Biochemistry and Human Nutrition

Module 4. Human nutrition

Lesson 29
DIGESTION AND ABSORPTION OF CARBOHYDRATES, LIPIDS AND PROTEINS

29.1 Introduction

• Our normal food is a mixture of complex plant and animal materials that is composed largely of carbohydrates, fat, protein, vitamins, and minerals.
• The bulk of these ingested nutrients consist of large polymers that must be reduced to simpler components before they can be absorbed and thus made available to all the cells in the body.
• The disintegration of naturally occurring food stuffs into assimilable forms in the gastrointestinal tract constitutes the process of digestion and involves enzymes.
• The gastrointestinal tract constitutes the process of digestion and involves enzymes. The majority of the enzymes involved in the digestive process are hydrolases (i.e., they split bonds of esters, glycosides, or peptides by the addition of water).
• The powerful hydrolytic enzymes of the digestive tract catalyze the degradation of large molecules present in food (e.g., starch or protein) into small molecules that can be readily absorbed such as glucose or amino acids. (Video: Human digestive system, Source: Youtube)
  

29.2 Digestion

• Food is taken through mouth where it is homogenized, mixed, and lubricated by saliva secreted by salivary glands. One constituent of human saliva is amylase which catalyses the hydrolysis of starch. Approximately 1.5 L of saliva is secreted daily.
• From the mouth the food contents pass via the esophagus to the stomach where they come in contact with gastric juice with a pH ≤ 2. Gastric juice contains hydrochloric acid, mucins, and the enzymes pepsin and lipase. Hydrochloric acid is secreted by parietal cells and pepsin by the chief cells. Chyme, the acidic food content in the stomach, is intermittantly introduced into the small intestine.
• The alkaline content of pancreatic (about 1.5 L/day) and biliary secretions (0.5 L/day) neutralize the acid of the chyme and change the pH to the alkaline side necessary for the optimum activity of pancreatic and intestinal enzymes.
• Most of the breakdown of food is catalyzed by the soluble enzymes and occurs within the lumen of the small intestine; however, the pancreas is the major organ that synthesizes and secretes the large amounts of enzymes needed to digest the food. Secreted enzymes amount to about 30 g/day of protein in a healthy adult. The pancreatic duct joins with the common bile duct to form the ampulla of Vater; thus, pancreatic juice and bile empty into the duodenum at the same point.

Table 29.1 Gastrointestinal hormones

• When fat and digestion products of protein reach the small intestine, the duodenal and jejunal mucosa release cholecystokinin, a peptide hormone. It stimulates the secretion of pancreatic juice rich in enzymes and also stimulates the contraction of the gall bladder and secretion of bile.
• The presence of acidic food in the small intestine causes the release of another peptide hormone, secretin, by the duodenal and jejuna mucosa; this stimulates secretion of pancreatic juice rich in bicarbonate and potentiates the action of cholecystokinin on the pancreas.
• The secretion of gastric juice is under the control of the hormone gastrin, a heptadecapeptide and its release is stimulated by the presence of food in the stomach. Gastrin is secreted by the antral region of the gastric mucosa and by the duodenal mucosa. The main function of gastrin is to stimulate the secretion of hydrochloric acid into the stomach, but it also stimulates pepsin secretion and increases the motility of the gastric antrum. Site of secretion and biological activity these hormones are summarized in Table 29.1.
• At the low pH of the gastric juice, proteins are denatured and this allows the polypeptide chains to unfold and makes them more accessible to the action of proteolytic enzymes. Some digestion of protein occurs within the lumen of the stomach and the acid environment also destroys most of the microorganisms swallowed or ingested with food. An average of 2-2.5 L/day of gastric juice is secreted, but the volume is reduced in atrophy of the gastric glands.
• The bulk of digestion occurs distal to the second (descending) part of the duodenum. The final result of the action of digestive enzymes is to reduce the nutrients to form that can be absorbed and assimilated. There is little absorption of nutrients from the stomach although alcohol can be absorbed to a significant extent by this organ. Even water passes through the stomach to be absorbed subsequently in the intestine. The main organ for the absorption of nutrients is the small intestine which has sites for the absorption of specific nutrients.

29.3 Carbohydrates

• The digestion of starch begins in the mouth when the food is mixed with salivary α-amylase but the hydrolysis stops in the stomach because of the change in pH and resumes in the duodenum where pancreatic α-amylase is secreted. Both salivary and pancreatic amylase are α-1, 4 glucosidases and serve to hydrolyze only the internal 1, 4 glucosidic bonds found in starch and glycogen. There is little activity at the 1, 4- linkages adjacent to the branching points, and the α-1, 6 bonds (or branch points) are not attached by amylase.
• Consequently, the products of digestion by α-amylase on starch or glycogen are maltose, isomaltose, maltotriose (a trisaccharide), and α-limit dextrins (containing on the average 8 glucose units with one or more α-1, 6 bonds). The final digestive process occurs at the mucosal lining and involves the action of α-dextrinase (isomaltase) which hydrolyzes the 1, 6 glucosidic bonds from limit dextrins and isomaltose.
• Maltase, another brush-border enzyme, breaks down maltose and maltotriose to glucose which is the end product of starch and glycogen digestion.
• Sucrose and lactose are similarly hydrolyzed by sucrase and lactase that are located on the brush border to their corresponding monosaccharides glucose and fructose, and glucose and galactose, respectively.
• Monosaccharides are absorbed from the intestinal lumen by passage through the mucosal epithelial cells into the blood stream.
• The transport of glucose and galactose across the brush border membrane of the mucosal cell occurs by an active, energy-requiring process that involves a specific transport protein and the presence of sodium ions.
• Fructose is absorbed by a facilitated diffusion process. Other sugars (e.g., pentoses) are absorbed by simple diffusion through the lipid bilayer of the membrane. In the normal individual, the digestion and absorption of usable carbohydrates are 95% or more complete.

29.4 Lipids

• Lipids include a wide variety of chemical substances such as neutral fat (e.g., triglycerides), fatty acids and their derivatives, phospholipids, glycolipids, sterols, carotenes, and fat-soluble vitamins. Fat constitutes about 90% of dietary lipids and provides energy in a highly concentrated form. It accounts for 40-45% of the total daily energy intake (100 g/day in the average western diet).
• The digestion of fat and other lipids poses a special problem because they are insoluble in water while the lipolytic enzymes, like other enzymes, are soluble in aqueous medium. The problem is solved by emulsification which is the intimate admixture of two phases, one dispersed in the other as fine droplets or micelles. In this context the two phases are water and fat, the later making up the micelles.
• Micelles tend to aggregate if they are not stabilized in some way; in the duodenum this role is performed by the bile salts. A bile salt molecule has two sides, one is hydrophobic and the other hydrophilic. So one side tends to be associated with aqueous phase and the other with lipid phase. Such molecules are said to be amphipathic and are powerful emulsifying agents.
• Little or no lipid digestion occurs in the mouth. There is some lipase in the stomach but the acidic environment and the absence of bile salts prevents any significant digestion of fat in this organ.
• The forceful contraction of the stomach (antrum) breaks up lipids into fine droplets and in the duodenum these droplets are exposed to the solubilizing effects of bile salts. A fat globule which has an average diameter of about 100 is reduced several fold after emulsification and the surface area is amplified about 10,000 times.
• Lipolytic enzymes cannot penetrate the lipid droplets, but function at the lipid-water interface. Emulsified triglycerides are readily attacked by lipase secreted in pancreatic juice. The bile salts and phospholipids present in bile normally adhere to the surface of triglyceride droplets, thereby displacing lipase from its substrate.
• Colipase (a small protein with a molecular weight of 10,000) which binds to both the water-lipid interface and to lipase, thereby anchoring and activating the enzyme. Colipase is secreted by the pancreas as procolipase (inactive) simultaneously with lipase in a 1:1 ratio and is activated by trypsin hydrolysis of an arginyl-glycyl bond in N-terminal region and removal of a small group (<12) of amino acids.
• Pancreatic lipase attacks the ester linkages at the 1- and 3-carbons of the triglyceride, leaving a monoglyceride with the fatty acid esterified at the 2-carbon position of glycerol. This linkage can be cleaved by an esterase to release the third fatty acid molecule and glycerol, but is not a necessary step for absorption.
• Monoglycerides, along with bile salts, play an important role in stabilizing and further increasing the emulsification of lipid in the small intestine. The emulsified lipid droplets (micelles) are further reduced in size which enhances the digestion of fats and other lipids solubilized in the micellar particles.
• Several other enzymes secreted in the pancreatic juice are involved in the digestion of certain lipids. For example, cholesterol esterase hydrolyzes cholesterol esters to cholesterol and fatty acids. Another less specific lipid esterase acts on short-chain triglycerides, monoglycerides or other lipid esters (e.g., esters of vitamin A) with fatty acids.
• Phospholipids are hydrolyzed by phospholipase A2 which is secreted as proenzyme (inactive) and is activated by trypsin. Phospholipase A2 releases the fatty acid at 2-carbon of the phospholipid leaving a lysophospholipid.
• In normal individuals lipid absorption occurs in the upper part of the small intestine. Monoacylglycerol, fatty acids, and cholesterol leave the micelles at the brush border of the epithelial cells of the intestinal mucosa and pass through the cell membrane by passive diffusion.
• The fate of the absorbed fatty acids depends on their size. Those with less than 10-12 carbon atoms pass directly from the mucosal cells into portal blood and are bound to albumin for transport as unesterified (free) fatty acids.
• The large fatty acids are reesterified with monoacylglycerol to the triglyceride level in the smooth endoplasmic reticulum. Some of the cholesterol that enters the mucosal cells from the micelles is also esterified. The newly synthesized triglycerides and cholesterol esters are complexed with a specific protein, cholesterol, and phospholipids to produce particles called chylomicrons which are released from the mucosal cells by exocytosis and enter the lymph.
• The bile salts do not cross the mucosal barriers into the lymphatic system. Instead, they are reabsorbed in micellar form in the lower segment of the small intestine and are returned to the liver by the portal vein. This route is part of enterohepatic circulation and permits the bile salts to be salvaged for resecretion into the bile.

29.5 Proteins

• The total daily protein load to be digested includes about 70-100 g of dietary protein and 35-200 g of endogenous protein from digestive enzymes and sloughed cells.
• The overall process of proteolysis must occur without the body’s own protein being digested. A protected compartment for the hydrolytic process is provided by the lumen of the gastrointestinal tract.
• In addition, the secretory cells that synthesize proteases (except dipeptidases and aminopeptidases) are protected because these enzymes are formed and sequestered in storage granules in inactive forms, the zymogens, until needed.
• The subsequent transformation of the zymogens to the active enzymes occurs largely in the lumen of the gastrointestinal tract and involves, in part, changes in the molecular conformation. In almost all cases, a relatively small masking peptide is split off from the zymogen, which results in a catalytically active species of proteolytic enzyme.
• Protein digestion can be divided into gastric, pancreatic, and intestinal phases, depending on the tissue source of the enzymes.

29.5.1 Gastric phase

The digestion begins in the stomach where protein is denatured by low pH and is exposed to the action of proteolytic enzymes. The acidic environment also provides the optimum pH for pepsin activity. The zymogen pepsinogen, which is secreted by chief cells, is converted to pepsin in the acid medium (autoactivation) or by active pepsin (autocatalysis) by removal of a peptide consisting of 44 amino acids from N-terminus. Although pepsin has a broad specificity, it attacks primarily peptide linkages in which the carboxyl group is donated by aromatic amino acid residues. Pepsin is an endopeptidase and the products of its action consist of a mixture of oligopeptides.

29.5.2 Pancreatic phase

The proteolytic enzymes are synthesized in the acinar cells of the pancreas and secreted in pancreatic juice as zymogens. These include trypsinogen, chymotrypsinogen, proelastase, and the procarboxypeptidases. In the lumen of the small intestine, enteropeptidase (which used to be called enterokinase), a protease produced by duodenal epithelial cells, activates trypsinogen to trypsin (by scission of the hexapeptide). Trypsin, in turn, activates trypsinogen, chymotrypsinogen, proelastase, and the procarboxypeptidases to their respective active enzymes. Trypsin, chymotrypsin, and elastase are endopeptidases. Trypsin is specific for peptide linkages in which carboxyl is donated by arginine or lysine. The specificity of chymotrypsin is similar to pepsin. Elastase has a rather broad specificity in attacking bonds next to small amino acids such as glycine, alanine and serine. Carboxypeptidases A and B attack the carboxyl-terminal peptide bonds, thereby liberating single amino acids. The combined action of pancreatic peptidases results in the formation of free amino acids and small peptides of 2-8 amino acid residues.

29.5.3 Intestinal phase

The luminal surface of small intestinal epithelial cells contain amino peptidase and dipeptidases. The end products of cell surface digestion are amino acids and di- and tripeptides. These are absorbed by the epithelial cells via specific amino acid or peptide transport systems. The di- and tripeptides are hydrolyzed within the cytoplasmic components before they leave the cell. The hydrolysis of most proteins is thus complete to their constituent amino acids.

After active absorption by the intestinal mucosal cells, the amino acids are taken up primarily by the blood capillaries in the mucosa and are transported in the plasma to the liver and other tissues for metabolic use. A significant amount of the absorbed amino acids also appear in the lymph. The digestion and absorption of the majority of dietary proteins is about 95% complete in the normal human subject.