CHAPTER 38: CARBOHYDRATE DIGESTION
Chapter 38: Carbohydrate Digestion
Monosaccharides (largely hexoses and pentoses) require no intestinal digestion prior to absorption; however, oligosaccharides must be hydrolyzed to monosaccharides before they can be absorbed. Since mammals lack the enzyme cellulase, they are incapable of carrying out the constitutive digestion of cellulose (which contains b-1,4 glycosidic linkages). However, they can digest (i.e., hydrolyze) dietary starch and glycogen (which contain a-1,4 and a-1,6 glycosidic linkages). Sites for starch and glycogen digestion are in the mouth and upper small intestine. Most monosaccharide absorption occurs in the duodenum and jejunum.
Salivary a-Amylase (Ptyalin): With the exception of ruminants and carnivores (who do not secrete salivary a-amylase), this endo-glycosidase (or endo-glucosidase) initiates hydrolysis of a-1,4 glycosidic bonds within dietary glucose polymers, (e.g., glycogen and starch), but it will not attack a-1,6 or terminal a-1,4 glycosidic linkages. Glycogen is a product of animal metabolism, whereas starch is the comparable plant storage form of glucose. Glucose molecules in glycogen are mostly in long chains held together by a-1,4 glycosidic bonds, but there is some chain-branching produced by a-1,6-linkages. Amylopectin, which constitutes 80-85% of dietary starch, is similar but less branched, whereas amylose, the other component of starch, is a straight chain glucose polymer containing only a-1,4 linkages.
Oligosaccharides are products of salivary a-amylase digestion. The major oligosaccharides are dextrins (with a-limit dextrins being the first formed products), compounds with an average chain length of 8-10 glucose residues containing the a-1,6 branches. Small amounts of maltose (an a-1,4 disaccharide), and maltotriose (an a-1,4 trisaccharide) are also formed at this point. The optimal pH for salivary a-amylase is 6.7, and its action is inhibited by acidic gastric juice when food enters the stomach. Therefore, little starch and glycogen digestion occurs during the short time food is in the mouth, and even less will occur in the stomach unless it fails to mix its contents fully.
Intestinal Carbohydrate Digestion: There are two phases of intestinal carbohydrate digestion. The first occurs in the lumen of the small intestine, and is commonly referred to as the hormonal or pancreatic phase. The second occurs in brush border membranes, and involves the action of a number of integral membrane proteins with saccharidase activity. Unlike salivary and pancreatic a-amylase, most of the surface oligosaccharidases are exoenzymes which clip off one monosaccharide at a time.
Luminal Phase (Pancreatic a-Amylase): The entry of partially digested acidic chyme into the duodenum stimulates specialized mucosal cells to release two important polypeptide hormones into blood; secretin (from duodenal S cells), and cholecystokinin (CCK, from duodenal I cells). These hormones then stimulate exocrine pancreatic secretions into the duodenal lumen containing NaHCO3 (needed to neutralize acidic chyme), and digestive enzymes (including a-amylase). Both salivary and pancreatic a-amylase (which are similar enzymes), continue internal starch, glycogen, and dextrin digestion in a favorable neutral duodenal pH environment (i.e., pH. 7). Polysaccharides are digested to a mixture of dextrins and isomaltose (which contain all of the a-1,6 branch-point linkages), as well as maltose and maltotriose. Most salivary and pancreatic a-amylase is destroyed by trypsin activity in lower portions of the intestinal tract, although some amylase activity may be present in feces.
Brush Border Phase (Oligosaccharidases): Enzymes responsible for the final phase of carbohydrate digestion are located in brush border membranes of the small intestine, and have their active sites extending into the lumen. They are generally protected from degradation by a glycocalix mucus coat. However, since they are anaerobic enzymes, like all digestive enzymes, when they are cleaved from the brush border, or mucosal cells are sloughed into the lumen, these enzymes remain active. Some of these brush border enzymes have more than one substrate. Isomaltase (also called a-dextrinase or a-1,6-glucosidase), is mainly responsible for hydrolysis of a-1,6- glycosidic linkages in isomaltose and the dextrins. However, along with maltase (also called a-glucosidase) and sucrase (also called invertase), it also breaks down maltotriose and maltose. Sucrase/isomaltase is a bifunctional enzyme, having one domain with isomaltase activity, and another with sucrase activity on the same polypeptide. Sucrase and isomaltase are reportedly synthesized as a single polypeptide chain and inserted into the brush border membrane. This protein is then hydrolyzed by pancreatic proteases into sucrase and isomaltase subunits, but the subunits reassociate noncovalently at the intestinal surface.
Dietary disaccharides (sucrose, lactose, and trehalose) are digested by their appropriate disaccharidases. Trehalose is a rare disaccharide found in young mushrooms, and lactose, which is found in milk, generally disappears from the animal diet following weaning.
A brush border galactocerebrosidase (bgalactosidase or lactase) catalyzes digestion of dietary galactocerebrosides (galactosylceramides), as well as lactose (a glucose-galactose disaccharide). Although lactase is a labile enzyme, maltase and sucrase are more adaptive, and therefore inducible by their substrates.
A glucocerebrosidase (b-glucosidase) is also present in the brush border of the small intestine, which catalyzes digestion of dietary glucocerebrosides. Additionally, another member of the a-amylase family (i.e., enzymes found in a number of organs and tissues in addition to the pancreas and salivary glands (e.g., semen, testes, ovaries, fallopian tubes, striated muscle, lung, and adipose tissue), is present in the brush border of the small intestine. This enzyme, glucoamylase or exo a-1,4-glucosidase, catalyzes hydrolysis of terminal a-1,4-glycosidic bonds in starch, glycogen, and the dextrins.
In pancreatic insufficiency, as well in a variety of bacterial and enteric infections, transient loss of carbohydrate digestive activity can occur. As a result, increased amounts of di-, oligo-, and polysaccharides that are not hydrolyzed by a-amylase and/or intestinal brush border oligosaccharidases, cannot be absorbed: therefore, they reach the distal portion the intestine, which contains bacteria from the lower ileum on down. Bacteria can effectively metabolize carbohydrate polymers because they possess many more types of saccharidases than do mammals. Products of anaerobic bacterial carbohydrate digestion include short-chain volatile fatty acids, lactate, hydrogen gas (H2), methane (CH4), and carbon dioxide (CO2). These compounds, if not absorbed, can cause fluid secretion, increased intestinal motility, and cramps (i.e., diarrhea), either because of increased intraluminal osmotic pressure, distension of the gut, or because of a direct irritant effect of bacterial degradation products on the intestinal mucosa. Some leguminous seeds (e.g., beans, peas, soya) can also be difficult for some animals to digest since they contain a modified sucrose to which one or more galactose moieties are linked. The glycosidic bonds of galactose are in the a-configuration, which can only be split by bacterial enzymes. The simplest sugar of this family is raffinose (a Gal(1,6)-a Glc(1,2)-b Fru).
Intestinal Monosaccharide Absorption: Hexoses and pentoses are rapidly absorbed across the wall of the small intestine. Essentially all are removed before remains of a meal reach the terminal part of the ileum. Monosaccharides pass from mucosal cells to interstitial fluid, and then to capillary blood that drains into the hepatic portal vein. The mucosal cell process involves movement across the apical membrane on the luminal side, and the basolateral membrane on the serosal side of the cell.
Early experiments concerning absorption rates for glucose from solutions perfused through the intestines of guinea pigs, showed that the bulk of glucose absorption is oxygen dependent. Therefore, it was concluded that active transport is involved, and that only a small amount of glucose is normally absorbed via a passive, diffusional mechanism. In order to explain how the active component occurs, a carrier has been identified which binds both glucose and Na+ at separate sites, and which transports them both through the apical membrane using sodium's electrochemical gradient. Both glucose and galactose transport are uniquely affected by the amount of Na+ in the intestinal lumen because they share, with Na+, the same cotransporter, or symport, and therefore compete for uptake. This transporter, known as the sodium-dependent glucose transporter (SGLT-1), is also found in apical membranes of proximal renal tubular epithelial cells. It is insulin-independent, does not require ATP (directly), and can transport these sugars (but not Na+) against their concentration gradients.
Since the intracellular Na+ concentration is low in intestinal and proximal renal tubular epithelial cells, as it is in other cells, Na+ moves into the cell along its concentration gradient. Glucose or galactose moves with Na+ , with release occurring inside the cell. The Na+ is then actively transported into the lateral inter[1]cellular space (in a 3:2 exchange with K+), and glucose and/or galactose are transported by facilitated diffusion, using an insulin-inde[1]pendent GLUT-2 transporter, into the interstitium and thence into capillary blood. Thus, Na+ /glucose/galactose cotransport is an example of secondary active transport, with energy from ATP used to drive Na+ /K+ ATPase. Once Na+ reaches lateral intercellular spaces, it is free to diffuse down its concentration gradient, either back into the lumen or toward blood. When the apical Na+ /glucose/galactose cotransporter is congenitally defective, resulting glucose/galactose malabsorption causes severe diarrhea that can be fatal if glucose and galactose are not promptly removed from the diet.
Fructose utilizes a slightly different mechanism for intestinal absorption. The rate of fructose absorption is generally about 3 to 6 times slower than that of overall glucose absorption, and it is not apparently driven by a secondary-active mechanism. It is, however, saturable. Fructose is transported by Na+ -independent facilitated diffusion into enterocytes (along with some glucose and galactose), using the insulin-independent GLUT-5 transporter. It is transported out of enterocytes, along with glucose and galactose, using the GLUT-2 transporter. Some fructose is converted to glucose inside mucosal cells. Additionally, glucose (and fructose) can also enter into intracellular metabolism. About 10% of available glucose is thought to enter the hexose monophosphate shunt of enterocytes. Since mucosal cells have a high rate of glycolysis, the lactate so produced anaerobically diffuses into portal blood where it can be extracted and metabolized by the liver.
Intestinal pentose absorption is thought to occur by simple passive diffusion, and is not apparently associated with the SGLT or GLUT transporters. The molecular configurations that appear to be necessary for the secondary active transport of monosaccharides by the SGLT-1 transporter are the following: The OH on carbon 2 should have the same configuration as that in glucose, and an a-pyranose ring must be present. Both of these conditions are present in the hexoses glucose and galactose, but not in fructose.
SUMMARY
Chapter 38 discusses carbohydrate digestion in mammals. Monosaccharides, such as hexoses and pentoses, do not require digestion before absorption. However, oligosaccharides need to be hydrolyzed into monosaccharides before absorption. Mammals lack the enzyme cellulase, so they cannot digest cellulose. They can digest dietary starch and glycogen, which contain different glycosidic linkages. Starch and glycogen digestion occurs in the mouth and upper small intestine. Salivary a-amylase initiates the digestion of starch and glycogen. In the small intestine, there are two phases of carbohydrate digestion: the luminal phase and the brush border phase. In the luminal phase, pancreatic a-amylase continues the digestion of starch, glycogen, and dextrins. In the brush border phase, various enzymes in the brush border membranes of the small intestine break down oligosaccharides into monosaccharides. Hexoses and pentoses are rapidly absorbed in the small intestine, and their absorption is dependent on active transport. Glucose and galactose are transported using a sodium-dependent glucose transporter, while fructose is transported through facilitated diffusion. Pentose absorption occurs through passive diffusion.
OUTLINE
I. Monosaccharides
Monosaccharides (hexoses and pentoses) do not require intestinal digestion before absorption
Oligosaccharides must be hydrolyzed to monosaccharides before absorption
Mammals lack cellulase enzyme, cannot digest cellulose
Can digest dietary starch and glycogen
II. Salivary a-Amylase
Initiates hydrolysis of a-1,4 glycosidic bonds in glycogen and starch
Does not attack a-1,6 or terminal a-1,4 glycosidic linkages
Optimal pH is 6.7
Action inhibited by acidic gastric juice in the stomach
III. Intestinal Carbohydrate Digestion
Two phases: luminal phase and brush border phase
Luminal phase: pancreatic a-amylase continues digestion in duodenum
Polysaccharides digested to dextrins, isomaltose, maltose, and maltotriose
Brush border phase: exoenzymes in brush border membranes hydrolyze oligosaccharides
IV. Intestinal Monosaccharide Absorption
Hexoses and pentoses rapidly absorbed in small intestine
Active transport involved, glucose and galactose transported with Na+
Sodium-dependent glucose transporter (SGLT-1) responsible for transport
Fructose absorbed by facilitated diffusion using GLUT-5 transporter
Pentose absorption occurs by passive diffusion
V. Disorders and Malabsorption
Pancreatic insufficiency and bacterial infections can cause loss of carbohydrate digestive activity
Bacteria metabolize carbohydrates, produce compounds that can cause diarrhea
Some leguminous seeds and congenital defects can lead to malabsorption
Fructose absorption slower and different mechanism compared to glucose and galactose
QUESTIONS
Qcard 1:
Question: What is the process by which monosaccharides are absorbed in the small intestine?
Answer: Monosaccharides pass from mucosal cells to interstitial fluid, and then to capillary blood that drains into the hepatic portal vein.
Qcard 2:
Question: What is the role of salivary a-amylase in carbohydrate digestion?
Answer: Salivary a-amylase initiates hydrolysis of a-1,4 glycosidic bonds within dietary glucose polymers, such as glycogen and starch.
Qcard 3:
Question: What are the major oligosaccharides formed during salivary a-amylase digestion?
Answer: The major oligosaccharides formed are dextrins, with a-limit dextrins being the first formed products.
Qcard 4:
Question: What is the optimal pH for salivary a-amylase?
Answer: The optimal pH for salivary a-amylase is 6.7.
Qcard 5:
Question: What are the two phases of intestinal carbohydrate digestion?
Answer: The first phase occurs in the lumen of the small intestine, and the second phase occurs in brush border membranes.
Qcard 6:
Question: What is the role of pancreatic a-amylase in carbohydrate digestion?
Answer: Pancreatic a-amylase continues the digestion of starch, glycogen, and dextrins in the duodenum.
Qcard 7:
Question: What are the enzymes responsible for the final phase of carbohydrate digestion?
Answer: Enzymes located in the brush border membranes of the small intestine, such as isomaltase, maltase, and sucrase, are responsible for the final phase of carbohydrate digestion.
Qcard 8:
Question: How are hexoses and pentoses absorbed in the small intestine?
Answer: Hexoses and pentoses are rapidly absorbed across the wall of the small intestine and pass from mucosal cells to interstitial fluid, and then to capillary blood.
Qcard 9:
Question: What is the mechanism of glucose and galactose absorption in the small intestine?
Answer: Glucose and galactose are absorbed through a sodium-dependent glucose transporter (SGLT-1) that uses sodium's electrochemical gradient for active transport.
Qcard 10:
Question: How is fructose absorbed in the small intestine?
Answer: Fructose is transported by
Monosaccharides
Salivary a-Amylase
Intestinal Carbohydrate Digestion
Luminal Phase (Pancreatic a-Amylase)
Brush Border Phase (Oligosaccharidases)
Intestinal Monosaccharide Absorption
Hexoses and pentoses
No intestinal digestion required
Absorbed in the duodenum and jejunum
Initiates hydrolysis of a-1,4 glycosidic bonds
Digests glycogen and starch
Action inhibited by acidic gastric juice
Hormonal or pancreatic phase
Brush border membranes
Exoenzymes clip off one monosaccharide at a time
Stimulated by chyme entry into the duodenum
Secretin and cholecystokinin hormones released
Digestion of polysaccharides to dextrins and isomaltose
Enzymes in brush border membranes
Protected by glycocalix mucus coat
Hydrolysis of a-1,6 glycosidic linkages in isomaltose and dextrins
Rapid absorption of hexoses and pentoses
Active transport involving a carrier protein
Sodium-dependent glucose transporter (SGLT-1)
Fructose absorption through facilitated diffusion
Glucose and galactose absorption
Fructose absorption
Intestinal pentose absorption
Active transport driven by sodium's electrochemical gradient
Sodium-dependent glucose transporter (SGLT-1)
Insulin-independent GLUT-2 transporter
Facilitated diffusion
GLUT-5 transporter
Transported out of enterocytes using GLUT-2 transporter
Passive diffusion
Read and understand the general concepts of carbohydrate digestion.
Focus on the role of monosaccharides, oligosaccharides, and their digestion.
Take notes on the different types of glycosidic linkages and their significance.
Study the function and optimal pH of salivary a-amylase (Ptyalin).
Understand the digestion of glycogen and starch in the mouth and upper small intestine.
Review the luminal phase of intestinal carbohydrate digestion.
Learn about the hormonal or pancreatic phase and the release of secretin and cholecystokinin.
Understand the role of pancreatic a-amylase in the digestion of starch, glycogen, and dextrins.
Study the products formed during the luminal phase, including isomaltose, maltose, and maltotriose.
Take note of the destruction of salivary and pancreatic a-amylase by trypsin activity.
Focus on the brush border phase of carbohydrate digestion.
Learn about the enzymes located in the brush border membranes and their saccharidase activity.
Understand the role of isomaltase, maltase, sucrase, and lactase in the digestion of different disaccharides.
Study the presence of glucocerebrosidase and glucoamylase in the brush border of the small intestine.
Take note of the inducibility of maltase and sucrase by their substrates.
Review the digestion of dietary disaccharides, including sucrose, lactose, and trehalose.
Understand the role of brush border galactocerebrosidase (lactase) in the digestion of lactose.
Study the digestion of dietary glucocerebrosides and the presence of glucoamylase in the brush border.
Take note of the difficulty in digesting leguminous seeds due to modified sucrose.
Focus on intestinal monosaccharide absorption.
Understand the absorption of hexoses and pentoses across the wall of the small intestine.
Study the role of the sodium-dependent glucose transporter (SGLT-1) in active glucose and galactose transport.
Learn about the absorption of fructose through facilitated diffusion
Chapter 38: Carbohydrate Digestion
Monosaccharides (largely hexoses and pentoses) require no intestinal digestion prior to absorption; however, oligosaccharides must be hydrolyzed to monosaccharides before they can be absorbed. Since mammals lack the enzyme cellulase, they are incapable of carrying out the constitutive digestion of cellulose (which contains b-1,4 glycosidic linkages). However, they can digest (i.e., hydrolyze) dietary starch and glycogen (which contain a-1,4 and a-1,6 glycosidic linkages). Sites for starch and glycogen digestion are in the mouth and upper small intestine. Most monosaccharide absorption occurs in the duodenum and jejunum.
Salivary a-Amylase (Ptyalin): With the exception of ruminants and carnivores (who do not secrete salivary a-amylase), this endo-glycosidase (or endo-glucosidase) initiates hydrolysis of a-1,4 glycosidic bonds within dietary glucose polymers, (e.g., glycogen and starch), but it will not attack a-1,6 or terminal a-1,4 glycosidic linkages. Glycogen is a product of animal metabolism, whereas starch is the comparable plant storage form of glucose. Glucose molecules in glycogen are mostly in long chains held together by a-1,4 glycosidic bonds, but there is some chain-branching produced by a-1,6-linkages. Amylopectin, which constitutes 80-85% of dietary starch, is similar but less branched, whereas amylose, the other component of starch, is a straight chain glucose polymer containing only a-1,4 linkages.
Oligosaccharides are products of salivary a-amylase digestion. The major oligosaccharides are dextrins (with a-limit dextrins being the first formed products), compounds with an average chain length of 8-10 glucose residues containing the a-1,6 branches. Small amounts of maltose (an a-1,4 disaccharide), and maltotriose (an a-1,4 trisaccharide) are also formed at this point. The optimal pH for salivary a-amylase is 6.7, and its action is inhibited by acidic gastric juice when food enters the stomach. Therefore, little starch and glycogen digestion occurs during the short time food is in the mouth, and even less will occur in the stomach unless it fails to mix its contents fully.
Intestinal Carbohydrate Digestion: There are two phases of intestinal carbohydrate digestion. The first occurs in the lumen of the small intestine, and is commonly referred to as the hormonal or pancreatic phase. The second occurs in brush border membranes, and involves the action of a number of integral membrane proteins with saccharidase activity. Unlike salivary and pancreatic a-amylase, most of the surface oligosaccharidases are exoenzymes which clip off one monosaccharide at a time.
Luminal Phase (Pancreatic a-Amylase): The entry of partially digested acidic chyme into the duodenum stimulates specialized mucosal cells to release two important polypeptide hormones into blood; secretin (from duodenal S cells), and cholecystokinin (CCK, from duodenal I cells). These hormones then stimulate exocrine pancreatic secretions into the duodenal lumen containing NaHCO3 (needed to neutralize acidic chyme), and digestive enzymes (including a-amylase). Both salivary and pancreatic a-amylase (which are similar enzymes), continue internal starch, glycogen, and dextrin digestion in a favorable neutral duodenal pH environment (i.e., pH. 7). Polysaccharides are digested to a mixture of dextrins and isomaltose (which contain all of the a-1,6 branch-point linkages), as well as maltose and maltotriose. Most salivary and pancreatic a-amylase is destroyed by trypsin activity in lower portions of the intestinal tract, although some amylase activity may be present in feces.
Brush Border Phase (Oligosaccharidases): Enzymes responsible for the final phase of carbohydrate digestion are located in brush border membranes of the small intestine, and have their active sites extending into the lumen. They are generally protected from degradation by a glycocalix mucus coat. However, since they are anaerobic enzymes, like all digestive enzymes, when they are cleaved from the brush border, or mucosal cells are sloughed into the lumen, these enzymes remain active. Some of these brush border enzymes have more than one substrate. Isomaltase (also called a-dextrinase or a-1,6-glucosidase), is mainly responsible for hydrolysis of a-1,6- glycosidic linkages in isomaltose and the dextrins. However, along with maltase (also called a-glucosidase) and sucrase (also called invertase), it also breaks down maltotriose and maltose. Sucrase/isomaltase is a bifunctional enzyme, having one domain with isomaltase activity, and another with sucrase activity on the same polypeptide. Sucrase and isomaltase are reportedly synthesized as a single polypeptide chain and inserted into the brush border membrane. This protein is then hydrolyzed by pancreatic proteases into sucrase and isomaltase subunits, but the subunits reassociate noncovalently at the intestinal surface.
Dietary disaccharides (sucrose, lactose, and trehalose) are digested by their appropriate disaccharidases. Trehalose is a rare disaccharide found in young mushrooms, and lactose, which is found in milk, generally disappears from the animal diet following weaning.
A brush border galactocerebrosidase (bgalactosidase or lactase) catalyzes digestion of dietary galactocerebrosides (galactosylceramides), as well as lactose (a glucose-galactose disaccharide). Although lactase is a labile enzyme, maltase and sucrase are more adaptive, and therefore inducible by their substrates.
A glucocerebrosidase (b-glucosidase) is also present in the brush border of the small intestine, which catalyzes digestion of dietary glucocerebrosides. Additionally, another member of the a-amylase family (i.e., enzymes found in a number of organs and tissues in addition to the pancreas and salivary glands (e.g., semen, testes, ovaries, fallopian tubes, striated muscle, lung, and adipose tissue), is present in the brush border of the small intestine. This enzyme, glucoamylase or exo a-1,4-glucosidase, catalyzes hydrolysis of terminal a-1,4-glycosidic bonds in starch, glycogen, and the dextrins.
In pancreatic insufficiency, as well in a variety of bacterial and enteric infections, transient loss of carbohydrate digestive activity can occur. As a result, increased amounts of di-, oligo-, and polysaccharides that are not hydrolyzed by a-amylase and/or intestinal brush border oligosaccharidases, cannot be absorbed: therefore, they reach the distal portion the intestine, which contains bacteria from the lower ileum on down. Bacteria can effectively metabolize carbohydrate polymers because they possess many more types of saccharidases than do mammals. Products of anaerobic bacterial carbohydrate digestion include short-chain volatile fatty acids, lactate, hydrogen gas (H2), methane (CH4), and carbon dioxide (CO2). These compounds, if not absorbed, can cause fluid secretion, increased intestinal motility, and cramps (i.e., diarrhea), either because of increased intraluminal osmotic pressure, distension of the gut, or because of a direct irritant effect of bacterial degradation products on the intestinal mucosa. Some leguminous seeds (e.g., beans, peas, soya) can also be difficult for some animals to digest since they contain a modified sucrose to which one or more galactose moieties are linked. The glycosidic bonds of galactose are in the a-configuration, which can only be split by bacterial enzymes. The simplest sugar of this family is raffinose (a Gal(1,6)-a Glc(1,2)-b Fru).
Intestinal Monosaccharide Absorption: Hexoses and pentoses are rapidly absorbed across the wall of the small intestine. Essentially all are removed before remains of a meal reach the terminal part of the ileum. Monosaccharides pass from mucosal cells to interstitial fluid, and then to capillary blood that drains into the hepatic portal vein. The mucosal cell process involves movement across the apical membrane on the luminal side, and the basolateral membrane on the serosal side of the cell.
Early experiments concerning absorption rates for glucose from solutions perfused through the intestines of guinea pigs, showed that the bulk of glucose absorption is oxygen dependent. Therefore, it was concluded that active transport is involved, and that only a small amount of glucose is normally absorbed via a passive, diffusional mechanism. In order to explain how the active component occurs, a carrier has been identified which binds both glucose and Na+ at separate sites, and which transports them both through the apical membrane using sodium's electrochemical gradient. Both glucose and galactose transport are uniquely affected by the amount of Na+ in the intestinal lumen because they share, with Na+, the same cotransporter, or symport, and therefore compete for uptake. This transporter, known as the sodium-dependent glucose transporter (SGLT-1), is also found in apical membranes of proximal renal tubular epithelial cells. It is insulin-independent, does not require ATP (directly), and can transport these sugars (but not Na+) against their concentration gradients.
Since the intracellular Na+ concentration is low in intestinal and proximal renal tubular epithelial cells, as it is in other cells, Na+ moves into the cell along its concentration gradient. Glucose or galactose moves with Na+ , with release occurring inside the cell. The Na+ is then actively transported into the lateral inter[1]cellular space (in a 3:2 exchange with K+), and glucose and/or galactose are transported by facilitated diffusion, using an insulin-inde[1]pendent GLUT-2 transporter, into the interstitium and thence into capillary blood. Thus, Na+ /glucose/galactose cotransport is an example of secondary active transport, with energy from ATP used to drive Na+ /K+ ATPase. Once Na+ reaches lateral intercellular spaces, it is free to diffuse down its concentration gradient, either back into the lumen or toward blood. When the apical Na+ /glucose/galactose cotransporter is congenitally defective, resulting glucose/galactose malabsorption causes severe diarrhea that can be fatal if glucose and galactose are not promptly removed from the diet.
Fructose utilizes a slightly different mechanism for intestinal absorption. The rate of fructose absorption is generally about 3 to 6 times slower than that of overall glucose absorption, and it is not apparently driven by a secondary-active mechanism. It is, however, saturable. Fructose is transported by Na+ -independent facilitated diffusion into enterocytes (along with some glucose and galactose), using the insulin-independent GLUT-5 transporter. It is transported out of enterocytes, along with glucose and galactose, using the GLUT-2 transporter. Some fructose is converted to glucose inside mucosal cells. Additionally, glucose (and fructose) can also enter into intracellular metabolism. About 10% of available glucose is thought to enter the hexose monophosphate shunt of enterocytes. Since mucosal cells have a high rate of glycolysis, the lactate so produced anaerobically diffuses into portal blood where it can be extracted and metabolized by the liver.
Intestinal pentose absorption is thought to occur by simple passive diffusion, and is not apparently associated with the SGLT or GLUT transporters. The molecular configurations that appear to be necessary for the secondary active transport of monosaccharides by the SGLT-1 transporter are the following: The OH on carbon 2 should have the same configuration as that in glucose, and an a-pyranose ring must be present. Both of these conditions are present in the hexoses glucose and galactose, but not in fructose.
SUMMARY
Chapter 38 discusses carbohydrate digestion in mammals. Monosaccharides, such as hexoses and pentoses, do not require digestion before absorption. However, oligosaccharides need to be hydrolyzed into monosaccharides before absorption. Mammals lack the enzyme cellulase, so they cannot digest cellulose. They can digest dietary starch and glycogen, which contain different glycosidic linkages. Starch and glycogen digestion occurs in the mouth and upper small intestine. Salivary a-amylase initiates the digestion of starch and glycogen. In the small intestine, there are two phases of carbohydrate digestion: the luminal phase and the brush border phase. In the luminal phase, pancreatic a-amylase continues the digestion of starch, glycogen, and dextrins. In the brush border phase, various enzymes in the brush border membranes of the small intestine break down oligosaccharides into monosaccharides. Hexoses and pentoses are rapidly absorbed in the small intestine, and their absorption is dependent on active transport. Glucose and galactose are transported using a sodium-dependent glucose transporter, while fructose is transported through facilitated diffusion. Pentose absorption occurs through passive diffusion.
OUTLINE
I. Monosaccharides
Monosaccharides (hexoses and pentoses) do not require intestinal digestion before absorption
Oligosaccharides must be hydrolyzed to monosaccharides before absorption
Mammals lack cellulase enzyme, cannot digest cellulose
Can digest dietary starch and glycogen
II. Salivary a-Amylase
Initiates hydrolysis of a-1,4 glycosidic bonds in glycogen and starch
Does not attack a-1,6 or terminal a-1,4 glycosidic linkages
Optimal pH is 6.7
Action inhibited by acidic gastric juice in the stomach
III. Intestinal Carbohydrate Digestion
Two phases: luminal phase and brush border phase
Luminal phase: pancreatic a-amylase continues digestion in duodenum
Polysaccharides digested to dextrins, isomaltose, maltose, and maltotriose
Brush border phase: exoenzymes in brush border membranes hydrolyze oligosaccharides
IV. Intestinal Monosaccharide Absorption
Hexoses and pentoses rapidly absorbed in small intestine
Active transport involved, glucose and galactose transported with Na+
Sodium-dependent glucose transporter (SGLT-1) responsible for transport
Fructose absorbed by facilitated diffusion using GLUT-5 transporter
Pentose absorption occurs by passive diffusion
V. Disorders and Malabsorption
Pancreatic insufficiency and bacterial infections can cause loss of carbohydrate digestive activity
Bacteria metabolize carbohydrates, produce compounds that can cause diarrhea
Some leguminous seeds and congenital defects can lead to malabsorption
Fructose absorption slower and different mechanism compared to glucose and galactose
QUESTIONS
Qcard 1:
Question: What is the process by which monosaccharides are absorbed in the small intestine?
Answer: Monosaccharides pass from mucosal cells to interstitial fluid, and then to capillary blood that drains into the hepatic portal vein.
Qcard 2:
Question: What is the role of salivary a-amylase in carbohydrate digestion?
Answer: Salivary a-amylase initiates hydrolysis of a-1,4 glycosidic bonds within dietary glucose polymers, such as glycogen and starch.
Qcard 3:
Question: What are the major oligosaccharides formed during salivary a-amylase digestion?
Answer: The major oligosaccharides formed are dextrins, with a-limit dextrins being the first formed products.
Qcard 4:
Question: What is the optimal pH for salivary a-amylase?
Answer: The optimal pH for salivary a-amylase is 6.7.
Qcard 5:
Question: What are the two phases of intestinal carbohydrate digestion?
Answer: The first phase occurs in the lumen of the small intestine, and the second phase occurs in brush border membranes.
Qcard 6:
Question: What is the role of pancreatic a-amylase in carbohydrate digestion?
Answer: Pancreatic a-amylase continues the digestion of starch, glycogen, and dextrins in the duodenum.
Qcard 7:
Question: What are the enzymes responsible for the final phase of carbohydrate digestion?
Answer: Enzymes located in the brush border membranes of the small intestine, such as isomaltase, maltase, and sucrase, are responsible for the final phase of carbohydrate digestion.
Qcard 8:
Question: How are hexoses and pentoses absorbed in the small intestine?
Answer: Hexoses and pentoses are rapidly absorbed across the wall of the small intestine and pass from mucosal cells to interstitial fluid, and then to capillary blood.
Qcard 9:
Question: What is the mechanism of glucose and galactose absorption in the small intestine?
Answer: Glucose and galactose are absorbed through a sodium-dependent glucose transporter (SGLT-1) that uses sodium's electrochemical gradient for active transport.
Qcard 10:
Question: How is fructose absorbed in the small intestine?
Answer: Fructose is transported by
Monosaccharides
Salivary a-Amylase
Intestinal Carbohydrate Digestion
Luminal Phase (Pancreatic a-Amylase)
Brush Border Phase (Oligosaccharidases)
Intestinal Monosaccharide Absorption
Hexoses and pentoses
No intestinal digestion required
Absorbed in the duodenum and jejunum
Initiates hydrolysis of a-1,4 glycosidic bonds
Digests glycogen and starch
Action inhibited by acidic gastric juice
Hormonal or pancreatic phase
Brush border membranes
Exoenzymes clip off one monosaccharide at a time
Stimulated by chyme entry into the duodenum
Secretin and cholecystokinin hormones released
Digestion of polysaccharides to dextrins and isomaltose
Enzymes in brush border membranes
Protected by glycocalix mucus coat
Hydrolysis of a-1,6 glycosidic linkages in isomaltose and dextrins
Rapid absorption of hexoses and pentoses
Active transport involving a carrier protein
Sodium-dependent glucose transporter (SGLT-1)
Fructose absorption through facilitated diffusion
Glucose and galactose absorption
Fructose absorption
Intestinal pentose absorption
Active transport driven by sodium's electrochemical gradient
Sodium-dependent glucose transporter (SGLT-1)
Insulin-independent GLUT-2 transporter
Facilitated diffusion
GLUT-5 transporter
Transported out of enterocytes using GLUT-2 transporter
Passive diffusion
Read and understand the general concepts of carbohydrate digestion.
Focus on the role of monosaccharides, oligosaccharides, and their digestion.
Take notes on the different types of glycosidic linkages and their significance.
Study the function and optimal pH of salivary a-amylase (Ptyalin).
Understand the digestion of glycogen and starch in the mouth and upper small intestine.
Review the luminal phase of intestinal carbohydrate digestion.
Learn about the hormonal or pancreatic phase and the release of secretin and cholecystokinin.
Understand the role of pancreatic a-amylase in the digestion of starch, glycogen, and dextrins.
Study the products formed during the luminal phase, including isomaltose, maltose, and maltotriose.
Take note of the destruction of salivary and pancreatic a-amylase by trypsin activity.
Focus on the brush border phase of carbohydrate digestion.
Learn about the enzymes located in the brush border membranes and their saccharidase activity.
Understand the role of isomaltase, maltase, sucrase, and lactase in the digestion of different disaccharides.
Study the presence of glucocerebrosidase and glucoamylase in the brush border of the small intestine.
Take note of the inducibility of maltase and sucrase by their substrates.
Review the digestion of dietary disaccharides, including sucrose, lactose, and trehalose.
Understand the role of brush border galactocerebrosidase (lactase) in the digestion of lactose.
Study the digestion of dietary glucocerebrosides and the presence of glucoamylase in the brush border.
Take note of the difficulty in digesting leguminous seeds due to modified sucrose.
Focus on intestinal monosaccharide absorption.
Understand the absorption of hexoses and pentoses across the wall of the small intestine.
Study the role of the sodium-dependent glucose transporter (SGLT-1) in active glucose and galactose transport.
Learn about the absorption of fructose through facilitated diffusion
