# Cultural significance
The underarms are among the locations in the human body which are most vulnerable to tickling.
The sexual attraction to the underarms is called axillism.
# Terminology
The term oxter, pronounced 'ock-ster' is most often used in Scotland,[4] northern England, and Ireland. Northern Ireland generally replaces all other names of underarm for oxter.
The term "underarm" only refers to the outer surface of the axilla.[5] However, the terms are sometimes used interchangeably in casual contexts.
Colloquially, armpit refers to an object or place which is smelly, greasy or otherwise undesirable.[6]
# Additional images
- Superficial muscles of the chest and front of the arm.
- Axillary artery and its branches - anterior view of right upper limb and thorax.
- The veins of the right axilla, viewed from in front.
- The right brachial plexus (infraclavicular portion) in the axillary fossa; viewed from below and in front.
- The left side of the thorax. | https://www.wikidoc.org/index.php/Arm_pit | |
cf3d7a71121c943a8a501e1edc9919ba3b6c3a8c | wikidoc | Arsine | Arsine
# Overview
Arsine is the chemical compound with the formula AsH3. This flammable, pyrophoric, and highly toxic gas is the simplest compound of arsenic. Aside from its lethality, it finds applications in the semiconductor industry and for the synthesis of organoarsenic compounds.
At its standard state, arsine is a colorless, denser-than-air gas that is soluble in water (200 mL/L) and in many organic solvents as well. Whereas arsine itself is odorless, owing to its oxidation by air it is possible to smell a slight, garlic-like scent when the compound is present at about 0.5 ppm. This compound is generally regarded as stable, since at room temperature it decomposes only slowly. At temperatures of ca. 230 °C decomposition to arsenic and hydrogen is rapid. Several factors, such as humidity, presence of light and certain catalysts (namely aluminium) facilitate the rate of decomposition.
AsH3 is a pyramidal molecule with H–As–H angles of 91.8° and three equivalent As–H bonds, each of 1.519 Å length. The term arsine is commonly used to describe a class of organoarsenic compounds of the formula AsH3−xRx, where R = aryl or alkyl. For example, As(C6H5)3, called triphenylarsine, is referred to as "an arsine."
# Discovery
AsH3 was reported in 1775 by Carl Scheele from the reduction of arsenic(III) oxide with zinc and acid. This reaction is a prelude to the Marsh test, described briefly below.
# Synthesis
AsH3 is generally prepared by the reaction of As3+ sources with H− equivalents.
Alternatively, sources of As3− react with protonic reagents to also produce this gas:
# Reactions
The chemical properties of AsH3 are well developed and can be anticipated based on an average of the behavior of PH3 and SbH3.
## Thermal decomposition
Typical for a heavy hydride (e.g., SbH3, H2Te, SnH4), AsH3 is unstable with respect to its elements. In other words, AsH3 is stable kinetically but not thermodynamically.
This decomposition reaction is the basis of the Marsh Test described below, which detects the metallic As.
## Oxidation
Continuing the analogy to SbH3, AsH3 is readily oxidized by O2 or even air:
Arsine will react violently in presence of strong oxidizing agents, such as potassium permanganate, sodium hypochlorite or nitric acid.
## Precursor to metallic derivatives
AsH3 is used as a precursor to metal complexes of "naked" (or "nearly naked") As. Illustrative is the dimanganese species 2AsH, wherein the Mn2AsH core is planar.
## Gutzeit test
A characteristic test for arsenic involves the reaction of AsH3 with Ag+, called the Gutzeit test for arsenic. Although this test has become obsolete in analytical chemistry, the underlying reactions further illustrate the affinity of AsH3 for "soft" metal cations. In the Gutzeit test, AsH3 is generated by reduction of aqueous arsenic compounds, typically arsenites, with Zn in the presence of H2SO4. The evolved gaseous AsH3 is then exposed to AgNO3 either as powder or as a solution. With "solid" AgNO3, AsH3 reacts to produce yellow Ag4AsNO3, whereas AsH3 reacts with a "solution" of AgNO3 to give black Ag3As.
## Acid-base reactions
The acidic properties of the As–H bond are often exploited. Thus, AsH3 can be deprotonated:
Upon reaction with the aluminium trialkyls, AsH3 gives the trimeric 3, where R = (CH3)3C. This reaction is relevant to the mechanism by which GaAs forms from AsH3 (see below).
AsH3 is generally considered non-basic, but it can be protonated by "super acids" to give isolable salts of the tetrahedral species +.
## Reaction with halogen compounds
Reactions of arsine with the halogens (fluorine and chlorine) or some of their compounds, such as nitrogen trichloride, are extremely dangerous and can result in explosions.
## Catenation
In contrast to the behavior of PH3, AsH3 does not form stable chains, although H2As–AsH2 and even H2As–As(H)–AsH2 have been detected. The diarsine is unstable above −100 °C.
# Microelectronics applications
AsH3 is used in the synthesis of semiconducting materials related to microelectronics and solid-state lasers. Related to P, Arsenic is an n-dopant for silicon and germanium. More importantly, AsH3 is used to make the semiconductor GaAs by CVD at 700–900 °C:
# Chemical warfare applications
Since before WWII AsH3 was proposed as a possible chemical warfare weapon. The gas is colorless, almost odourless, and 2.5 times more dense than air, as required for a blanketing effect sought in chemical warfare. It is also lethal in concentrations far lower than those required to smell its garlic-like scent. In spite of these characteristics, arsine was never officially used as a weapon, because of its high flammability and its lower efficacy when compared to the non-flammable alternative phosgene. On the other hand, several organic compounds based on arsine, such as lewisite (β-chlorovinyldichloroarsine), adamsite (diphenylaminearsine), Clark I (diphenylchlorarsine) and Clark II, (diphenylcyanoarsine) have been effectively developed for use in chemical warfare.
# Forensic science and the Marsh test
AsH3 is also well known in forensic science because it is a chemical intermediate in the detection of arsenic poisoning. The old (but extremely sensitive) Marsh test generates AsH3 in the presence of arsenic. This procedure, developed around 1836 by James Marsh, is based upon treating a As-containing sample of a victim's body (typically the stomach) with As-free zinc and dilute sulfuric acid: if the sample contains arsenic, gaseous arsine will form. The gas is swept into a glass tube and decomposed by means of heating around 250–300 °C. The presence of As is indicated by formation of a deposit in the heated part of the equipment. The formation of a black mirror deposit in the cool part of the equipment indicates the presence of Sb.
The Marsh test was widely used by the end of the 19th century and the start of the 20th; nowadays more sophisticated techniques such as atomic spectroscopy, inductively coupled plasma and x-ray fluorescence analysis are employed in the forensic field. Though neutron activation analysis was used to detect trace levels of arsenic in the mid 20th century it has fallen out of use in modern forensics.
# Toxicology
The toxicity of arsine is distinct from that of other arsenic compounds. The main route of exposure is by inhalation, although poisoning after skin contact has also been described. Arsine binds to the haemoglobin of red blood cells, causing them to be destroyed by the body.
The first signs of exposure, which can take several hours to become apparent, are headaches, vertigo and nausea, followed by the symptoms of haemolytic anaemia (high levels of unconjugated bilirubin), haemoglobinuria and nephropathy. In severe cases, the damage to the kidneys can be long-lasting.
Exposure to arsine concentrations of 250 ppm is rapidly fatal: concentrations of 25–30 ppm are fatal for 30 min exposure, and concentrations of 10 ppm can be fatal at longer exposure times. Symptoms of poisoning appear after exposure to concentrations of 0.5 ppm. There is little information on the chronic toxicity of arsine, although it is reasonable to assume that, in common with other arsenic compounds, a long-term exposure could lead to arsenicosis. | Arsine
Template:Chembox new
# Overview
Arsine is the chemical compound with the formula AsH3. This flammable, pyrophoric, and highly toxic gas is the simplest compound of arsenic. Aside from its lethality, it finds applications in the semiconductor industry and for the synthesis of organoarsenic compounds.[1]
At its standard state, arsine is a colorless, denser-than-air gas that is soluble in water (200 mL/L) and in many organic solvents as well. Whereas arsine itself is odorless, owing to its oxidation by air it is possible to smell a slight, garlic-like scent when the compound is present at about 0.5 ppm. This compound is generally regarded as stable, since at room temperature it decomposes only slowly. At temperatures of ca. 230 °C decomposition to arsenic and hydrogen is rapid. Several factors, such as humidity, presence of light and certain catalysts (namely aluminium) facilitate the rate of decomposition.[1]
AsH3 is a pyramidal molecule with H–As–H angles of 91.8° and three equivalent As–H bonds, each of 1.519 Å length. The term arsine is commonly used to describe a class of organoarsenic compounds of the formula AsH3−xRx, where R = aryl or alkyl. For example, As(C6H5)3, called triphenylarsine, is referred to as "an arsine."
# Discovery
AsH3 was reported in 1775 by Carl Scheele from the reduction of arsenic(III) oxide with zinc and acid. This reaction is a prelude to the Marsh test, described briefly below.
# Synthesis
AsH3 is generally prepared by the reaction of As3+ sources with H− equivalents.[2][3]
Alternatively, sources of As3− react with protonic reagents to also produce this gas:
# Reactions
The chemical properties of AsH3 are well developed and can be anticipated based on an average of the behavior of PH3 and SbH3.
## Thermal decomposition
Typical for a heavy hydride (e.g., SbH3, H2Te, SnH4), AsH3 is unstable with respect to its elements. In other words, AsH3 is stable kinetically but not thermodynamically.
This decomposition reaction is the basis of the Marsh Test described below, which detects the metallic As.
## Oxidation
Continuing the analogy to SbH3, AsH3 is readily oxidized by O2 or even air:
Arsine will react violently in presence of strong oxidizing agents, such as potassium permanganate, sodium hypochlorite or nitric acid.[1]
## Precursor to metallic derivatives
AsH3 is used as a precursor to metal complexes of "naked" (or "nearly naked") As. Illustrative is the dimanganese species [(C5H5)Mn(CO)2]2AsH, wherein the Mn2AsH core is planar.[4]
## Gutzeit test
A characteristic test for arsenic involves the reaction of AsH3 with Ag+, called the Gutzeit test for arsenic.[5] Although this test has become obsolete in analytical chemistry, the underlying reactions further illustrate the affinity of AsH3 for "soft" metal cations. In the Gutzeit test, AsH3 is generated by reduction of aqueous arsenic compounds, typically arsenites, with Zn in the presence of H2SO4. The evolved gaseous AsH3 is then exposed to AgNO3 either as powder or as a solution. With "solid" AgNO3, AsH3 reacts to produce yellow Ag4AsNO3, whereas AsH3 reacts with a "solution" of AgNO3 to give black Ag3As.
## Acid-base reactions
The acidic properties of the As–H bond are often exploited. Thus, AsH3 can be deprotonated:
Upon reaction with the aluminium trialkyls, AsH3 gives the trimeric [R2AlAsH2]3, where R = (CH3)3C.[6] This reaction is relevant to the mechanism by which GaAs forms from AsH3 (see below).
AsH3 is generally considered non-basic, but it can be protonated by "super acids" to give isolable salts of the tetrahedral species [AsH4]+.[7]
## Reaction with halogen compounds
Reactions of arsine with the halogens (fluorine and chlorine) or some of their compounds, such as nitrogen trichloride, are extremely dangerous and can result in explosions.[1]
## Catenation
In contrast to the behavior of PH3, AsH3 does not form stable chains, although H2As–AsH2 and even H2As–As(H)–AsH2 have been detected. The diarsine is unstable above −100 °C.
# Microelectronics applications
AsH3 is used in the synthesis of semiconducting materials related to microelectronics and solid-state lasers. Related to P, Arsenic is an n-dopant for silicon and germanium.[1] More importantly, AsH3 is used to make the semiconductor GaAs by CVD at 700–900 °C:
# Chemical warfare applications
Since before WWII AsH3 was proposed as a possible chemical warfare weapon. The gas is colorless, almost odourless, and 2.5 times more dense than air, as required for a blanketing effect sought in chemical warfare. It is also lethal in concentrations far lower than those required to smell its garlic-like scent. In spite of these characteristics, arsine was never officially used as a weapon, because of its high flammability and its lower efficacy when compared to the non-flammable alternative phosgene. On the other hand, several organic compounds based on arsine, such as lewisite (β-chlorovinyldichloroarsine), adamsite (diphenylaminearsine), Clark I (diphenylchlorarsine) and Clark II, (diphenylcyanoarsine) have been effectively developed for use in chemical warfare.[8]
# Forensic science and the Marsh test
AsH3 is also well known in forensic science because it is a chemical intermediate in the detection of arsenic poisoning. The old (but extremely sensitive) Marsh test generates AsH3 in the presence of arsenic.[3] This procedure, developed around 1836 by James Marsh, is based upon treating a As-containing sample of a victim's body (typically the stomach) with As-free zinc and dilute sulfuric acid: if the sample contains arsenic, gaseous arsine will form. The gas is swept into a glass tube and decomposed by means of heating around 250–300 °C. The presence of As is indicated by formation of a deposit in the heated part of the equipment. The formation of a black mirror deposit in the cool part of the equipment indicates the presence of Sb.
The Marsh test was widely used by the end of the 19th century and the start of the 20th; nowadays more sophisticated techniques such as atomic spectroscopy, inductively coupled plasma and x-ray fluorescence analysis are employed in the forensic field. Though neutron activation analysis was used to detect trace levels of arsenic in the mid 20th century it has fallen out of use in modern forensics.
# Toxicology
The toxicity of arsine is distinct from that of other arsenic compounds. The main route of exposure is by inhalation, although poisoning after skin contact has also been described. Arsine binds to the haemoglobin of red blood cells, causing them to be destroyed by the body.
The first signs of exposure, which can take several hours to become apparent, are headaches, vertigo and nausea, followed by the symptoms of haemolytic anaemia (high levels of unconjugated bilirubin), haemoglobinuria and nephropathy. In severe cases, the damage to the kidneys can be long-lasting.
Exposure to arsine concentrations of 250 ppm is rapidly fatal: concentrations of 25–30 ppm are fatal for 30 min exposure, and concentrations of 10 ppm can be fatal at longer exposure times. Symptoms of poisoning appear after exposure to concentrations of 0.5 ppm. There is little information on the chronic toxicity of arsine, although it is reasonable to assume that, in common with other arsenic compounds, a long-term exposure could lead to arsenicosis. | https://www.wikidoc.org/index.php/Arsine | |
8a410ff3c0d25eb2a7d16befaa3188b7d8c85623 | wikidoc | Artery | Artery
# Overview
Arteries are muscular blood vessels that carry blood away from the heart. All arteries, with the exception of the pulmonary and umbilical arteries, carry oxygenated blood.
The circulatory system is extremely important for sustaining life. Its proper functioning is responsible for the delivery of oxygen and nutrients to all cells, as well as the removal of carbon dioxide and waste products, maintenance of optimum pH, and the mobility of the elements, proteins and cells of the immune system. In developed countries, the two leading causes of death, myocardial infarction and stroke each may directly result from an arterial system that has been slowly and progressively compromised by years of deterioration. (See atherosclerosis).
# Description
The arterial system is the higher-pressure portion of the circulatory system. Arterial pressure varies between the peak pressure during heart contraction, called the systolic pressure, and the minimum, or diastolic pressure between contractions, when the heart rests between cycles. This pressure variation within the artery produces the pulse which is observable in any artery, and reflects heart activity.
# Anatomy
The outermost layer is known as the tunica externa formerly known as "tunica adventitia" and is composed of connective tissue. Inside this layer is the tunica media, or media, which is made up of smooth muscle cells and elastic tissue. The innermost layer, which is in direct contact with the flow of blood is the tunica intima, commonly called the intima. This layer is made up of mainly endothelial cells. The hollow internal cavity in which the blood flows is called the lumen.
# Types of arteries
There are several types of arteries in the body:
## Pulmonary arteries
The pulmonary arteries carry deoxygenated blood that has just returned from the body to the lungs, where carbon dioxide is exchanged for oxygen.
## Systemic arteries
Systemic arteries deliver blood to the arterioles, and then to the capillaries, where nutrients and gasses are exchanged.
## The Aorta
The aorta is the root systemic artery. It receives blood directly from the left ventricle of the heart via the aortic valve. As the aorta branches, and these arteries branch in turn, they become successively smaller in diameter, down to the arteriole. The arterioles supply capillaries which in turn empty into venules.
## Arterioles
Arterioles, the smallest of the true arteries, help regulate blood pressure and deliver blood to the kidneys (capillaries).
## Arterioles and blood pressure
Arterioles have the greatest collective influence on both local blood flow and on overall blood pressure. They are the primary "adjustable nozzles" in the blood system, across which the greatest pressure drop occurs. The combination of heart output (cardiac output) and systemic vascular resistance, which refers to the collective resistance of all of the body's arterioles, are the principal determinants of arterial blood pressure at any given moment.
## Capillaries
The capillaries are where all of the important exchanges happen in the circulatory system. The capillaries are a single cell thick to aid fast and easy diffusion of gases, sugars and other nutrients to surrounding tissues.
### Functions of capillaries
To withstand and adapt to the pressures within, arteries are surrounded by varying thicknesses of smooth muscle which have extensive elastic and inelastic connective tissues.
The pulse pressure, i.e. Systolic vs. Diastolic difference, is determined primarily by the amount of blood ejected by each heart beat, stroke volume, versus the volume and elasticity of the major arteries.
Over time, elevated arterial blood sugar (see Diabetes Mellitus), lipoprotein cholesterol, and pressure, smoking, and other factors are all involved in damaging both the endothelium and walls of the arteries, resulting in atherosclerosis or Diabetes Mellitus.
# History
Among the ancient Greeks, the arteries were considered to be "air holders" that were responsible for the transport of air to the tissues and were connected to the trachea. This theory presumably arose from the fact that the arteries are empty after death: the last beat of the heart pushes the blood through the capillaries and into the veins.
In medieval times, it was recognized that arteries carried a fluid, called "spiritual blood" or "vital spirits", considered to be different from the contents of the veins. This theory went back to Galen. In the late medieval period, the trachea, and ligaments were also called "arteries".
William Harvey described and popularized the modern concept of the circulatory system and the roles of arteries and veins in the 17th century.
Alexis Carrel at the beginning of 20th century first described the technique for vascular suturing and anastomosis and successfully performed many organ transplantations in animals; he thus actually opened the way to modern vascular surgery that was before limited to vessels permanent ligatation. | Artery
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Arteries are muscular blood vessels that carry blood away from the heart.[1] All arteries, with the exception of the pulmonary and umbilical arteries, carry oxygenated blood.
The circulatory system is extremely important for sustaining life. Its proper functioning is responsible for the delivery of oxygen and nutrients to all cells, as well as the removal of carbon dioxide and waste products, maintenance of optimum pH, and the mobility of the elements, proteins and cells of the immune system. In developed countries, the two leading causes of death, myocardial infarction and stroke each may directly result from an arterial system that has been slowly and progressively compromised by years of deterioration. (See atherosclerosis).
# Description
The arterial system is the higher-pressure portion of the circulatory system. Arterial pressure varies between the peak pressure during heart contraction, called the systolic pressure, and the minimum, or diastolic pressure between contractions, when the heart rests between cycles. This pressure variation within the artery produces the pulse which is observable in any artery, and reflects heart activity.
# Anatomy
The outermost layer is known as the tunica externa formerly known as "tunica adventitia" and is composed of connective tissue. Inside this layer is the tunica media, or media, which is made up of smooth muscle cells and elastic tissue. The innermost layer, which is in direct contact with the flow of blood is the tunica intima, commonly called the intima. This layer is made up of mainly endothelial cells. The hollow internal cavity in which the blood flows is called the lumen.
# Types of arteries
There are several types of arteries in the body:
## Pulmonary arteries
The pulmonary arteries carry deoxygenated blood that has just returned from the body to the lungs, where carbon dioxide is exchanged for oxygen.
## Systemic arteries
Systemic arteries deliver blood to the arterioles, and then to the capillaries, where nutrients and gasses are exchanged.
## The Aorta
The aorta is the root systemic artery. It receives blood directly from the left ventricle of the heart via the aortic valve. As the aorta branches, and these arteries branch in turn, they become successively smaller in diameter, down to the arteriole. The arterioles supply capillaries which in turn empty into venules.
## Arterioles
Arterioles, the smallest of the true arteries, help regulate blood pressure and deliver blood to the kidneys (capillaries).
## Arterioles and blood pressure
Arterioles have the greatest collective influence on both local blood flow and on overall blood pressure. They are the primary "adjustable nozzles" in the blood system, across which the greatest pressure drop occurs. The combination of heart output (cardiac output) and systemic vascular resistance, which refers to the collective resistance of all of the body's arterioles, are the principal determinants of arterial blood pressure at any given moment.
## Capillaries
The capillaries are where all of the important exchanges happen in the circulatory system. The capillaries are a single cell thick to aid fast and easy diffusion of gases, sugars and other nutrients to surrounding tissues.
### Functions of capillaries
To withstand and adapt to the pressures within, arteries are surrounded by varying thicknesses of smooth muscle which have extensive elastic and inelastic connective tissues.
The pulse pressure, i.e. Systolic vs. Diastolic difference, is determined primarily by the amount of blood ejected by each heart beat, stroke volume, versus the volume and elasticity of the major arteries.
Over time, elevated arterial blood sugar (see Diabetes Mellitus), lipoprotein cholesterol, and pressure, smoking, and other factors are all involved in damaging both the endothelium and walls of the arteries, resulting in atherosclerosis or Diabetes Mellitus.
# History
Among the ancient Greeks, the arteries were considered to be "air holders" that were responsible for the transport of air to the tissues and were connected to the trachea. This theory presumably arose from the fact that the arteries are empty after death: the last beat of the heart pushes the blood through the capillaries and into the veins.
In medieval times, it was recognized that arteries carried a fluid, called "spiritual blood" or "vital spirits", considered to be different from the contents of the veins. This theory went back to Galen. In the late medieval period, the trachea,[2] and ligaments were also called "arteries".[3]
William Harvey described and popularized the modern concept of the circulatory system and the roles of arteries and veins in the 17th century.
Alexis Carrel at the beginning of 20th century first described the technique for vascular suturing and anastomosis and successfully performed many organ transplantations in animals; he thus actually opened the way to modern vascular surgery that was before limited to vessels permanent ligatation. | https://www.wikidoc.org/index.php/Arterial | |
63efca17dd84e68ac961cd5c9ebbc8cd616d602a | wikidoc | Scurvy | Scurvy
# Overview
Scurvy (N.Lat. scorbutus) is a deficiency disease that results from insufficient intake of vitamin C, which is required for correct collagen synthesis in humans. The scientific name of vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus. Scurvy leads to the formation of liver spots on the skin, spongy gums, and bleeding from all mucous membranes. The spots are most abundant on the thighs and legs, and a person with the ailment looks pale, feels depressed, and is partially immobilized. In advanced scurvy there are open, suppurating wounds and loss of teeth.
Scurvy was at one time common among sailors, pirates and others who were on ships that were out to sea longer than perishable fruits and vegetables could be stored and by soldiers who were similarly separated from these foods for extended periods. It was described by Hippocrates (c. 460 BC–c. 380 BC). Its cause and cure have been known in many native cultures since prehistory. For example, in 1536, the French explorer Jacques Cartier, exploring the St. Lawrence River, used the local natives' knowledge to save his men who were dying of scurvy. He boiled the needles of the arbor vitae tree (Eastern White Cedar) to make a tea that was later shown to contain 50 mg of vitamin C per 100 grams. However it was a Scottish surgeon in the British Royal Navy, James Lind (1716–1794) who first proved it could be treated with citrus fruit in experiments he described in his 1753 book, A Treatise of the Scurvy.
In infants, scurvy is sometimes referred to as Barlow's disease, named after Sir Thomas Barlow (1845–1945), a British physician who described it. (N.B. Barlow's disease may also refer to mitral valve prolapse.) Other eponyms include Moeller's disease and Cheadle's disease.
Scurvy or subclinical scurvy is caused by the lack of vitamin C. In modern western society, scurvy is rarely present in adults, although infants and elderly people are affected. Vitamin C is destroyed by the process of pasteurization, so babies fed with ordinary bottled milk sometimes suffer from scurvy if they are not provided with adequate vitamin supplements. Virtually all commercially available baby formulas contain added vitamin C for this reason; however heat and storage destroy vitamin C. Human breast milk contains sufficient vitamin C, if the mother has an adequate intake to prevent scurvy on her own.
Scurvy is one of the accompanying diseases of malnutrition (other such micronutrient deficiencies are beriberi or pellagra) and thus is still widespread in areas of the world depending on external food aid. Though rare, there are also documented cases of scurvy due to poor dietary choices by people living in industrialized nations.
# Historical Perspective
Scurvy was probably first observed as a disease by Hippocrates. In the 13th century the Crusaders suffered from scurvy frequently, and it has inflicted terrible losses on both besieged and besieger in times of war. Scurvy was one of the limiting factors of marine travel, often killing large numbers of the passengers and crew on long-distance voyages. It even played a significant role in World War I.
The British civilian medical profession of 1614 knew that it was the acidic principle of citrus fruit which was lacking, although they considered any acid as acceptable when ascorbic acid (Vitamin C) was unavailable. In 1614 John Woodall (Surgeon General of the East India Company) published his book "The Surgion's Mate" as a handbook for apprentice surgeons aboard the company's ships. In it he described scurvy as resulting from a dietary deficiency. His recommendation for its cure was fresh food or, if not available, oranges, lemons, limes and tamarinds, or as a last resort, Oil of Vitriol (sulfuric acid).
In 1734, the Leiden-based physician Johann Bachstrom published a book on scurvy in which he stated that "scurvy is solely owing to a total abstinence from fresh vegetable food, and greens; which is alone the primary cause of the disease." and urged the use of fresh fruit and vegetables as a cure. However, it was not until 1747 that James Lind formally proved that scurvy could be treated and prevented by supplementing the diet with citrus fruit such as lemons and lime. Although James Cook succeeded in circumnavigating the world (1768-71) in HM Bark Endeavour without losing a single man to scurvy, his suggested methods, including a diet of sauerkraut and wort of malt, did not reproduce his success, and British sailors throughout the American Revolutionary period continued to suffer from scurvy, particularly in the Channel Fleet. The eradication of scurvy from the Royal Navy was finally due to the chairman of the Navy's Sick and Hurt Board, Gilbert Blane, who finally put Bachstrom and Lind's long-ignored prescription of fresh lemons to use during the Napoleonic Wars. Other navies soon adopted this successful solution.
The plant known as "scurvy grass" acquired its name from the observation that it cured scurvy, but this was of no great help to those who spent months at sea. During sea voyages, it was discovered that sauerkraut was of extremely limited use in preventing scurvy. In the Royal Navy's Arctic expeditions in the 19th century it was widely believed that scurvy was prevented by good hygiene on board ship, regular exercise, and maintaining the morale of the crew, rather than by a diet of fresh food, so that Navy expeditions continued to be plagued by scurvy even while fresh meat was well-known as a practical antiscorbutic among civilian whalers and explorers in the Arctic. At the time Robert Falcon Scott made his two expeditions to the Antarctic in the early 20th century, the prevailing medical theory was that scurvy was caused by "tainted" canned food. It was not until 1932 that the connection between vitamin C and scurvy was established.
The use of limes by the Royal Navy to prevent scurvy gave rise to the name "limey" for a British sailor, which has been since extended to all British in American slang.
# Classification
# Pathophysiology
Normal collagen synthesis depends upon the hydroxylation of proline and lysine residues in the endoplasmic reticulum, to form hydroxyproline and hydroxylysine, respectively. Prolyl and lysyl hydroxylase, the enzymes that catalyze the hydroxylation, require ascorbic acid (vitamin C) to function correctly. With no ascorbic acid, the enzymes cannot hydroxylate proline and lysine, and so normal collagen synthesis cannot be performed.
# Causes
# Differentiating Scurvy from Other Diseases
- Advanced age
- Alcoholism
- Mental illness
- Infant on processed milk without supplementation
- Unusual diet habits
- Osteoporosis
- Idiopathic transient osteoporosis of hip
- Osteomalacia
- Osteogenesis imperfecta
- Multiple myeloma
- Homocystinuria
- Hypermetabolic resorptive osteoporosis.
# Epidemiology and Demographics
# Risk Factors
# Screening
# Natural History, Complications, and Prognosis
## Natural History
## complications
## Prognosis
Untreated scurvy is invariably fatal. However, since all that is required for a full recovery is the resumption of normal vitamin C intake, death from scurvy is rare in modern times.
# Diagnosis
## Diagnostic Criteria
# History and Symptoms
- Dark purplish spots on skin, especially legs.
- spongy gums, often leading to tooth loss.
- bleeding from all mucous membranes.
- Pallor.
- Bleeding gums.
- Sunken eyes
- Opening of healed scars and separation of knitted bone fractures.
## Physical Examination
## Laboratory Findings
## Imaging Findings
## Other Diagnostic Studies
# Treatment
## Medical Therapy
## Surgery
## Prevention
Scurvy can be prevented by a diet that includes certain citrus fruits such as oranges or lemons. Other good sources of vitamin C are fruits such as blackcurrants, guava, kiwi, papaya, tomatoes and strawberries. It can also be found in some vegetables, such as bell peppers, broccoli, potatoes, cabbage, spinach and paprika, as well as some pickled vegetables. Though redundant in the presence of a balanced diet, various nutritional supplements are available that provide ascorbic acid well in excess of that required to prevent scurvy, and even some candies contain vitamin C. | Scurvy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
# Overview
Scurvy (N.Lat. scorbutus) is a deficiency disease that results from insufficient intake of vitamin C, which is required for correct collagen synthesis in humans. The scientific name of vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus. Scurvy leads to the formation of liver spots on the skin, spongy gums, and bleeding from all mucous membranes. The spots are most abundant on the thighs and legs, and a person with the ailment looks pale, feels depressed, and is partially immobilized. In advanced scurvy there are open, suppurating wounds and loss of teeth.
Scurvy was at one time common among sailors, pirates and others who were on ships that were out to sea longer than perishable fruits and vegetables could be stored and by soldiers who were similarly separated from these foods for extended periods. It was described by Hippocrates (c. 460 BC–c. 380 BC). Its cause and cure have been known in many native cultures since prehistory. For example, in 1536, the French explorer Jacques Cartier, exploring the St. Lawrence River, used the local natives' knowledge to save his men who were dying of scurvy. He boiled the needles of the arbor vitae tree (Eastern White Cedar) to make a tea that was later shown to contain 50 mg of vitamin C per 100 grams.[1][2] However it was a Scottish surgeon in the British Royal Navy, James Lind (1716–1794) who first proved it could be treated with citrus fruit in experiments he described in his 1753 book, A Treatise of the Scurvy.
In infants, scurvy is sometimes referred to as Barlow's disease, named after Sir Thomas Barlow (1845–1945),[3] a British physician who described it. (N.B. Barlow's disease may also refer to mitral valve prolapse.) Other eponyms include Moeller's disease and Cheadle's disease.
Scurvy or subclinical scurvy is caused by the lack of vitamin C. In modern western society, scurvy is rarely present in adults, although infants and elderly people are affected.[4] Vitamin C is destroyed by the process of pasteurization, so babies fed with ordinary bottled milk sometimes suffer from scurvy if they are not provided with adequate vitamin supplements. Virtually all commercially available baby formulas contain added vitamin C for this reason; however heat and storage destroy vitamin C. Human breast milk contains sufficient vitamin C, if the mother has an adequate intake to prevent scurvy on her own.
Scurvy is one of the accompanying diseases of malnutrition (other such micronutrient deficiencies are beriberi or pellagra) and thus is still widespread in areas of the world depending on external food aid.[5] Though rare, there are also documented cases of scurvy due to poor dietary choices by people living in industrialized nations.[6]
# Historical Perspective
Scurvy was probably first observed as a disease by Hippocrates.[7] In the 13th century the Crusaders suffered from scurvy frequently, and it has inflicted terrible losses on both besieged and besieger in times of war. Scurvy was one of the limiting factors of marine travel, often killing large numbers of the passengers and crew on long-distance voyages. It even played a significant role in World War I.
The British civilian medical profession of 1614 knew that it was the acidic principle of citrus fruit which was lacking, although they considered any acid as acceptable when ascorbic acid (Vitamin C) was unavailable. In 1614 John Woodall (Surgeon General of the East India Company) published his book "The Surgion's Mate" as a handbook for apprentice surgeons aboard the company's ships. In it he described scurvy as resulting from a dietary deficiency. His recommendation for its cure was fresh food or, if not available, oranges, lemons, limes and tamarinds, or as a last resort, Oil of Vitriol (sulfuric acid).[8]
In 1734, the Leiden-based physician Johann Bachstrom published a book on scurvy in which he stated that "scurvy is solely owing to a total abstinence from fresh vegetable food, and greens; which is alone the primary cause of the disease." and urged the use of fresh fruit and vegetables as a cure. However, it was not until 1747 that James Lind formally proved that scurvy could be treated and prevented by supplementing the diet with citrus fruit such as lemons and lime. Although James Cook succeeded in circumnavigating the world (1768-71) in HM Bark Endeavour without losing a single man to scurvy, his suggested methods, including a diet of sauerkraut and wort of malt, did not reproduce his success, and British sailors throughout the American Revolutionary period continued to suffer from scurvy, particularly in the Channel Fleet. The eradication of scurvy from the Royal Navy was finally due to the chairman of the Navy's Sick and Hurt Board, Gilbert Blane, who finally put Bachstrom and Lind's long-ignored prescription of fresh lemons to use during the Napoleonic Wars. Other navies soon adopted this successful solution.[8]
The plant known as "scurvy grass" acquired its name from the observation that it cured scurvy, but this was of no great help to those who spent months at sea. During sea voyages, it was discovered that sauerkraut was of extremely limited use in preventing scurvy. In the Royal Navy's Arctic expeditions in the 19th century it was widely believed that scurvy was prevented by good hygiene on board ship, regular exercise, and maintaining the morale of the crew, rather than by a diet of fresh food, so that Navy expeditions continued to be plagued by scurvy even while fresh meat was well-known as a practical antiscorbutic among civilian whalers and explorers in the Arctic. At the time Robert Falcon Scott made his two expeditions to the Antarctic in the early 20th century, the prevailing medical theory was that scurvy was caused by "tainted" canned food. It was not until 1932 that the connection between vitamin C and scurvy was established.
The use of limes by the Royal Navy to prevent scurvy gave rise to the name "limey" for a British sailor, which has been since extended to all British in American slang.
# Classification
# Pathophysiology
Normal collagen synthesis depends upon the hydroxylation of proline and lysine residues in the endoplasmic reticulum, to form hydroxyproline and hydroxylysine, respectively. Prolyl and lysyl hydroxylase, the enzymes that catalyze the hydroxylation, require ascorbic acid (vitamin C) to function correctly. With no ascorbic acid, the enzymes cannot hydroxylate proline and lysine, and so normal collagen synthesis cannot be performed.
# Causes
# Differentiating Scurvy from Other Diseases
- Advanced age
- Alcoholism
- Mental illness
- Infant on processed milk without supplementation
- Unusual diet habits
- Osteoporosis
- Idiopathic transient osteoporosis of hip
- Osteomalacia
- Osteogenesis imperfecta
- Multiple myeloma
- Homocystinuria
- Hypermetabolic resorptive osteoporosis.
# Epidemiology and Demographics
# Risk Factors
# Screening
# Natural History, Complications, and Prognosis
## Natural History
## complications
## Prognosis
Untreated scurvy is invariably fatal. However, since all that is required for a full recovery is the resumption of normal vitamin C intake, death from scurvy is rare in modern times.
# Diagnosis
## Diagnostic Criteria
# History and Symptoms
- Dark purplish spots on skin, especially legs.
- spongy gums, often leading to tooth loss.
- bleeding from all mucous membranes.
- Pallor.
- Bleeding gums.
- Sunken eyes
- Opening of healed scars and separation of knitted bone fractures.
## Physical Examination
## Laboratory Findings
## Imaging Findings
## Other Diagnostic Studies
# Treatment
## Medical Therapy
## Surgery
## Prevention
Scurvy can be prevented by a diet that includes certain citrus fruits such as oranges or lemons. Other good sources of vitamin C are fruits such as blackcurrants, guava, kiwi, papaya, tomatoes and strawberries. It can also be found in some vegetables, such as bell peppers, broccoli, potatoes, cabbage, spinach and paprika, as well as some pickled vegetables. Though redundant in the presence of a balanced diet,[9] various nutritional supplements are available that provide ascorbic acid well in excess of that required to prevent scurvy,[10] and even some candies contain vitamin C.[11] | https://www.wikidoc.org/index.php/Ascorbic_acid_deficiency | |
c705f498fe0f57262afa4cb69d34e1c51acac3f2 | wikidoc | Plaque | Plaque
Please Take Over This Page and Apply to be Editor-In-Chief for this topic:
There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Plaque or placque may refer to:
In biology:
- Dental plaque, a biofilm that builds up on teeth
- Atheromatous plaque, a buildup of fatty deposits within the wall of a blood vessel
- Mucoid plaque, a supposed thick coating of abnormal mucous material in the colon
- Viral plaque, a visible structure formed by virus propagation within a cell culture
- Senile plaques, an extracellular protein buildup implicated in various diseases like Alzheimer's disease or Parkinson's disease
- Plaque, a (usually) small, disk-shaped growth, common in some forms of skin cancer
- Pleural plaque, pleural fibrosis, often caused by exposure to asbestos
zh-min-nan:Khí-khún-pan
de:Plaque
nl:Plaque
simple:Plaque | Plaque
Please Take Over This Page and Apply to be Editor-In-Chief for this topic:
There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Plaque or placque may refer to:
In biology:
- Dental plaque, a biofilm that builds up on teeth
- Atheromatous plaque, a buildup of fatty deposits within the wall of a blood vessel
- Mucoid plaque, a supposed thick coating of abnormal mucous material in the colon
- Viral plaque, a visible structure formed by virus propagation within a cell culture
- Senile plaques, an extracellular protein buildup implicated in various diseases like Alzheimer's disease or Parkinson's disease
- Plaque, a (usually) small, disk-shaped growth, common in some forms of skin cancer
- Pleural plaque, pleural fibrosis, often caused by exposure to asbestos
Template:SIB
zh-min-nan:Khí-khún-pan
de:Plaque
nl:Plaque
simple:Plaque
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Atheromatous_plaque | |
2785debe6dc11ee67e96460d931d6e85f55b49f2 | wikidoc | Atypia | Atypia
# Overview
Atypia is a clinical term for abnormality in a cell. The term is medical jargon for an atypical cell. It may or may not be a precancerous indication associated with later malignancy, but the level of appropriate concern is highly dependent on the context with which it is diagnosed.
Atypia can be caused by an infection or irritation if diagnosed in a Pap smear, for example. In the uterus it is more likely to be precancerous.
The term atypia is also used dermatoligically and can be a precursor to melanoma.
A dermatological pathology report may show normal (junctional, compound, or intradermal) nevi, various levels of atypia (slight, moderate, severe), or melanoma. Atypia in this context is a precursor to melanoma, but is not yet melanoma.
If a mole shows slight or moderate atypia and margins are clear, no further treatment is typically needed. It would be wise to re-examine if pigmentation recurs after excision. If a mole shows slight or moderate atypia and margins are not clear, it is typical to re-excise or re-shave to get around the lesion.
If a mole shows marked or severe atypia or any degree of pathologist's concern for melanoma, it would be wise to seek professionals for further evaluation. | Atypia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Atypia is a clinical term for abnormality in a cell. The term is medical jargon for an atypical cell. It may or may not be a precancerous indication associated with later malignancy, but the level of appropriate concern is highly dependent on the context with which it is diagnosed.
Atypia can be caused by an infection or irritation if diagnosed in a Pap smear, for example. In the uterus it is more likely to be precancerous.
The term atypia is also used dermatoligically and can be a precursor to melanoma.
A dermatological pathology report may show normal (junctional, compound, or intradermal) nevi, various levels of atypia (slight, moderate, severe), or melanoma. Atypia in this context is a precursor to melanoma, but is not yet melanoma.
If a mole shows slight or moderate atypia and margins are clear, no further treatment is typically needed. It would be wise to re-examine if pigmentation recurs after excision. If a mole shows slight or moderate atypia and margins are not clear, it is typical to re-excise or re-shave to get around the lesion.
If a mole shows marked or severe atypia or any degree of pathologist's concern for melanoma, it would be wise to seek professionals for further evaluation.
Template:WS | https://www.wikidoc.org/index.php/Atypia | |
8aa06addd241be95f8c93d7bdf9cc8072af024bd | wikidoc | Avidin | Avidin
# Overview
Avidin is a glycoprotein found in the egg white and tissues of birds, reptiles and amphibians. It contains four identical subunits having a combined mass of 67,000-68,000 daltons. Each subunit consists of 128 amino acids and binds one molecule of biotin. The extent of glycosylation is very high. Carbohydrate accounts for about 10% of the total mass of avidin. Avidin has a basic isoelectric point (pI) of 10-10.5 and is stable over a wide range of pH and temperature. Extensive chemical modification has little effect on the activity of avidin, making it especially useful for protein purification. Because of its carbohydrate content and basic pI, avidin has relatively high nonspecific binding.
# Relationship between avidin and biotin
Avidin has a very strong affinity for biotin with a KD (dissociation constant) of approximately 10-15 M-1, the highest known affinity between any protein and its ligand, and, as such, prevents biotin absorption in the gastrointestinal tract. In biochemical applications, streptavidin or NeutrAvidin, which also bind very tightly to Biotin, are often used in place of avidin.
Avidin's affinity for biotin is exploited in wide ranging biochemical assays, including western blot, ELISA, ELISPOT and pull-down assays. Avidin immobilized onto solid supports is also used as purification media to capture biotin-labelled protein or nucleic acid molecules. For example, cell surface proteins can be specifically labelled with membrane impermeable biotin reagent, then specifically captured using an avidin-based support. | Avidin
# Overview
Avidin is a glycoprotein found in the egg white and tissues of birds, reptiles and amphibians. It contains four identical subunits having a combined mass of 67,000-68,000 daltons. Each subunit consists of 128 amino acids and binds one molecule of biotin. The extent of glycosylation is very high. Carbohydrate accounts for about 10% of the total mass of avidin. Avidin has a basic isoelectric point (pI) of 10-10.5 and is stable over a wide range of pH and temperature. Extensive chemical modification has little effect on the activity of avidin, making it especially useful for protein purification. Because of its carbohydrate content and basic pI, avidin has relatively high nonspecific binding.
# Relationship between avidin and biotin
Avidin has a very strong affinity for biotin with a KD (dissociation constant) of approximately 10-15 M-1[1], the highest known affinity between any protein and its ligand, and, as such, prevents biotin absorption in the gastrointestinal tract. In biochemical applications, streptavidin or NeutrAvidin, which also bind very tightly to Biotin, are often used in place of avidin.
Avidin's affinity for biotin is exploited in wide ranging biochemical assays, including western blot, ELISA, ELISPOT and pull-down assays. Avidin immobilized onto solid supports is also used as purification media to capture biotin-labelled protein or nucleic acid molecules. For example, cell surface proteins can be specifically labelled with membrane impermeable biotin reagent, then specifically captured using an avidin-based support. | https://www.wikidoc.org/index.php/Avidin | |
54e720b815b67c694ca864fcf3a349a3cae31c28 | wikidoc | Axenic | Axenic
In biology, axenic describes a culture of a particular organism that is entirely free of all other "contaminating" organisms. The earliest axenic cultures were of bacteria or unicellular eukaryotes, but axenic cultures of many multicellular organisms are also possible. Axenic cultures are useful because all of the organisms present within them are identical or share the same gene pool. Consequently they will generally respond in a more uniform and reproducible fashion, simplifying the interpretation of experiments.
Axenic cultures of microorganisms are typically prepared using a dilution series of an existing mixed culture. This culture is successively diluted to the point where subsamples of it contain only a few individual organisms, ideally only a single individual (in the case of an asexual species). These subcultures are allowed to grow until the identity of their constituent organisms can be ascertained. Selection of only those cultures consisting of the desired type of organism produces the axenic culture. Subcultures that originate from a single organism or cell without genetic change are considered clones.
Axenic cultures are usually checked routinely to ensure that they remain axenic. One standard approach with microorganisms is to spread a sample of the culture onto an agar plate, and to incubate this for a fixed period of time. The agar should be an enriched medium that will support the growth of common "contaminating" organisms. Such "contaminating" organisms will grow on the plate during this period, identifying cultures that are no longer axenic. | Axenic
In biology, axenic describes a culture of a particular organism that is entirely free of all other "contaminating" organisms. The earliest axenic cultures were of bacteria or unicellular eukaryotes, but axenic cultures of many multicellular organisms are also possible.[1] Axenic cultures are useful because all of the organisms present within them are identical or share the same gene pool. Consequently they will generally respond in a more uniform and reproducible fashion, simplifying the interpretation of experiments.
Axenic cultures of microorganisms are typically prepared using a dilution series of an existing mixed culture. This culture is successively diluted to the point where subsamples of it contain only a few individual organisms, ideally only a single individual (in the case of an asexual species). These subcultures are allowed to grow until the identity of their constituent organisms can be ascertained. Selection of only those cultures consisting of the desired type of organism produces the axenic culture. Subcultures that originate from a single organism or cell without genetic change are considered clones.
Axenic cultures are usually checked routinely to ensure that they remain axenic. One standard approach with microorganisms is to spread a sample of the culture onto an agar plate, and to incubate this for a fixed period of time. The agar should be an enriched medium that will support the growth of common "contaminating" organisms. Such "contaminating" organisms will grow on the plate during this period, identifying cultures that are no longer axenic. | https://www.wikidoc.org/index.php/Axenic | |
604c82df7e538e7441f59a56dfa2443406dc8341 | wikidoc | B cell | B cell
# Overview
B cells are lymphocytes that play a large role in the humoral immune response as opposed to the cell-mediated immune response that is governed by T cells.
B cells are produced in the bone marrow of most mammals and are therefore called B cells. The principal function of B cells is to make antibodies against soluble antigens. B cells are an essential component of the adaptive immune system.
# Development of B cells
B cells are produced in the bone marrow of most mammals. Rabbits are an exception; their B cells develop in the appendix-sacculus rotundus. B cell development occurs through several stages, each stage representing a change in the genome content at the antibody loci. An antibody is composed of two light (L) and two heavy (H) chains, and the genes specifying them are found in the 'H' chain locus and the 'L' chain locus. In the H chain loci there are three regions, V, D and J, which recombine randomly, in a process called VDJ recombination, to produce a unique variable domain in the immunoglobulin of each individual B cell. Similar rearrangements occur for L chain locus except there are only two regions, namely V and J. The list below describes the process of immunoglobulin formation at the different stages of B cell development.
- Progenitor B cells - Contains Germline H genes, Germline L genes
- Early Pro-B cells - undergoes D-J rearrangement on the H chains
- Late Pro-B cells - undergoes V-DJ rearrangement on the H chains
- Large Pre-B cells - the H chain is VDJ rearranged, Germline L genes
- Small Pre-B cells - undergoes V-J rearrangement on the L chains
- Immature B cells - VJ rearranged on L chains, VDJ rearranged on H chains. There is start of expression of IgM receptors.
- Mature B cells - There is start of expression of IgD
When the B cell fails in any step of the maturation process, it will die by a mechanism called apoptosis. If it recognizes self-antigen during the maturation process, the B cell will become suppressed (known as anergy) or undergo apoptosis (a process called negative selection). B cells are continuously produced in the bone marrow, but only a small portion of newly made B cells survive to participate in the long-lived peripheral B cell pool.
B cell membrane receptors on which drugs may be active evolve during the B cell life span . CD20 is present on preB cells, but disappears in mature B cells. TACI, BCMA and BAFF-R are present on immature B cells and mature B cells. The agonist of these 3 receptors is inhibited by Belimumab
# Functions
The human body makes millions of different types of B cells each day that circulate in the blood and lymph performing the role of immune surveillence. They do not produce antibodies until they become fully activated. Each B cell has a unique receptor protein (referred to as the B cell receptor (BCR)) on its surface that will bind to one particular antigen. The BCR is a membrane-bound immunoglobulin, and it is this molecule that allows the distinction of B cells from other types of lymphocyte, as well as being the main protein involved in B cell activation. Once a B cell encounters its cognate antigen and receives an additional signal from a T helper cell, it can further differentiate into one of the two types of B cells listed below. The B cell may either become one of these cell types directly or it may undergo an intermediate differentiation step, the germinal center reaction, where the B cell will hypermutate the variable region of its immunoglobulin gene ("somatic hypermutation") and possibly undergo class switching.
## B cell types
- Plasma B cells (also known as plasma cells) are large B cells that have been exposed to antigen and are producing and secreting large amounts of antibodies, which assist in the destruction of microbes by binding to them and making them easier targets for phagocytes and activation of the complement system. They are sometimes referred to as antibody factories. An electron micrograph of these cells reveals large amounts of rough endoplasmic reticulum, responsible for synthesizing the antibody, in the cell's cytoplasm.
- Memory B cells are formed from activated B cells that are specific to the antigen encountered during the primary immune response. These cells are able to live for a long time, and can respond quickly following a second exposure to the same antigen.
- B-1 cells express IgM in greater quantities than IgG and its receptors show polyspecificity, meaning that they have low affinities for many different antigens, but have a preference for other immunoglobulins, self antigens and common bacterial polysaccharides. B-1 cells are present in low numbers in the lymph nodes and spleen and are instead found predominantly in the peritoneal and pleural cavities.
- B-2 cells are the conventional B cells most texts refer to.
# Recognition of antigen by B cells
A critical difference between B cells and T cells is how each lymphocyte "sees" its antigen. B cells recognize their cognate antigen in its native form. They recognize free (soluble) antigen in the blood or lymph using their BCR or membrane bound-immunoglobulin. In contrast, T cells recognize their cognate antigen in a processed form, as a peptide fragment presented by an antigen presenting cell's MHC molecule to the T cell receptor.
# Activation of B cells
B cell recognition of antigen is not the only element necessary for B cell activation (a combination of clonal proliferation and terminal differentiation into plasma cells).
B cells that have not been exposed to antigen, also known as Naive B cells, can be activated in a T-cell dependent or independent manner.
## T-cell dependent activation
When a B cell ingests a pathogen, it attaches parts of the pathogen's proteins to a class II MHC protein. This complex is moved to the outside of the cell membrane, where it can be recognized by a T lymphocyte, which is compatible with similar structures on the cell membrane of a B lymphocyte. If the B cell and T cell structures match, the T lymphocyte activates the B lymphocyte, which produces antibodies against the bits of pathogen, called antigen, it has presented on its surface.
Most antigens are T-dependent, meaning T cell help is required for maximal antibody production. With a T-dependent antigen, the first signal comes from antigen cross linking the B cell receptor (BCR) and the second signal comes from co-stimulation provided by a T cell. T dependent antigens contain proteins that are presented on B cell Class II MHC to a special subtype of T cell called a Th2 cell. When a B cell processes and presents the same antigen to the primed Th cell, the T cell secretes cytokines that activate the B cell. These cytokines trigger B cell proliferation and differentiation into plasma cells. Isotype switching to IgG, IgA, and IgE and memory cell generation occur in response to T-dependent antigens. This isotype switching is known as Class Switch Recombination (CSR). Once this switch has occurred, that particular B-cell can no longer make the earlier isotypes, IgM or IgD.
## T-cell independent activation
Many antigens are T-independent, meaning they can deliver both of the signals to the B cell. Mice without a thymus (nude or athymic mice that do not produce any T cells) can respond to T-independent antigens. Many bacteria have repeating carbohydrate epitopes that stimulate B cells, through so called pattern recognition receptors, to respond with IgM synthesis in the absence of T cell help. There are two types of T-cell independent activation; Type 1 T cell-independent (polyclonal) activation, and type 2 T cell-independent activation (in which macrophages present several of the same antigen in a way that causes cross-linking of antibodies on the surface of B cells).
# The ancestral roots of B cells
In an October 2006 issue of Nature Immunology, it was reported that certain B-cells of primitive vertebrates (like fish and amphibians) are capable of phagocytosis, a function usually associated with cells of the innate immune system. The authors of this article postulate that these phagocytic B-cells represent the ancestral history shared between macrophages and lymphocytes; B-cells may have evolved from macrophage-like cells during the formation of the adaptive immune system.
B cells in humans (and other vertebrates) are nevertheless able to endocytose antibody-fixed pathogens, and it is through this route that MHC Class II presentation by B cells is possible, allowing Th2 help and stimulation of B cell proliferation. This is purely for the benefit of MHC Class II presentation, not as a significant method of reducing the pathogen load.
# Origin of the word B-cell
The abbreviation "B" in B cell originally came from Bursa of Fabricius, an organ in birds in which avian B cells mature. When it was discovered that in most mammals B cells are formed in bone marrow, the word B cell continued to be appropriate. The fact that bone and bursa both start with the letter 'B' is a coincidence. | B cell
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
B cells are lymphocytes that play a large role in the humoral immune response as opposed to the cell-mediated immune response that is governed by T cells.
B cells are produced in the bone marrow of most mammals and are therefore called B cells. The principal function of B cells is to make antibodies against soluble antigens. B cells are an essential component of the adaptive immune system.
# Development of B cells
B cells are produced in the bone marrow of most mammals. Rabbits are an exception; their B cells develop in the appendix-sacculus rotundus. B cell development occurs through several stages, each stage representing a change in the genome content at the antibody loci. An antibody is composed of two light (L) and two heavy (H) chains, and the genes specifying them are found in the 'H' chain locus and the 'L' chain locus. In the H chain loci there are three regions, V, D and J, which recombine randomly, in a process called VDJ recombination, to produce a unique variable domain in the immunoglobulin of each individual B cell. Similar rearrangements occur for L chain locus except there are only two regions, namely V and J. The list below describes the process of immunoglobulin formation at the different stages of B cell development.
- Progenitor B cells - Contains Germline H genes, Germline L genes
- Early Pro-B cells - undergoes D-J rearrangement on the H chains
- Late Pro-B cells - undergoes V-DJ rearrangement on the H chains
- Large Pre-B cells - the H chain is VDJ rearranged, Germline L genes
- Small Pre-B cells - undergoes V-J rearrangement on the L chains
- Immature B cells - VJ rearranged on L chains, VDJ rearranged on H chains. There is start of expression of IgM receptors.
- Mature B cells - There is start of expression of IgD
When the B cell fails in any step of the maturation process, it will die by a mechanism called apoptosis. If it recognizes self-antigen during the maturation process, the B cell will become suppressed (known as anergy) or undergo apoptosis (a process called negative selection). B cells are continuously produced in the bone marrow, but only a small portion of newly made B cells survive to participate in the long-lived peripheral B cell pool.
B cell membrane receptors on which drugs may be active evolve during the B cell life span [2]. CD20 is present on preB cells, but disappears in mature B cells. TACI, BCMA and BAFF-R are present on immature B cells and mature B cells. The agonist of these 3 receptors is inhibited by Belimumab
# Functions
The human body makes millions of different types of B cells each day that circulate in the blood and lymph performing the role of immune surveillence. They do not produce antibodies until they become fully activated. Each B cell has a unique receptor protein (referred to as the B cell receptor (BCR)) on its surface that will bind to one particular antigen. The BCR is a membrane-bound immunoglobulin, and it is this molecule that allows the distinction of B cells from other types of lymphocyte, as well as being the main protein involved in B cell activation. Once a B cell encounters its cognate antigen and receives an additional signal from a T helper cell, it can further differentiate into one of the two types of B cells listed below. The B cell may either become one of these cell types directly or it may undergo an intermediate differentiation step, the germinal center reaction, where the B cell will hypermutate the variable region of its immunoglobulin gene ("somatic hypermutation") and possibly undergo class switching.
## B cell types
- Plasma B cells (also known as plasma cells) are large B cells that have been exposed to antigen and are producing and secreting large amounts of antibodies, which assist in the destruction of microbes by binding to them and making them easier targets for phagocytes and activation of the complement system. They are sometimes referred to as antibody factories. An electron micrograph of these cells reveals large amounts of rough endoplasmic reticulum, responsible for synthesizing the antibody, in the cell's cytoplasm.
- Memory B cells are formed from activated B cells that are specific to the antigen encountered during the primary immune response. These cells are able to live for a long time, and can respond quickly following a second exposure to the same antigen.
- B-1 cells express IgM in greater quantities than IgG and its receptors show polyspecificity, meaning that they have low affinities for many different antigens, but have a preference for other immunoglobulins, self antigens and common bacterial polysaccharides. B-1 cells are present in low numbers in the lymph nodes and spleen and are instead found predominantly in the peritoneal and pleural cavities.
- B-2 cells are the conventional B cells most texts refer to.
# Recognition of antigen by B cells
A critical difference between B cells and T cells is how each lymphocyte "sees" its antigen. B cells recognize their cognate antigen in its native form. They recognize free (soluble) antigen in the blood or lymph using their BCR or membrane bound-immunoglobulin. In contrast, T cells recognize their cognate antigen in a processed form, as a peptide fragment presented by an antigen presenting cell's MHC molecule to the T cell receptor.
# Activation of B cells
B cell recognition of antigen is not the only element necessary for B cell activation (a combination of clonal proliferation and terminal differentiation into plasma cells).
B cells that have not been exposed to antigen, also known as Naive B cells, can be activated in a T-cell dependent or independent manner.
## T-cell dependent activation
When a B cell ingests a pathogen, it attaches parts of the pathogen's proteins to a class II MHC protein. This complex is moved to the outside of the cell membrane, where it can be recognized by a T lymphocyte, which is compatible with similar structures on the cell membrane of a B lymphocyte. If the B cell and T cell structures match, the T lymphocyte activates the B lymphocyte, which produces antibodies against the bits of pathogen, called antigen, it has presented on its surface.
Most antigens are T-dependent, meaning T cell help is required for maximal antibody production. With a T-dependent antigen, the first signal comes from antigen cross linking the B cell receptor (BCR) and the second signal comes from co-stimulation provided by a T cell. T dependent antigens contain proteins that are presented on B cell Class II MHC to a special subtype of T cell called a Th2 cell. When a B cell processes and presents the same antigen to the primed Th cell, the T cell secretes cytokines that activate the B cell. These cytokines trigger B cell proliferation and differentiation into plasma cells. Isotype switching to IgG, IgA, and IgE and memory cell generation occur in response to T-dependent antigens. This isotype switching is known as Class Switch Recombination (CSR). Once this switch has occurred, that particular B-cell can no longer make the earlier isotypes, IgM or IgD.
## T-cell independent activation
Many antigens are T-independent, meaning they can deliver both of the signals to the B cell. Mice without a thymus (nude or athymic mice that do not produce any T cells) can respond to T-independent antigens. Many bacteria have repeating carbohydrate epitopes that stimulate B cells, through so called pattern recognition receptors, to respond with IgM synthesis in the absence of T cell help. There are two types of T-cell independent activation; Type 1 T cell-independent (polyclonal) activation, and type 2 T cell-independent activation (in which macrophages present several of the same antigen in a way that causes cross-linking of antibodies on the surface of B cells).
# The ancestral roots of B cells
In an October 2006 issue of Nature Immunology, it was reported that certain B-cells of primitive vertebrates (like fish and amphibians) are capable of phagocytosis, a function usually associated with cells of the innate immune system. The authors of this article postulate that these phagocytic B-cells represent the ancestral history shared between macrophages and lymphocytes; B-cells may have evolved from macrophage-like cells during the formation of the adaptive immune system[1].
B cells in humans (and other vertebrates) are nevertheless able to endocytose antibody-fixed pathogens, and it is through this route that MHC Class II presentation by B cells is possible, allowing Th2 help and stimulation of B cell proliferation. This is purely for the benefit of MHC Class II presentation, not as a significant method of reducing the pathogen load.
# Origin of the word B-cell
The abbreviation "B" in B cell originally came from Bursa of Fabricius, an organ in birds in which avian B cells mature. When it was discovered that in most mammals B cells are formed in bone marrow, the word B cell continued to be appropriate. The fact that bone and bursa both start with the letter 'B' is a coincidence. | https://www.wikidoc.org/index.php/B-Cells | |
0989aaf49525455ea27de1411e8cea7e8bf0a8a0 | wikidoc | B3GAT1 | B3GAT1
Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 (B3GAT1) is an enzyme that in humans is encoded by the B3GAT1 gene, whose enzymatic activity creates the CD57 epitope on other cell surface proteins. In immunology, the CD57 antigen (CD stands for cluster of differentiation) is also known as HNK1 (human natural killer-1) or LEU7. It is expressed as a carbohydrate epitope that contains a sulfoglucuronyl residue in several adhesion molecules of the nervous system.
# Function
The protein encoded by this gene is a member of the glucuronyltransferase gene family. These enzymes exhibit strict acceptor specificity, recognizing nonreducing terminal sugars and their anomeric linkages. This gene product functions as the key enzyme in a glucuronyl transfer reaction during the biosynthesis of the carbohydrate epitope HNK-1 (human natural killer-1, also known as CD57 and LEU7). Alternate transcriptional splice variants have been characterized.
# Immunohistochemistry
In anatomical pathology, CD57 (immunostaining) is similar to CD56 for use in differentiating neuroendocrine tumors from others. Using immunohistochemistry, CD57 molecule can be demonstrated in around 10 to 20% of lymphocytes, as well as in some epithelial, neural, and chromaffin cells. Among lymphocytes, CD57 positive cells are typically either T cells or NK cells, and are most commonly found within the germinal centres of lymph nodes, tonsils, and the spleen.
There is an increase in the number of circulating CD57 positive cells in the blood of patients who have recently undergone organ or tissue transplants, especially of the bone marrow, and in patients with HIV. Increased CD57+ counts have also been reported in rheumatoid arthritis and Felty's syndrome, among other conditions.
Neoplastic CD57 positive cells are seen in conditions as varied as large granular lymphocytic leukaemia, small-cell carcinoma, thyroid carcinoma, and neural and carcinoid tumours. Although the antigen is particularly common in carcinoid tumours, it is found in such a wide range of other conditions that it is of less use in distinguishing these tumours from others than more specific markers such as chromogranin and NSE. | B3GAT1
Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 (B3GAT1) is an enzyme that in humans is encoded by the B3GAT1 gene, whose enzymatic activity creates the CD57 epitope on other cell surface proteins.[1] In immunology, the CD57 antigen (CD stands for cluster of differentiation) is also known as HNK1 (human natural killer-1) or LEU7. It is expressed as a carbohydrate epitope that contains a sulfoglucuronyl residue in several adhesion molecules of the nervous system.[2]
# Function
The protein encoded by this gene is a member of the glucuronyltransferase gene family. These enzymes exhibit strict acceptor specificity, recognizing nonreducing terminal sugars and their anomeric linkages. This gene product functions as the key enzyme in a glucuronyl transfer reaction during the biosynthesis of the carbohydrate epitope HNK-1 (human natural killer-1, also known as CD57 and LEU7). Alternate transcriptional splice variants have been characterized.[1]
# Immunohistochemistry
In anatomical pathology, CD57 (immunostaining) is similar to CD56 for use in differentiating neuroendocrine tumors from others.[3] Using immunohistochemistry, CD57 molecule can be demonstrated in around 10 to 20% of lymphocytes, as well as in some epithelial, neural, and chromaffin cells. Among lymphocytes, CD57 positive cells are typically either T cells or NK cells, and are most commonly found within the germinal centres of lymph nodes, tonsils, and the spleen.[4]
There is an increase in the number of circulating CD57 positive cells in the blood of patients who have recently undergone organ or tissue transplants, especially of the bone marrow, and in patients with HIV. Increased CD57+ counts have also been reported in rheumatoid arthritis and Felty's syndrome, among other conditions.[4]
Neoplastic CD57 positive cells are seen in conditions as varied as large granular lymphocytic leukaemia, small-cell carcinoma, thyroid carcinoma, and neural and carcinoid tumours. Although the antigen is particularly common in carcinoid tumours, it is found in such a wide range of other conditions that it is of less use in distinguishing these tumours from others than more specific markers such as chromogranin and NSE.[4] | https://www.wikidoc.org/index.php/B3GAT1 | |
3186dd3499922153dea9a3e3783d83f3c8e8b979 | wikidoc | B3GAT2 | B3GAT2
Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 is an enzyme that in humans is encoded by the B3GAT2 gene.
The product of this gene is a transmembrane protein belonging to the glucuronyltransferase family, and catalyzes the transfer of a beta-1,3 linked glucuronic acid to a terminal galactose in different glycoproteins or glycolipids containing a Gal-beta-1-4GlcNAc or Gal-beta-1-3GlcNAc residue. The encoded protein is involved in the synthesis of the human natural killer-1 (HNK-1) carbohydrate epitope, a sulfated trisaccharide implicated in cellular migration and adhesion in the nervous system.
# Use of HNK-1 Antibody for Neural Crest Research
Antibodies raised against the HNK-1 epitope have played a large role in studies of the neural crest, especially in the avian embryo. The first antibody raised against this epitope was NC-1, which permitted much easier analyses of neural crest migration pathways. In avians, and especially in other vertebrates, the results of HNK-1 staining should be interpreted with caution as the epitope is not unique to the neural crest. | B3GAT2
Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 is an enzyme that in humans is encoded by the B3GAT2 gene.[1][2]
The product of this gene is a transmembrane protein belonging to the glucuronyltransferase family, and catalyzes the transfer of a beta-1,3 linked glucuronic acid to a terminal galactose in different glycoproteins or glycolipids containing a Gal-beta-1-4GlcNAc or Gal-beta-1-3GlcNAc residue. The encoded protein is involved in the synthesis of the human natural killer-1 (HNK-1) carbohydrate epitope, a sulfated trisaccharide implicated in cellular migration and adhesion in the nervous system.[2]
# Use of HNK-1 Antibody for Neural Crest Research
Antibodies raised against the HNK-1 epitope have played a large role in studies of the neural crest, especially in the avian embryo.[3] The first antibody raised against this epitope was NC-1,[4] which permitted much easier analyses of neural crest migration pathways. In avians, and especially in other vertebrates, the results of HNK-1 staining should be interpreted with caution as the epitope is not unique to the neural crest. | https://www.wikidoc.org/index.php/B3GAT2 |
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