DIGESTION, ABSORPTION, AND TRANSPORT OF
THE MAJOR DIETARY CARBOHYDRATES

Carbohydrates comprise approximately 40 to 45% of the caloric intake in the average western diet. The major carbohydrates consumed are starches, sucrose, maltose and lactose. Plant starches, polysaccharides containing tens of thousands to a million glucosyl units, comprise approximately 50 to 60% of the carbohydrate calories consumed.

Dietary polysaccharides and disaccharides are converted in the digestive tract to monosaccharides by glycosidases and then enter the bloodstream. Undigested carbohydrates enter the colon, where they may be fermented by bacteria.

The digestion of starch beings in the mouth by the action of salivary α-amylase, an endoglucosidase that hydrolyzes internal α-1,4 bonds between glucosyl residues at random intervals to yield shortened polysaccharide chains called α-dextrins. Salivary α-amylase is largely inactivated by the acidity of the stomach. The exocrine pancreas secretes bicarbonate, which neutralizes the acid, and digestive enzymes into the duodenum, including pancreatic α-amylase, which continues to hydrolyze starches and glycogen to the disaccharide maltose, the trisaccharide maltotriose and oligosaccharides called limit dextrins of between four and nine glucosyl residues. The two glucosyl residues linked by α-1,6 bonds eventually become isomaltose. α-amylase has no activity against α-1,6 glycosidic bonds and little activity against α-1,4 bonds at the reducing end of the chain.

Several intestinal brush border glycosidases digest the products of α-amylase to monosaccharides that can be transported into the enterocytes that line the small intestine and subsequently into the blood (absorption).

The disaccharide sucrose, and small amounts of the monosaccharides glucose and fructose are the major natural sweeteners in fruit, honey and vegetables. Most foods derived from animals, such as meat or fish, contain little carbohydrate except for a small amount of glycogen. The major dietary carbohydrate of animal origin is lactose, a disaccharide of glucose and galactose, present in milk and milk products. Sucrose is hydrolyzed to its monosaccharide components, glucose and fructose, by the sucrase-maltase catalytic site of the sucrase-isomaltase complex, which also has maltase activity (the isomaltase-maltase site of the complex accounts for almost all of the intestine’s ability to hydrolyze α-1,6 glycosidic bonds, as well as maltose). This complex account for 80% of the maltase activity of the small intestine, the remainder being present in the glucoamylase complex.

Lactose is hydrolyzed to its component monosaccharides, galactose and glucose, by the lactase catalytic site of the β-galactosidase complex (the major activity of the other catalytic site in humans is the hydrolysis of the β-bond between glucose or galactose and ceramide in glycolipids, which is hydrolyzed by the glucosyl-ceramidase). Lactose intolerance (hypolactasia) is a condition of pain, nausea, and flatulence after the ingestion of foods containing lactose, most notably dairy products, and results from insufficient lactase. Lactase activity increases in humans from about six to eight weeks of gestation and raises during the late gestational period (27-32 weeks). It remains high for about one month after birth and then begins to decline. Adults have less than 10% the lactase activity present in infants and adult levels are reached in most of the world’s population by the age of five to seven years. However, in people of western Northern European ancestry and milk-dependent Nomadic tribes of Saharan Africa the levels of lactase remain at, or slightly below, infant levels throughout adulthood.

The production of maltose, maltotriose, and limit dextrins by pancreatic α-amylase occurs in the duodenum. Sucrase-isomaltase activity and β-glycosidase activity are highest in the jejunum. Glucoamylase activity increases progressively along the length of the small intestine, and is highest in the ileum.

Some starches, particularly those high in amylose or less well hydrated (e.g., starch in dried beans), are not well digested and enter the colon where colonic bacteria metabolize them, producing gases, short-chain fatty acids, and lactate. The major short chain fatty acids are acetic acid ( two carbons), propionic acid (three carbons) and butyric acid (four carbons). They are absorbed by the colonic mucosal cells where they can provide a substantial energy source. Some of these fatty acids may travel to the liver through the hepatic portal vein.

The hexoses, glucose, galactose and fructose, are polar molecules that require transporter proteins for entry into and exit from cells. Two distinct groups of hexose transporters have been identified and classified based on their dependence on cellular energy: GLUTs, facilitative GLUcose Transporters, transport hexoses down a concentration gradient and do not require an input of energy. SGLUT1, a Sodium GLUcose co-Transporter located at the apical side of the enterocyte and on absorptive cells of the kidney, and SGLUT2, located on the absorptive cells of the kidney, transport glucose and galactose against a concentration gradient.

This transport requires an energy-dependent electrochemical gradient of sodium. Two sodium ions are co-transported with each hexose molecule. Sodium ions are pumped out of the cell by a membrane ATP-dependent ion pump (active transporter), which maintains the sodium gradient by exchanging three sodium ions for two potassium ions − the ”sodium-potassium ATPase”. The energy expended by this ATPase allows the enterocyte to transport glucose and galactose against a concentration gradient (lower concentration in the intestinal lumen, higher concentration in the enterocyte). Fructose is transported across the apical enterocyte membrane by GLUT5, which was initially classified as a glucose tansporter because of its amino acid sequence similarity to known GLUTS, but was subsequently identified functionally as a fructose transporter. The hexoses are transported out of the enterocyte at its basal-lateral side by another GLUT family member, GLUT2, into the interstitial space from which they are taken into the bloodstream by the portal vein.

GLUTS are integral membrane glycoproteins (sugar molecules covalently attached) with 12 membrane-spanning domains that transport hexoses between cells and the blood. SGLUT1 and SGLUT2 are not members of the GLUT family. Several GLUT isoforms, all perform a similar function, the transport of glucose in and out of cells, but different GLUTS have different Kms and Vmaxs and are expressed in different cell types commensurate with different cell-type-specific uses of glucose. For example, GLUT2, which has a high Km (low affinity for glucose) and a high Vmax (high capacity for glucose transport), is the major GLUT in the liver and pancreatic β cells.

The liver does not depend on glucose as an energy source, but rather, uses glucose mainly as a source of carbons for the synthesis of other molecules, most notably the energy storage molecules triacylglycerol (fats) and glycogen, when blood glucose is abundant from the diet soon after a meal. When dietary glucose is scarce, several hours after a meal, the liver does not use carbon from glucose to synthesize triacylglycerols or glycogen, as this would deplete blood glucose and deprive other glucose-dependent tissues of their essential energy source. Rather, the liver hydrolyzes its glycogen stores and synthesizes glucose from non-carbohydrate sources for export to maintain blood glucose homeostasis (at ~ 5mM). GLUT2, with its high Km and a high Vmax, is well suited to the liver’s use of glucose. Its high Km limits glucose entry into the liver when blood glucose is low. Its high Vmax allows rapid entry of glucose into the liver when blood glucose is high. In contrast, the brain is a glucose-dependent tissue and its neurons have GLUT3 with a low Km (high affinity for glucose), which ensures that the brain receives the glucose it requires for its survival, even when blood glucose concentration declines below normal.