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Biochemistry_Lippincott_283	Biochemistry_Lippinco	A. Isomers and epimers Compounds that have the same chemical formula but have different structures are called isomers. For example, fructose, glucose, mannose, and galactose are all isomers of each other, having the same chemical formula, C6H12O6. Carbohydrate isomers that differ in configuration around only one specific carbon atom (with the exception of the carbonyl carbon, see C. 1. below) are defined as epimers of each other. For example, glucose and galactose are C-4 epimers because their structures differ only in the position of the –OH (hydroxyl) group at carbon 4. [Note: The carbons in sugars are numbered beginning at the end that contains the carbonyl carbon (that is, the aldehyde or keto group), as shown in Fig. 7.4.] Glucose and mannose are C-2 epimers. However, because galactose and mannose differ in the position of –OH groups at two carbons (carbons 2 and 4), they are isomers rather than epimers (see Fig. 7.4). B. Enantiomers	Biochemistry_Lippinco. A. Isomers and epimers Compounds that have the same chemical formula but have different structures are called isomers. For example, fructose, glucose, mannose, and galactose are all isomers of each other, having the same chemical formula, C6H12O6. Carbohydrate isomers that differ in configuration around only one specific carbon atom (with the exception of the carbonyl carbon, see C. 1. below) are defined as epimers of each other. For example, glucose and galactose are C-4 epimers because their structures differ only in the position of the –OH (hydroxyl) group at carbon 4. [Note: The carbons in sugars are numbered beginning at the end that contains the carbonyl carbon (that is, the aldehyde or keto group), as shown in Fig. 7.4.] Glucose and mannose are C-2 epimers. However, because galactose and mannose differ in the position of –OH groups at two carbons (carbons 2 and 4), they are isomers rather than epimers (see Fig. 7.4). B. Enantiomers
Biochemistry_Lippincott_284	Biochemistry_Lippinco	B. Enantiomers A special type of isomerism is found in the pairs of structures that are mirror images of each other. These mirror images are called enantiomers, and the two members of the pair are designated as a D-and an L-sugar (Fig. 7.5). The vast majority of the sugars in humans are D-isomers. In the D-isomeric form, the –OH group on the asymmetric carbon (a carbon linked to four different atoms or groups) farthest from the carbonyl carbon is on the right, whereas in the L-isomer, it is on the left. Most enzymes are specific for either the D or the L form, but enzymes known as isomerases are able to interconvert D-and L-isomers. comparison to a triose, glyceraldehyde. [Note: The asymmetric carbons are shown in green.] C. Monosaccharide cyclization	Biochemistry_Lippinco. B. Enantiomers A special type of isomerism is found in the pairs of structures that are mirror images of each other. These mirror images are called enantiomers, and the two members of the pair are designated as a D-and an L-sugar (Fig. 7.5). The vast majority of the sugars in humans are D-isomers. In the D-isomeric form, the –OH group on the asymmetric carbon (a carbon linked to four different atoms or groups) farthest from the carbonyl carbon is on the right, whereas in the L-isomer, it is on the left. Most enzymes are specific for either the D or the L form, but enzymes known as isomerases are able to interconvert D-and L-isomers. comparison to a triose, glyceraldehyde. [Note: The asymmetric carbons are shown in green.] C. Monosaccharide cyclization
Biochemistry_Lippincott_285	Biochemistry_Lippinco	comparison to a triose, glyceraldehyde. [Note: The asymmetric carbons are shown in green.] C. Monosaccharide cyclization Less than 1% of each of the monosaccharides with five or more carbons exists in the open-chain (acyclic) form in solution. Rather, they are predominantly found in a ring (cyclic) form, in which the aldehyde (or keto) group has reacted with a hydroxyl group on the same sugar, making the carbonyl carbon (carbon 1 for an aldose, carbon 2 for a ketose) asymmetric. This asymmetric carbon is referred to as the anomeric carbon.	Biochemistry_Lippinco. comparison to a triose, glyceraldehyde. [Note: The asymmetric carbons are shown in green.] C. Monosaccharide cyclization Less than 1% of each of the monosaccharides with five or more carbons exists in the open-chain (acyclic) form in solution. Rather, they are predominantly found in a ring (cyclic) form, in which the aldehyde (or keto) group has reacted with a hydroxyl group on the same sugar, making the carbonyl carbon (carbon 1 for an aldose, carbon 2 for a ketose) asymmetric. This asymmetric carbon is referred to as the anomeric carbon.
Biochemistry_Lippincott_286	Biochemistry_Lippinco	1. Anomers: Creation of an anomeric carbon (the former carbonyl carbon) generates a new pair of isomers, the α and β configurations of the sugar (for example, α-D-glucopyranose and β-D-glucopyranose), as shown in Figure 7.6, that are anomers of each other. [Note: In the α configuration, the –OH group on the anomeric carbon projects to the same side as the ring in a modified Fischer projection formula (see Fig. 7.6A) and is trans to the CH2OH group in a Haworth projection formula (see Fig. 7.6B).	Biochemistry_Lippinco. 1. Anomers: Creation of an anomeric carbon (the former carbonyl carbon) generates a new pair of isomers, the α and β configurations of the sugar (for example, α-D-glucopyranose and β-D-glucopyranose), as shown in Figure 7.6, that are anomers of each other. [Note: In the α configuration, the –OH group on the anomeric carbon projects to the same side as the ring in a modified Fischer projection formula (see Fig. 7.6A) and is trans to the CH2OH group in a Haworth projection formula (see Fig. 7.6B).
Biochemistry_Lippincott_287	Biochemistry_Lippinco	The α and β forms are not mirror images, and they are referred to as diastereomers.] Enzymes are able to distinguish between these two structures and use one or the other preferentially. For example, glycogen is synthesized from α-D-glucopyranose, whereas cellulose is synthesized from β-D-glucopyranose. The cyclic α and β anomers of a sugar in solution spontaneously (but slowly) form an equilibrium mixture, a process known as mutarotation (see Fig. 7.6). [Note: For glucose, the α form makes up 36% of the mixture.] six-membered ring (5 C + 1 O) is termed a pyranose, whereas one with a five-membered ring (4 C + 1 O) is a furanose. Virtually all glucose in solution is in the pyranose form.] 2. Reducing sugars: If the hydroxyl group on the anomeric carbon of a cyclized sugar is not linked to another compound by a glycosidic bond (see E. below), the ring can open. The sugar can act as a reducing agent and is termed a reducing sugar. Such sugars can react with chromogenic agents (for	Biochemistry_Lippinco. The α and β forms are not mirror images, and they are referred to as diastereomers.] Enzymes are able to distinguish between these two structures and use one or the other preferentially. For example, glycogen is synthesized from α-D-glucopyranose, whereas cellulose is synthesized from β-D-glucopyranose. The cyclic α and β anomers of a sugar in solution spontaneously (but slowly) form an equilibrium mixture, a process known as mutarotation (see Fig. 7.6). [Note: For glucose, the α form makes up 36% of the mixture.] six-membered ring (5 C + 1 O) is termed a pyranose, whereas one with a five-membered ring (4 C + 1 O) is a furanose. Virtually all glucose in solution is in the pyranose form.] 2. Reducing sugars: If the hydroxyl group on the anomeric carbon of a cyclized sugar is not linked to another compound by a glycosidic bond (see E. below), the ring can open. The sugar can act as a reducing agent and is termed a reducing sugar. Such sugars can react with chromogenic agents (for
Biochemistry_Lippincott_288	Biochemistry_Lippinco	to another compound by a glycosidic bond (see E. below), the ring can open. The sugar can act as a reducing agent and is termed a reducing sugar. Such sugars can react with chromogenic agents (for example, the Benedict reagent) causing the reagent to be reduced and colored as the aldehyde group of the acyclic sugar is oxidized to a carboxyl group. All monosaccharides, but not all disaccharides, are reducing sugars. [Note: Fructose, a ketose, is a reducing sugar because it can be isomerized to an aldose.]	Biochemistry_Lippinco. to another compound by a glycosidic bond (see E. below), the ring can open. The sugar can act as a reducing agent and is termed a reducing sugar. Such sugars can react with chromogenic agents (for example, the Benedict reagent) causing the reagent to be reduced and colored as the aldehyde group of the acyclic sugar is oxidized to a carboxyl group. All monosaccharides, but not all disaccharides, are reducing sugars. [Note: Fructose, a ketose, is a reducing sugar because it can be isomerized to an aldose.]
Biochemistry_Lippincott_289	Biochemistry_Lippinco	A colorimetric test can detect a reducing sugar in urine. A positive result is indicative of an underlying pathology (because sugars are not normally present in urine) and can be followed up by more specific tests to identify the reducing sugar. D. Monosaccharide joining Monosaccharides can be joined to form disaccharides, oligosaccharides, and polysaccharides. Important disaccharides include lactose (galactose + glucose), sucrose (glucose + fructose), and maltose (glucose + glucose). Important polysaccharides include branched glycogen (from animal sources) and starch (plant sources) and unbranched cellulose (plant sources). Each is a polymer of glucose. E. Glycosidic bonds	Biochemistry_Lippinco. A colorimetric test can detect a reducing sugar in urine. A positive result is indicative of an underlying pathology (because sugars are not normally present in urine) and can be followed up by more specific tests to identify the reducing sugar. D. Monosaccharide joining Monosaccharides can be joined to form disaccharides, oligosaccharides, and polysaccharides. Important disaccharides include lactose (galactose + glucose), sucrose (glucose + fructose), and maltose (glucose + glucose). Important polysaccharides include branched glycogen (from animal sources) and starch (plant sources) and unbranched cellulose (plant sources). Each is a polymer of glucose. E. Glycosidic bonds
Biochemistry_Lippincott_290	Biochemistry_Lippinco	E. Glycosidic bonds The bonds that link sugars are called glycosidic bonds. They are formed by enzymes known as glycosyltransferases that use nucleotide sugars (activated sugars) such as uridine diphosphate glucose as substrates. Glycosidic bonds between sugars are named according to the numbers of the connected carbons and with regard to the position of the anomeric hydroxyl group of the first sugar involved in the bond. If this anomeric hydroxyl is in the α configuration, then the linkage is an α-bond. If it is in the β configuration, then the linkage is a β-bond. Lactose, for example, is synthesized by forming a glycosidic bond between carbon 1 of β-galactose and carbon 4 of glucose. Therefore, the linkage is a β(1→4) glycosidic bond (see Fig. 7.3). [Note: Because the anomeric end of the glucose residue is not involved in the glycosidic linkage, it (and, therefore, lactose) remains a reducing sugar.] F. Carbohydrate linkage to noncarbohydrates	Biochemistry_Lippinco. E. Glycosidic bonds The bonds that link sugars are called glycosidic bonds. They are formed by enzymes known as glycosyltransferases that use nucleotide sugars (activated sugars) such as uridine diphosphate glucose as substrates. Glycosidic bonds between sugars are named according to the numbers of the connected carbons and with regard to the position of the anomeric hydroxyl group of the first sugar involved in the bond. If this anomeric hydroxyl is in the α configuration, then the linkage is an α-bond. If it is in the β configuration, then the linkage is a β-bond. Lactose, for example, is synthesized by forming a glycosidic bond between carbon 1 of β-galactose and carbon 4 of glucose. Therefore, the linkage is a β(1→4) glycosidic bond (see Fig. 7.3). [Note: Because the anomeric end of the glucose residue is not involved in the glycosidic linkage, it (and, therefore, lactose) remains a reducing sugar.] F. Carbohydrate linkage to noncarbohydrates
Biochemistry_Lippincott_291	Biochemistry_Lippinco	F. Carbohydrate linkage to noncarbohydrates Carbohydrates can be attached by glycosidic bonds to noncarbohydrate structures, including purine and pyrimidine bases (found in nucleic acids), aromatic rings (such as those found in steroids and bilirubin), proteins (found in glycoproteins and proteoglycans), and lipids (found in glycolipids). If the group on the noncarbohydrate molecule to which the sugar is attached is an –NH2 group, then the bond is called an N-glycosidic link. If the group is an –OH, then the bond is an O-glycosidic link (Fig. 7.7). [Note: All sugar-sugar glycosidic bonds are O-type linkages.] III. DIETARY CARBOHYDRATE DIGESTION	Biochemistry_Lippinco. F. Carbohydrate linkage to noncarbohydrates Carbohydrates can be attached by glycosidic bonds to noncarbohydrate structures, including purine and pyrimidine bases (found in nucleic acids), aromatic rings (such as those found in steroids and bilirubin), proteins (found in glycoproteins and proteoglycans), and lipids (found in glycolipids). If the group on the noncarbohydrate molecule to which the sugar is attached is an –NH2 group, then the bond is called an N-glycosidic link. If the group is an –OH, then the bond is an O-glycosidic link (Fig. 7.7). [Note: All sugar-sugar glycosidic bonds are O-type linkages.] III. DIETARY CARBOHYDRATE DIGESTION
Biochemistry_Lippincott_292	Biochemistry_Lippinco	III. DIETARY CARBOHYDRATE DIGESTION The principal sites of dietary carbohydrate digestion are the mouth and intestinal lumen. This digestion is rapid and is catalyzed by enzymes known as glycoside hydrolases (glycosidases) that hydrolyze glycosidic bonds (Fig. 7.8). Because little monosaccharide is present in diets of mixed animal and plant origin, the enzymes are primarily endoglycosidases that hydrolyze polysaccharides and oligosaccharides and disaccharidases that hydrolyze tri-and disaccharides into their reducing sugar components. Glycosidases are usually specific for the structure and configuration of the glycosyl residue to be removed as well as for the type of bond to be broken. The final products of carbohydrate digestion are the monosaccharides glucose, galactose, and fructose that are absorbed by cells (enterocytes) of the small intestine. A. Salivary α-amylase	Biochemistry_Lippinco. III. DIETARY CARBOHYDRATE DIGESTION The principal sites of dietary carbohydrate digestion are the mouth and intestinal lumen. This digestion is rapid and is catalyzed by enzymes known as glycoside hydrolases (glycosidases) that hydrolyze glycosidic bonds (Fig. 7.8). Because little monosaccharide is present in diets of mixed animal and plant origin, the enzymes are primarily endoglycosidases that hydrolyze polysaccharides and oligosaccharides and disaccharidases that hydrolyze tri-and disaccharides into their reducing sugar components. Glycosidases are usually specific for the structure and configuration of the glycosyl residue to be removed as well as for the type of bond to be broken. The final products of carbohydrate digestion are the monosaccharides glucose, galactose, and fructose that are absorbed by cells (enterocytes) of the small intestine. A. Salivary α-amylase
Biochemistry_Lippincott_293	Biochemistry_Lippinco	A. Salivary α-amylase The major dietary polysaccharides are of plant (starch, composed of amylose and amylopectin) and animal (glycogen) origin. During mastication (chewing), salivary α-amylase acts briefly on dietary starch and glycogen, hydrolyzing random α(1→4) bonds. [Note: There are both α(1→4)-and β(1→4)-endoglucosidases in nature, but humans do not produce the latter. Therefore, we are unable to digest cellulose, a carbohydrate of plant origin containing β(1→4) glycosidic bonds between glucose residues.] Because branched amylopectin and glycogen also contain α(1→6) bonds, which α-amylase cannot hydrolyze, the digest resulting from its action contains a mixture of short, branched and unbranched oligosaccharides known as dextrins (Fig. 7.9). [Note: Disaccharides are also present as they, too, are resistant to amylase.] Carbohydrate digestion halts temporarily in the stomach, because the high acidity inactivates salivary α-amylase. B. Pancreatic α-amylase	Biochemistry_Lippinco. A. Salivary α-amylase The major dietary polysaccharides are of plant (starch, composed of amylose and amylopectin) and animal (glycogen) origin. During mastication (chewing), salivary α-amylase acts briefly on dietary starch and glycogen, hydrolyzing random α(1→4) bonds. [Note: There are both α(1→4)-and β(1→4)-endoglucosidases in nature, but humans do not produce the latter. Therefore, we are unable to digest cellulose, a carbohydrate of plant origin containing β(1→4) glycosidic bonds between glucose residues.] Because branched amylopectin and glycogen also contain α(1→6) bonds, which α-amylase cannot hydrolyze, the digest resulting from its action contains a mixture of short, branched and unbranched oligosaccharides known as dextrins (Fig. 7.9). [Note: Disaccharides are also present as they, too, are resistant to amylase.] Carbohydrate digestion halts temporarily in the stomach, because the high acidity inactivates salivary α-amylase. B. Pancreatic α-amylase
Biochemistry_Lippincott_294	Biochemistry_Lippinco	Carbohydrate digestion halts temporarily in the stomach, because the high acidity inactivates salivary α-amylase. B. Pancreatic α-amylase When the acidic stomach contents reach the small intestine, they are neutralized by bicarbonate secreted by the pancreas, and pancreatic αamylase continues the process of starch digestion. C. Intestinal disaccharidases	Biochemistry_Lippinco. Carbohydrate digestion halts temporarily in the stomach, because the high acidity inactivates salivary α-amylase. B. Pancreatic α-amylase When the acidic stomach contents reach the small intestine, they are neutralized by bicarbonate secreted by the pancreas, and pancreatic αamylase continues the process of starch digestion. C. Intestinal disaccharidases
Biochemistry_Lippincott_295	Biochemistry_Lippinco	C. Intestinal disaccharidases The final digestive processes occur primarily at the mucosal lining of the duodenum and upper jejunum and include the action of several disaccharidases (see Fig. 7.9). For example, isomaltase cleaves the α(1→6) bond in isomaltose, and maltase cleaves the α(1→4) bond in maltose and maltotriose, each producing glucose. Sucrase cleaves the α(1→2) bond in sucrose, producing glucose and fructose, and lactase (β-galactosidase) cleaves the β(1→4) bond in lactose, producing galactose and glucose. [Note: The substrates for isomaltase are broader than its name suggests, and it hydrolyzes the majority of maltose.] Trehalose, an α(1→1) disaccharide of glucose found in mushrooms and other fungi, is cleaved by trehalase. These enzymes are transmembrane proteins of the brush border on the luminal (apical) surface of the enterocytes.	Biochemistry_Lippinco. C. Intestinal disaccharidases The final digestive processes occur primarily at the mucosal lining of the duodenum and upper jejunum and include the action of several disaccharidases (see Fig. 7.9). For example, isomaltase cleaves the α(1→6) bond in isomaltose, and maltase cleaves the α(1→4) bond in maltose and maltotriose, each producing glucose. Sucrase cleaves the α(1→2) bond in sucrose, producing glucose and fructose, and lactase (β-galactosidase) cleaves the β(1→4) bond in lactose, producing galactose and glucose. [Note: The substrates for isomaltase are broader than its name suggests, and it hydrolyzes the majority of maltose.] Trehalose, an α(1→1) disaccharide of glucose found in mushrooms and other fungi, is cleaved by trehalase. These enzymes are transmembrane proteins of the brush border on the luminal (apical) surface of the enterocytes.
Biochemistry_Lippincott_296	Biochemistry_Lippinco	Sucrase and isomaltase are enzymic activities of a single protein that is cleaved into two functional subunits, which remain associated in the cell membrane and form the sucrase-isomaltase (SI) complex. In contrast, maltase is one of two enzymic activities of the single membrane protein maltase-glucoamylase (MGA) that does not get cleaved. Its second enzymic activity, glucoamylase, cleaves α(1→4) glycosidic bonds in dextrins. D. Intestinal absorption of monosaccharides	Biochemistry_Lippinco. Sucrase and isomaltase are enzymic activities of a single protein that is cleaved into two functional subunits, which remain associated in the cell membrane and form the sucrase-isomaltase (SI) complex. In contrast, maltase is one of two enzymic activities of the single membrane protein maltase-glucoamylase (MGA) that does not get cleaved. Its second enzymic activity, glucoamylase, cleaves α(1→4) glycosidic bonds in dextrins. D. Intestinal absorption of monosaccharides
Biochemistry_Lippincott_297	Biochemistry_Lippinco	D. Intestinal absorption of monosaccharides The upper jejunum absorbs the bulk of the monosaccharide products of digestion. However, different sugars have different mechanisms of absorption (Fig. 7.10). For example, galactose and glucose are taken into enterocytes by secondary active transport that requires a concurrent uptake (symport) of sodium (Na+) ions. The transport protein is the sodium-dependent glucose cotransporter 1 (SGLT-1). [Note: Sugar transport is driven by the Na+ gradient created by the Na+-potassium (K+) ATPase that moves Na+ out of the enterocyte and K+ in (see Fig. 7.10).] Fructose absorption utilizes an energy-and Na+-independent monosaccharide transporter (GLUT-5). All three monosaccharides are transported from the enterocytes into the portal circulation by yet another transporter, GLUT-2. [Note: See p. 97 for a discussion of these transporters.] E. Abnormal degradation of disaccharides	Biochemistry_Lippinco. D. Intestinal absorption of monosaccharides The upper jejunum absorbs the bulk of the monosaccharide products of digestion. However, different sugars have different mechanisms of absorption (Fig. 7.10). For example, galactose and glucose are taken into enterocytes by secondary active transport that requires a concurrent uptake (symport) of sodium (Na+) ions. The transport protein is the sodium-dependent glucose cotransporter 1 (SGLT-1). [Note: Sugar transport is driven by the Na+ gradient created by the Na+-potassium (K+) ATPase that moves Na+ out of the enterocyte and K+ in (see Fig. 7.10).] Fructose absorption utilizes an energy-and Na+-independent monosaccharide transporter (GLUT-5). All three monosaccharides are transported from the enterocytes into the portal circulation by yet another transporter, GLUT-2. [Note: See p. 97 for a discussion of these transporters.] E. Abnormal degradation of disaccharides
Biochemistry_Lippincott_298	Biochemistry_Lippinco	E. Abnormal degradation of disaccharides The overall process of carbohydrate digestion and absorption is so efficient in healthy individuals that ordinarily all digestible dietary carbohydrate is absorbed by the time the ingested material reaches the lower jejunum. However, because only monosaccharides are absorbed, any deficiency (genetic or acquired) in a specific disaccharidase activity of the intestinal mucosa causes the passage of undigested carbohydrate into the large intestine. As a consequence of the presence of this osmotically active material, water is drawn from the mucosa into the large intestine, causing osmotic diarrhea. This is reinforced by the bacterial fermentation of the remaining carbohydrate to two-and three-carbon compounds (which are also osmotically active) plus large volumes of carbon dioxide and hydrogen gas (H2), causing abdominal cramps, diarrhea, and flatulence. 1.	Biochemistry_Lippinco. E. Abnormal degradation of disaccharides The overall process of carbohydrate digestion and absorption is so efficient in healthy individuals that ordinarily all digestible dietary carbohydrate is absorbed by the time the ingested material reaches the lower jejunum. However, because only monosaccharides are absorbed, any deficiency (genetic or acquired) in a specific disaccharidase activity of the intestinal mucosa causes the passage of undigested carbohydrate into the large intestine. As a consequence of the presence of this osmotically active material, water is drawn from the mucosa into the large intestine, causing osmotic diarrhea. This is reinforced by the bacterial fermentation of the remaining carbohydrate to two-and three-carbon compounds (which are also osmotically active) plus large volumes of carbon dioxide and hydrogen gas (H2), causing abdominal cramps, diarrhea, and flatulence. 1.
Biochemistry_Lippincott_299	Biochemistry_Lippinco	1. Digestive enzyme deficiencies: Genetic deficiencies of the individual disaccharidases result in disaccharide intolerance. Alterations in disaccharide degradation can also be caused by a variety of intestinal diseases, malnutrition, and drugs that injure the mucosa of the small intestine. For example, brush border enzymes are rapidly lost in normal individuals with severe diarrhea, causing a temporary, acquired enzyme deficiency. Therefore, patients suffering or recovering from such a disorder cannot drink or eat significant amounts of dairy products or sucrose without exacerbating the diarrhea. 2.	Biochemistry_Lippinco. 1. Digestive enzyme deficiencies: Genetic deficiencies of the individual disaccharidases result in disaccharide intolerance. Alterations in disaccharide degradation can also be caused by a variety of intestinal diseases, malnutrition, and drugs that injure the mucosa of the small intestine. For example, brush border enzymes are rapidly lost in normal individuals with severe diarrhea, causing a temporary, acquired enzyme deficiency. Therefore, patients suffering or recovering from such a disorder cannot drink or eat significant amounts of dairy products or sucrose without exacerbating the diarrhea. 2.
Biochemistry_Lippincott_300	Biochemistry_Lippinco	Lactose intolerance: Over 60% of the world’s adults are lactose intolerant (Fig. 7.11). This is particularly manifested in certain populations. For example, up to 90% of adults of African or Asian descent are lactase deficient. Consequently, they are less able to metabolize lactose than are individuals of Northern European origin. The age-dependent loss of lactase activity starting at approximately age 2 years represents a reduction in the amount of enzyme produced. It is thought to be caused by small variations in the DNA sequence of a region on chromosome 2 that controls expression of the gene for lactase, also on chromosome 2. Treatment for this disorder is to reduce consumption of milk; eat yogurts and some cheeses (bacterial action and aging process decrease lactose content) as well as green vegetables, such as broccoli, to ensure adequate calcium intake; use lactase-treated products; or take lactase in pill form prior to eating. [Note: Because the loss of lactase is the norm for	Biochemistry_Lippinco. Lactose intolerance: Over 60% of the world’s adults are lactose intolerant (Fig. 7.11). This is particularly manifested in certain populations. For example, up to 90% of adults of African or Asian descent are lactase deficient. Consequently, they are less able to metabolize lactose than are individuals of Northern European origin. The age-dependent loss of lactase activity starting at approximately age 2 years represents a reduction in the amount of enzyme produced. It is thought to be caused by small variations in the DNA sequence of a region on chromosome 2 that controls expression of the gene for lactase, also on chromosome 2. Treatment for this disorder is to reduce consumption of milk; eat yogurts and some cheeses (bacterial action and aging process decrease lactose content) as well as green vegetables, such as broccoli, to ensure adequate calcium intake; use lactase-treated products; or take lactase in pill form prior to eating. [Note: Because the loss of lactase is the norm for
Biochemistry_Lippincott_301	Biochemistry_Lippinco	green vegetables, such as broccoli, to ensure adequate calcium intake; use lactase-treated products; or take lactase in pill form prior to eating. [Note: Because the loss of lactase is the norm for most of the world’s adults, use of the terms adult-type hypolactasia or lactase nonpersistence rather than lactose intolerance is becoming more common.] Rare cases of congenital lactase deficiency are known.	Biochemistry_Lippinco. green vegetables, such as broccoli, to ensure adequate calcium intake; use lactase-treated products; or take lactase in pill form prior to eating. [Note: Because the loss of lactase is the norm for most of the world’s adults, use of the terms adult-type hypolactasia or lactase nonpersistence rather than lactose intolerance is becoming more common.] Rare cases of congenital lactase deficiency are known.
Biochemistry_Lippincott_302	Biochemistry_Lippinco	3. Congenital sucrase-isomaltase deficiency: This autosomal-recessive disorder results in an intolerance of ingested sucrose. Congenital SI deficiency has a prevalence of 1:5,000 in individuals of European descent and appears to be much more common (up to 1:20) in the Inuit people of Greenland and Canada. Treatment includes the dietary restriction of sucrose and enzyme replacement therapy. 4. Diagnosis: Identification of a specific enzyme deficiency can be obtained by performing oral tolerance tests with the individual disaccharides. Measurement of H2 in the breath is a reliable test for determining the amount of ingested carbohydrate not absorbed by the body, but which is metabolized instead by the intestinal flora (see Fig. 7.11). IV. CHAPTER SUMMARY	Biochemistry_Lippinco. 3. Congenital sucrase-isomaltase deficiency: This autosomal-recessive disorder results in an intolerance of ingested sucrose. Congenital SI deficiency has a prevalence of 1:5,000 in individuals of European descent and appears to be much more common (up to 1:20) in the Inuit people of Greenland and Canada. Treatment includes the dietary restriction of sucrose and enzyme replacement therapy. 4. Diagnosis: Identification of a specific enzyme deficiency can be obtained by performing oral tolerance tests with the individual disaccharides. Measurement of H2 in the breath is a reliable test for determining the amount of ingested carbohydrate not absorbed by the body, but which is metabolized instead by the intestinal flora (see Fig. 7.11). IV. CHAPTER SUMMARY
Biochemistry_Lippincott_303	Biochemistry_Lippinco	IV. CHAPTER SUMMARY Monosaccharides (Fig. 7.12) containing an aldehyde group are called aldoses, and those with a keto group are called ketoses. Disaccharides, oligosaccharides, and polysaccharides consist of monosaccharides linked by glycosidic bonds. Compounds with the same chemical formula but different structures are called isomers. Two monosaccharide isomers differing in configuration around one specific carbon atom (not the carbonyl carbon) are defined as epimers. In enantiomers (mirror images), the members of the sugar pair are designated as D-and L-isomers. When the aldehyde group on an acyclic sugar gets oxidized as a chromogenic agent gets reduced, that sugar is a reducing sugar. When a sugar cyclizes, an anomeric carbon is created from the carbonyl carbon of the aldehyde or keto group. The sugar can have two configurations, forming α or β anomers. A sugar can have its anomeric carbon linked to an –NH2 or an –	Biochemistry_Lippinco. IV. CHAPTER SUMMARY Monosaccharides (Fig. 7.12) containing an aldehyde group are called aldoses, and those with a keto group are called ketoses. Disaccharides, oligosaccharides, and polysaccharides consist of monosaccharides linked by glycosidic bonds. Compounds with the same chemical formula but different structures are called isomers. Two monosaccharide isomers differing in configuration around one specific carbon atom (not the carbonyl carbon) are defined as epimers. In enantiomers (mirror images), the members of the sugar pair are designated as D-and L-isomers. When the aldehyde group on an acyclic sugar gets oxidized as a chromogenic agent gets reduced, that sugar is a reducing sugar. When a sugar cyclizes, an anomeric carbon is created from the carbonyl carbon of the aldehyde or keto group. The sugar can have two configurations, forming α or β anomers. A sugar can have its anomeric carbon linked to an –NH2 or an –
Biochemistry_Lippincott_304	Biochemistry_Lippinco	OH group on another structure through N-and O-glycosidic bonds, respectively. Salivary α-amylase initiates digestion of dietary polysaccharides (for example, starch or glycogen), producing oligosaccharides. Pancreatic α-amylase continues the process. The final digestive processes occur at the mucosal lining of the small intestine. Several disaccharidases (for example, lactase [β-galactosidase], sucrase, isomaltase, and maltase) produce monosaccharides (glucose, galactose, and fructose). These enzymes are transmembrane proteins of the luminal brush border of intestinal mucosal cells (enterocytes). Absorption of the monosaccharides requires specific transporters. If carbohydrate degradation is deficient (as a result of heredity, disease, or drugs that injure the intestinal mucosa), undigested carbohydrate will pass into the large intestine, where it can cause osmotic diarrhea. Bacterial fermentation of the material produces large volumes of carbon dioxide and hydrogen gas, causing	Biochemistry_Lippinco. OH group on another structure through N-and O-glycosidic bonds, respectively. Salivary α-amylase initiates digestion of dietary polysaccharides (for example, starch or glycogen), producing oligosaccharides. Pancreatic α-amylase continues the process. The final digestive processes occur at the mucosal lining of the small intestine. Several disaccharidases (for example, lactase [β-galactosidase], sucrase, isomaltase, and maltase) produce monosaccharides (glucose, galactose, and fructose). These enzymes are transmembrane proteins of the luminal brush border of intestinal mucosal cells (enterocytes). Absorption of the monosaccharides requires specific transporters. If carbohydrate degradation is deficient (as a result of heredity, disease, or drugs that injure the intestinal mucosa), undigested carbohydrate will pass into the large intestine, where it can cause osmotic diarrhea. Bacterial fermentation of the material produces large volumes of carbon dioxide and hydrogen gas, causing
Biochemistry_Lippincott_305	Biochemistry_Lippinco	carbohydrate will pass into the large intestine, where it can cause osmotic diarrhea. Bacterial fermentation of the material produces large volumes of carbon dioxide and hydrogen gas, causing abdominal cramps, diarrhea, and flatulence. Lactose intolerance, primarily caused by the age-dependent loss of lactase (adult-type hypolactasia), is by far the most common of these deficiencies.	Biochemistry_Lippinco. carbohydrate will pass into the large intestine, where it can cause osmotic diarrhea. Bacterial fermentation of the material produces large volumes of carbon dioxide and hydrogen gas, causing abdominal cramps, diarrhea, and flatulence. Lactose intolerance, primarily caused by the age-dependent loss of lactase (adult-type hypolactasia), is by far the most common of these deficiencies.
Biochemistry_Lippincott_306	Biochemistry_Lippinco	Choose the ONE best answer. .1. Which of the following statements best describes glucose? A. It is a C-4 epimer of galactose. B. It is a ketose and usually exists as a furanose ring in solution. C. It is produced from dietary starch by the action of α-amylase. D. It is utilized in biological systems only in the L-isomeric form. Correct answer = A. Because glucose and galactose differ only in configuration around carbon 4, they are C-4 epimers that are interconvertible by the action of an epimerase. Glucose is an aldose sugar that typically exists as a pyranose ring in solution. Fructose, however, is a ketose with a furanose ring. α-Amylase does not produce monosaccharides. The D-isomeric form of carbohydrates is the form typically found in biologic systems, in contrast to amino acids that typically are found in the L-isomeric form.	Biochemistry_Lippinco. Choose the ONE best answer. .1. Which of the following statements best describes glucose? A. It is a C-4 epimer of galactose. B. It is a ketose and usually exists as a furanose ring in solution. C. It is produced from dietary starch by the action of α-amylase. D. It is utilized in biological systems only in the L-isomeric form. Correct answer = A. Because glucose and galactose differ only in configuration around carbon 4, they are C-4 epimers that are interconvertible by the action of an epimerase. Glucose is an aldose sugar that typically exists as a pyranose ring in solution. Fructose, however, is a ketose with a furanose ring. α-Amylase does not produce monosaccharides. The D-isomeric form of carbohydrates is the form typically found in biologic systems, in contrast to amino acids that typically are found in the L-isomeric form.
Biochemistry_Lippincott_307	Biochemistry_Lippinco	.2. A young man entered his physician’s office complaining of bloating and diarrhea. His eyes were sunken, and the physician noted additional signs of dehydration. The patient’s temperature was normal. He explained that the episode had occurred following a birthday party at which he had participated in an ice cream–eating contest. The patient reported prior episodes of a similar nature following ingestion of a significant amount of dairy products. This clinical picture is most probably due to a deficiency in the activity of: A. isomaltase. B. lactase. C. pancreatic α-amylase. D. salivary α-amylase. E. sucrase. Correct answer = B. The physical symptoms suggest a deficiency in an enzyme responsible for carbohydrate degradation. The symptoms observed following the ingestion of dairy products suggest that the patient is deficient in lactase as a result of the age-dependent reduction in expression of the enzyme.	Biochemistry_Lippinco. .2. A young man entered his physician’s office complaining of bloating and diarrhea. His eyes were sunken, and the physician noted additional signs of dehydration. The patient’s temperature was normal. He explained that the episode had occurred following a birthday party at which he had participated in an ice cream–eating contest. The patient reported prior episodes of a similar nature following ingestion of a significant amount of dairy products. This clinical picture is most probably due to a deficiency in the activity of: A. isomaltase. B. lactase. C. pancreatic α-amylase. D. salivary α-amylase. E. sucrase. Correct answer = B. The physical symptoms suggest a deficiency in an enzyme responsible for carbohydrate degradation. The symptoms observed following the ingestion of dairy products suggest that the patient is deficient in lactase as a result of the age-dependent reduction in expression of the enzyme.
Biochemistry_Lippincott_308	Biochemistry_Lippinco	.3. Routine examination of the urine of an asymptomatic pediatric patient showed a positive reaction with Clinitest (a copper reduction method of detecting reducing sugars) but a negative reaction with the glucose oxidase test for detecting glucose. Using these data, show on the chart below which of the sugars could (YES) or could not (NO) be present in the urine of this individual. Each of the listed sugars, except for sucrose and glucose, could be present in the urine of this individual. Clinitest is a nonspecific test that produces a change in color if urine is positive for reducing substances such as reducing sugars (fructose, galactose, glucose, lactose, xylulose). Because sucrose is not a reducing sugar, it is not detected by Clinitest. The glucose oxidase test will detect only glucose, and it cannot detect other sugars. The negative glucose oxidase test coupled with a positive reducing sugar test means that glucose cannot be the reducing sugar in the patient’s urine.	Biochemistry_Lippinco. .3. Routine examination of the urine of an asymptomatic pediatric patient showed a positive reaction with Clinitest (a copper reduction method of detecting reducing sugars) but a negative reaction with the glucose oxidase test for detecting glucose. Using these data, show on the chart below which of the sugars could (YES) or could not (NO) be present in the urine of this individual. Each of the listed sugars, except for sucrose and glucose, could be present in the urine of this individual. Clinitest is a nonspecific test that produces a change in color if urine is positive for reducing substances such as reducing sugars (fructose, galactose, glucose, lactose, xylulose). Because sucrose is not a reducing sugar, it is not detected by Clinitest. The glucose oxidase test will detect only glucose, and it cannot detect other sugars. The negative glucose oxidase test coupled with a positive reducing sugar test means that glucose cannot be the reducing sugar in the patient’s urine.
Biochemistry_Lippincott_309	Biochemistry_Lippinco	.4. Why are α-glucosidase inhibitors that are taken with meals, such as acarbose and miglitol, used in the treatment of diabetes? What effect should these drugs have on the digestion of lactose? α-Glucosidase inhibitors slow the production of glucose from dietary carbohydrates, thereby reducing the postprandial rise in blood glucose and facilitating better blood glucose control in diabetic patients. These drugs have no effect on lactose digestion because the disaccharide lactose contains a βglycosidic bond, not an α-glycosidic bond. Introduction to Metabolism and Glycolysis 8 For additional ancillary materials related to this chapter, please visit thePoint. I. METABOLISM OVERVIEW	Biochemistry_Lippinco. .4. Why are α-glucosidase inhibitors that are taken with meals, such as acarbose and miglitol, used in the treatment of diabetes? What effect should these drugs have on the digestion of lactose? α-Glucosidase inhibitors slow the production of glucose from dietary carbohydrates, thereby reducing the postprandial rise in blood glucose and facilitating better blood glucose control in diabetic patients. These drugs have no effect on lactose digestion because the disaccharide lactose contains a βglycosidic bond, not an α-glycosidic bond. Introduction to Metabolism and Glycolysis 8 For additional ancillary materials related to this chapter, please visit thePoint. I. METABOLISM OVERVIEW
Biochemistry_Lippincott_310	Biochemistry_Lippinco	In Chapter 5, individual enzymic reactions were analyzed in an effort to explain the mechanisms of catalysis. However, in cells, these reactions rarely occur in isolation. Instead, they are organized into multistep sequences called pathways, such as that of glycolysis (Fig. 8.1). In a pathway, the product of one reaction serves as the substrate of the subsequent reaction. Most pathways can be classified as either catabolic (degradative) or anabolic (synthetic). Catabolic pathways break down complex molecules, such as proteins, polysaccharides, and lipids, to a few simple molecules (for example, carbon dioxide, ammonia, and water). Anabolic pathways form complex end products from simple precursors, for example, the synthesis of the polysaccharide glycogen from glucose. [Note: Pathways that regenerate a component are called cycles.] Different pathways can intersect, forming an integrated and purposeful network of chemical reactions. Metabolism is the sum of all the chemical changes	Biochemistry_Lippinco. In Chapter 5, individual enzymic reactions were analyzed in an effort to explain the mechanisms of catalysis. However, in cells, these reactions rarely occur in isolation. Instead, they are organized into multistep sequences called pathways, such as that of glycolysis (Fig. 8.1). In a pathway, the product of one reaction serves as the substrate of the subsequent reaction. Most pathways can be classified as either catabolic (degradative) or anabolic (synthetic). Catabolic pathways break down complex molecules, such as proteins, polysaccharides, and lipids, to a few simple molecules (for example, carbon dioxide, ammonia, and water). Anabolic pathways form complex end products from simple precursors, for example, the synthesis of the polysaccharide glycogen from glucose. [Note: Pathways that regenerate a component are called cycles.] Different pathways can intersect, forming an integrated and purposeful network of chemical reactions. Metabolism is the sum of all the chemical changes
Biochemistry_Lippincott_311	Biochemistry_Lippinco	that regenerate a component are called cycles.] Different pathways can intersect, forming an integrated and purposeful network of chemical reactions. Metabolism is the sum of all the chemical changes occurring in a cell, a tissue, or the body. The next several chapters focus on the central metabolic pathways that are involved in synthesizing and degrading carbohydrates, lipids, and amino acids.	Biochemistry_Lippinco. that regenerate a component are called cycles.] Different pathways can intersect, forming an integrated and purposeful network of chemical reactions. Metabolism is the sum of all the chemical changes occurring in a cell, a tissue, or the body. The next several chapters focus on the central metabolic pathways that are involved in synthesizing and degrading carbohydrates, lipids, and amino acids.
Biochemistry_Lippincott_312	Biochemistry_Lippinco	A. Metabolic map Metabolism is best understood by examining its component pathways. Each pathway is composed of multienzyme sequences, and each enzyme, in turn, may exhibit important catalytic or regulatory features. A metabolic map containing the important central pathways of energy metabolism is presented in Figure 8.2. This “big picture” view of metabolism is useful in tracing connections between pathways, visualizing the purposeful movement of metabolic intermediates (metabolites), and depicting the effect on the flow of intermediates if a pathway is blocked (for example, by a drug or an inherited deficiency of an enzyme). [Note: The metabolome is the full complement of metabolites in an organism.] Throughout the next three units of this book, each pathway under discussion will be repeatedly featured as part of the major metabolic map shown in Figure 8.2. intermediates of protein metabolism. UDP = uridine diphosphate; P = phosphate; -	Biochemistry_Lippinco. A. Metabolic map Metabolism is best understood by examining its component pathways. Each pathway is composed of multienzyme sequences, and each enzyme, in turn, may exhibit important catalytic or regulatory features. A metabolic map containing the important central pathways of energy metabolism is presented in Figure 8.2. This “big picture” view of metabolism is useful in tracing connections between pathways, visualizing the purposeful movement of metabolic intermediates (metabolites), and depicting the effect on the flow of intermediates if a pathway is blocked (for example, by a drug or an inherited deficiency of an enzyme). [Note: The metabolome is the full complement of metabolites in an organism.] Throughout the next three units of this book, each pathway under discussion will be repeatedly featured as part of the major metabolic map shown in Figure 8.2. intermediates of protein metabolism. UDP = uridine diphosphate; P = phosphate; -
Biochemistry_Lippincott_313	Biochemistry_Lippinco	intermediates of protein metabolism. UDP = uridine diphosphate; P = phosphate; - CoA = coenzyme A; CO2 = carbon dioxide; HCO3 = bicarbonate; NH3 = ammonia. B. Catabolic pathways Catabolic reactions serve to capture chemical energy in the form of ATP from the degradation of energy-rich fuel molecules. ATP generation by degradation of complex molecules occurs in three stages, as shown in Figure 8.3. [Note: Catabolic pathways are typically oxidative and require oxidized coenzymes such as nicotinamide adenine dinucleotide (NAD+).] Catabolism also allows molecules in the diet (or nutrient molecules stored in cells) to be converted into basic building blocks needed for the synthesis of complex molecules. Catabolism, then, is a convergent process (that is, a wide variety of molecules are transformed into a few common end products). 1.	Biochemistry_Lippinco. intermediates of protein metabolism. UDP = uridine diphosphate; P = phosphate; - CoA = coenzyme A; CO2 = carbon dioxide; HCO3 = bicarbonate; NH3 = ammonia. B. Catabolic pathways Catabolic reactions serve to capture chemical energy in the form of ATP from the degradation of energy-rich fuel molecules. ATP generation by degradation of complex molecules occurs in three stages, as shown in Figure 8.3. [Note: Catabolic pathways are typically oxidative and require oxidized coenzymes such as nicotinamide adenine dinucleotide (NAD+).] Catabolism also allows molecules in the diet (or nutrient molecules stored in cells) to be converted into basic building blocks needed for the synthesis of complex molecules. Catabolism, then, is a convergent process (that is, a wide variety of molecules are transformed into a few common end products). 1.
Biochemistry_Lippincott_314	Biochemistry_Lippinco	1. Hydrolysis of complex molecules: In the first stage, complex molecules are broken down into their component building blocks. For example, proteins are degraded to amino acids, polysaccharides to monosaccharides, and fats (triacylglycerols) to free fatty acids and glycerol. 2. Conversion of building blocks to simple intermediates: In the second stage, these diverse building blocks are further degraded to acetyl coenzyme A (CoA) and a few other simple molecules. Some energy is captured as ATP, but the amount is small compared with the energy produced during the third stage of catabolism. 3. Oxidation of acetyl coenzyme A: The tricarboxylic acid (TCA) cycle (see p. 109) is the final common pathway in the oxidation of fuel molecules that produce acetyl CoA. Oxidation of acetyl CoA generates large amounts of ATP via oxidative phosphorylation as electrons flow from NADH and flavin adenine dinucleotide (FADH2) to oxygen ([O2] see p. 73). C. Anabolic pathways	Biochemistry_Lippinco. 1. Hydrolysis of complex molecules: In the first stage, complex molecules are broken down into their component building blocks. For example, proteins are degraded to amino acids, polysaccharides to monosaccharides, and fats (triacylglycerols) to free fatty acids and glycerol. 2. Conversion of building blocks to simple intermediates: In the second stage, these diverse building blocks are further degraded to acetyl coenzyme A (CoA) and a few other simple molecules. Some energy is captured as ATP, but the amount is small compared with the energy produced during the third stage of catabolism. 3. Oxidation of acetyl coenzyme A: The tricarboxylic acid (TCA) cycle (see p. 109) is the final common pathway in the oxidation of fuel molecules that produce acetyl CoA. Oxidation of acetyl CoA generates large amounts of ATP via oxidative phosphorylation as electrons flow from NADH and flavin adenine dinucleotide (FADH2) to oxygen ([O2] see p. 73). C. Anabolic pathways
Biochemistry_Lippincott_315	Biochemistry_Lippinco	73). C. Anabolic pathways In contrast to catabolism, anabolism is a divergent process in which a few biosynthetic precursors (such as amino acids) form a wide variety of polymeric, or complex, products (such as proteins [Fig. 8.4]). Anabolic reactions require energy (are endergonic), which is generally provided by the hydrolysis of ATP to adenosine diphosphate (ADP) and inorganic phosphate (Pi). [Note: Catabolic reactions generate energy (are exergonic).] Anabolic reactions often involve chemical reductions in which the reducing power is most frequently provided by the electron donor NADPH (phosphorylated NADH, see p. 147). II. METABOLISM REGULATION	Biochemistry_Lippinco. 73). C. Anabolic pathways In contrast to catabolism, anabolism is a divergent process in which a few biosynthetic precursors (such as amino acids) form a wide variety of polymeric, or complex, products (such as proteins [Fig. 8.4]). Anabolic reactions require energy (are endergonic), which is generally provided by the hydrolysis of ATP to adenosine diphosphate (ADP) and inorganic phosphate (Pi). [Note: Catabolic reactions generate energy (are exergonic).] Anabolic reactions often involve chemical reductions in which the reducing power is most frequently provided by the electron donor NADPH (phosphorylated NADH, see p. 147). II. METABOLISM REGULATION
Biochemistry_Lippincott_316	Biochemistry_Lippinco	Anabolic reactions often involve chemical reductions in which the reducing power is most frequently provided by the electron donor NADPH (phosphorylated NADH, see p. 147). II. METABOLISM REGULATION The pathways of metabolism must be coordinated so that the production of energy or the synthesis of end products meets the needs of the cell. Furthermore, individual cells function as part of a community of interacting tissues, not in isolation. Thus, a sophisticated communication system has evolved to coordinate the functions of the body. Regulatory signals that inform an individual cell of the metabolic state of the body as a whole include hormones, neurotransmitters, and the availability of nutrients. These, in turn, influence signals generated within the cell (Fig. 8.5). A. Intracellular communication	Biochemistry_Lippinco. Anabolic reactions often involve chemical reductions in which the reducing power is most frequently provided by the electron donor NADPH (phosphorylated NADH, see p. 147). II. METABOLISM REGULATION The pathways of metabolism must be coordinated so that the production of energy or the synthesis of end products meets the needs of the cell. Furthermore, individual cells function as part of a community of interacting tissues, not in isolation. Thus, a sophisticated communication system has evolved to coordinate the functions of the body. Regulatory signals that inform an individual cell of the metabolic state of the body as a whole include hormones, neurotransmitters, and the availability of nutrients. These, in turn, influence signals generated within the cell (Fig. 8.5). A. Intracellular communication
Biochemistry_Lippincott_317	Biochemistry_Lippinco	A. Intracellular communication The rate of a metabolic pathway can respond to regulatory signals that arise from within the cell. For example, the rate may be influenced by the availability of substrates, product inhibition, or alterations in the levels of allosteric activators or inhibitors. These intracellular signals typically elicit rapid responses and are important for the moment-to-moment regulation of metabolism. B. Intercellular communication	Biochemistry_Lippinco. A. Intracellular communication The rate of a metabolic pathway can respond to regulatory signals that arise from within the cell. For example, the rate may be influenced by the availability of substrates, product inhibition, or alterations in the levels of allosteric activators or inhibitors. These intracellular signals typically elicit rapid responses and are important for the moment-to-moment regulation of metabolism. B. Intercellular communication
Biochemistry_Lippincott_318	Biochemistry_Lippinco	B. Intercellular communication The ability to respond to intercellular signals is essential for the development and survival of organisms. Signaling between cells provides for long-range integration of metabolism and usually results in a response, such as a change in gene expression, that is slower than is seen with intracellular signals. Communication between cells can be mediated, for example, by surface-to-surface contact and, in some tissues, by formation of gap junctions, allowing direct communication between the cytoplasms of adjacent cells. However, for energy metabolism, the most important route of communication is chemical signaling between cells by blood-borne hormones or by neurotransmitters. C. Second messenger systems	Biochemistry_Lippinco. B. Intercellular communication The ability to respond to intercellular signals is essential for the development and survival of organisms. Signaling between cells provides for long-range integration of metabolism and usually results in a response, such as a change in gene expression, that is slower than is seen with intracellular signals. Communication between cells can be mediated, for example, by surface-to-surface contact and, in some tissues, by formation of gap junctions, allowing direct communication between the cytoplasms of adjacent cells. However, for energy metabolism, the most important route of communication is chemical signaling between cells by blood-borne hormones or by neurotransmitters. C. Second messenger systems
Biochemistry_Lippincott_319	Biochemistry_Lippinco	Hormones and neurotransmitters can be thought of as signals and their receptors as signal detectors. Receptors respond to a bound ligand by initiating a series of reactions that ultimately result in specific intracellular responses. Second messenger molecules, so named because they intervene between the original extracellular messenger (the neurotransmitter or hormone) and the ultimate intracellular effect, are part of the cascade of events that converts (transduces) ligand binding into a response. Two of the most widely recognized second messenger systems are the calcium/phosphatidylinositol system (see p. 205) and the adenylyl cyclase (adenylate cyclase) system, which is particularly important in regulating the pathways of intermediary metabolism. Both involve the binding of ligands, such as epinephrine or glucagon, to specific G protein–coupled receptors (GPCR) on the cell (plasma) membrane. GPCR are characterized by an extracellular ligand-binding domain, seven transmembrane α	Biochemistry_Lippinco. Hormones and neurotransmitters can be thought of as signals and their receptors as signal detectors. Receptors respond to a bound ligand by initiating a series of reactions that ultimately result in specific intracellular responses. Second messenger molecules, so named because they intervene between the original extracellular messenger (the neurotransmitter or hormone) and the ultimate intracellular effect, are part of the cascade of events that converts (transduces) ligand binding into a response. Two of the most widely recognized second messenger systems are the calcium/phosphatidylinositol system (see p. 205) and the adenylyl cyclase (adenylate cyclase) system, which is particularly important in regulating the pathways of intermediary metabolism. Both involve the binding of ligands, such as epinephrine or glucagon, to specific G protein–coupled receptors (GPCR) on the cell (plasma) membrane. GPCR are characterized by an extracellular ligand-binding domain, seven transmembrane α
Biochemistry_Lippincott_320	Biochemistry_Lippinco	such as epinephrine or glucagon, to specific G protein–coupled receptors (GPCR) on the cell (plasma) membrane. GPCR are characterized by an extracellular ligand-binding domain, seven transmembrane α helices, and an intracellular domain that interacts with trimeric G proteins (Fig. 8.6). [Note: Insulin, another key regulator of metabolism, binds a membrane tyrosine kinase receptor (see p. 311) and not a GPCR.]	Biochemistry_Lippinco. such as epinephrine or glucagon, to specific G protein–coupled receptors (GPCR) on the cell (plasma) membrane. GPCR are characterized by an extracellular ligand-binding domain, seven transmembrane α helices, and an intracellular domain that interacts with trimeric G proteins (Fig. 8.6). [Note: Insulin, another key regulator of metabolism, binds a membrane tyrosine kinase receptor (see p. 311) and not a GPCR.]
Biochemistry_Lippincott_321	Biochemistry_Lippinco	D. Adenylyl cyclase The recognition of a chemical signal by some GPCR, such as the β-and α2adrenergic receptors, triggers either an increase or a decrease in the activity of adenylyl cyclase (AC). This is a membrane-bound enzyme that converts ATP to 3ʹ,5ʹ-adenosine monophosphate (cyclic AMP, or cAMP). The chemical signals are most often hormones or neurotransmitters, each of which binds to a unique type of GPCR. Therefore, tissues that respond to more than one signal must have several different GPCR, each of which can be linked to AC.	Biochemistry_Lippinco. D. Adenylyl cyclase The recognition of a chemical signal by some GPCR, such as the β-and α2adrenergic receptors, triggers either an increase or a decrease in the activity of adenylyl cyclase (AC). This is a membrane-bound enzyme that converts ATP to 3ʹ,5ʹ-adenosine monophosphate (cyclic AMP, or cAMP). The chemical signals are most often hormones or neurotransmitters, each of which binds to a unique type of GPCR. Therefore, tissues that respond to more than one signal must have several different GPCR, each of which can be linked to AC.
Biochemistry_Lippincott_322	Biochemistry_Lippinco	1. Guanosine triphosphate–dependent regulatory proteins: The effect of the activated, occupied GPCR on second messenger formation is indirect, mediated by specialized trimeric proteins (α, β, and γ subunits) of the cell membrane. These proteins, referred to as G proteins because the α subunit binds guanosine di-or triphosphates (GDP or GTP), form a link in the chain of communication between the receptor and AC. In the inactive form of a G protein, the α subunit is bound to GDP (Fig. 8.7). Ligand binding causes a conformational change in the receptor, triggering replacement of this GDP with GTP. The GTP-bound form of the α subunit dissociates from the βγ subunits and moves to AC, affecting enzyme activity. Many molecules of active Gα protein are formed by one activated receptor. [Note: The ability of a hormone or neurotransmitter to stimulate or inhibit AC depends on the type of Gα protein that is linked to the receptor. One type, designated Gs, stimulates AC (see Fig. 8.7), whereas	Biochemistry_Lippinco. 1. Guanosine triphosphate–dependent regulatory proteins: The effect of the activated, occupied GPCR on second messenger formation is indirect, mediated by specialized trimeric proteins (α, β, and γ subunits) of the cell membrane. These proteins, referred to as G proteins because the α subunit binds guanosine di-or triphosphates (GDP or GTP), form a link in the chain of communication between the receptor and AC. In the inactive form of a G protein, the α subunit is bound to GDP (Fig. 8.7). Ligand binding causes a conformational change in the receptor, triggering replacement of this GDP with GTP. The GTP-bound form of the α subunit dissociates from the βγ subunits and moves to AC, affecting enzyme activity. Many molecules of active Gα protein are formed by one activated receptor. [Note: The ability of a hormone or neurotransmitter to stimulate or inhibit AC depends on the type of Gα protein that is linked to the receptor. One type, designated Gs, stimulates AC (see Fig. 8.7), whereas