MED1002 Absorption of Nutrients and Water PDF

Absorption of nutrients and water Learning Outcomes Describe the absorptive process of monosaccharides that are formed as a result of digestion of carbohydrates Describe mechanisms of absorption of amino acids Describe the role of bile acids in the absorption of fats Describe the role of emulsificat...

Absorption of nutrients and water Learning Outcomes Describe the absorptive process of monosaccharides that are formed as a result of digestion of carbohydrates Describe mechanisms of absorption of amino acids Describe the role of bile acids in the absorption of fats Describe the role of emulsification and micelle formation in the absorption of fats Define the role of the lymphatic system in the absorption of fats Describe mechanisms of nucleic acid absorption Describe mechanisms of vitamin absorption Describe absorptive process of vitamin B12 and name the related proteins Define the role of intestinal flora in the synthesis of vitamin K. Describe mechanisms of mineral (calcium, iron, magnesium) absorption Describe major absorptive processes that take place in the colon Describe the mechanisms of water absorption Absorption Absorption is the movement of substances (nutrients, water, electrolytes) from the lumen of the GI tract to the extracellular fluid. The digestive processes for carbohydrates, proteins, and lipids result in the conversion of dietary nutrients to chemical forms for which intestinal absorptive processes exist. As a consequence, the digestive-absorptive processes for the several dietary constituents are closely integrated and regulated biological events that ensure survival. Sites of nutrient absorption. A, The entire small intestine absorbs carbohydrates, proteins, and lipids. However, the absorption is greatest in the duodenum, somewhat less in the jejunum, and much less in the ileum. The thickness of the arrows indicates the relative magnitude of total absorption at the indicated site in vivo. The maximal absorptive capacity of a specific segment under optimized experimental conditions (e.g., substrate concentrations) may be greater. B, Some substances are actively absorbed only in the duodenum. C, Bile acids are absorbed along the entire small intestine, but active absorption occurs only in the ileum. D, The vitamin cobalamin is absorbed only in the ileum. Medical Physiology: A Cellular and Molecular Approach 2e Multiple diseases can alter these digestive-absorptive processes and can thereby impair nutrient assimilation (i.e., the overall process of digestion and absorption). Because of the substantial segmental distribution of nutrient absorption along the gastrointestinal tract, the clinical manifestations of disease often reflect these segmental differences. Medical Physiology: A Cellular and Molecular Approach 2e The intestinal, pancreatic, and hepatic secretion of enzymes and bile is essential for normal digestive function. Although a significant amount of mechanical digestion takes place in the mouth and stomach, chemical digestion of food is limited to a small amount of starch breakdown and incomplete protein digestion in the stomach. When chyme enters the small intestine, protein digestion stops when pepsin is inactivated at the higher intestinal pH. Pancreatic and brush border enzymes then finish digestion of peptides, carbohydrates, and fats into smaller molecules that can be absorbed. Medical Physiology: A Cellular and Molecular Approach 2e Carbohydrates Most of the carbohydrate found in a typical diet is the plant polysaccharide starch (two-thirds)and most of the remainder consists of the disaccharides sucrose (table sugar) and lactose (milk sugar). Only small amounts of monosaccharides are normally present in the diet. Cellulose and certain other complex polysaccharides found in vegetable matter—referred to as fiber—cannot be broken down by the enzymes in the small intestine and are passed on to the large intestine, where bacteria partially metabolize them. Carbohydrates in food Carbohydrates The enzyme amylase breaks long glucose polymers into smaller glucose chains and the disaccharide maltose. Starch digestion starts in the mouth with salivary amylase but that enzyme is denatured in the acidic stomach. Pancreatic amylase then resumes digestion of starch into maltose. Maltose and other disaccharides are broken down by intestinal brushborder enzymes known as disaccharidases (maltase, sucrase, and lactase). The absorbable end products of carbohydrate digestion are glucose, galactose, and fructose. Carbohydrates break down into monosaccharides. Human Physiology: An Integrated Approach 8e Pearson, 2019 Amylopectin, which constitutes 80– 90% of dietary starch, is a branched molecule, whereas amylose is a straight chain with only 1:4α linkages. In the mouth, starch is attacked by salivary α-amylase. However, the optimal pH for this enzyme is 6.7, and its action is inhibited by the acidic gastric juice when food enters the stomach. In the small intestine, the salivary and the pancreatic α -amylase also act on the ingested polysaccharides. Both the salivary and the pancreatic α-amylases hydrolyze 1:4 α linkages but spare 1:6α linkages and terminal 1:4 α linkages. Consequently, the end products of α -amylase digestion are oligosaccharides: the disaccharide maltose; the trisaccharide maltotriose; and α-limit dextrins, polymers of glucose-containing an average of about eight glucose molecules with 1:6α linkages. The oligosaccharidases responsible for the further digestion of the starch derivatives are located in the brush border of small intestinal epithelial cells. Some of these enzymes have more than one substrate. Isomaltase is mainly responsible for hydrolysis of 1:6 α linkages. Along with maltase and sucrase, it also breaks down maltotriose and maltose. Sucrase and isomaltase are synthesized as a single glycoprotein chain inserted into the brush border membrane. It is then hydrolyzed by pancreatic proteases into sucrase and isomaltase subunits. The digestive process for dietary carbohydrates has two steps: (1) intraluminal hydrolysis of starch to oligosaccharides by salivary and pancreatic amylases, and (2) so-called membrane digestion of oligosaccharides to monosaccharides by brush-border disaccharidases. The resulting carbohydrates are absorbed by transport processes that are specific for certain monosaccharides. These transport pathways are located in the apical membrane of the smallintestinal villous epithelial cells. Carbohydrate absorption in the small intestine Human Physiology: An Integrated Approach 8e Pearson, 2019 Intestinal glucose and galactose absorption uses transporters the apical Na+glucose SGLT1 symporter and the basolateral GLUT2 transporter. Fructose absorption, however, is not Na+dependent. Fructose moves across the apical membrane by facilitated diffusion on the GLUT5 transporter and across the basolateral membrane by GLUT2 Medical Physiology: A Cellular and Molecular Approach 2e Lactose Intolerance Lactose, or milk sugar, is a disaccharide composed of glucose and galactose. Ingested lactose must be digested accomplished by the intestinal brush border enzyme lactase before it can be absorbed. Generally, lactase is found only in juvenile mammals, except in some humans of European descent. Those people inherit a dominant gene that allows them to produce lactase after childhood. Scientists believe the lactase gene provided a selective advantage to their ancestors, who developed a culture in which milk and milk products played an important role. In cultures where dairy products are not part of the diet after weaning, most adults lack the gene and synthesize less intestinal lactase. Decreased lactase activity is associated with a condition known as lactose intolerance. If a person with lactose intolerance drinks milk or eats dairy products, diarrhea may result. In addition, bacteria in the large intestine ferment lactose to gas and organic acids, leading to bloating and flatulence (intestinal gas). The simplest treatment for lactose intolerance is to remove milk products from the diet, although milk predigested with lactase is available. Protein Digestion Unlike carbohydrates, which are ingested in forms ranging from simple to complex, most ingested proteins are polypeptides or larger. Not all proteins are equally digestible by humans, however. Plant proteins are the least digestible. Among the most digestible is egg protein, 85–90% of which is in a form that can be digested and absorbed. Surprisingly, between 30% and 60% of the protein found in the intestinal lumen comes not from ingested food but from the sloughing of dead cells and protein secretions such as enzymes and mucus. Protein digestion begins with the action of pepsin in the stomach. The gastric chief cells secrete the inactive precursor of pepsin, pepsinogen. At lowgastric pH, pepsinogen is activated to pepsin. The first step in intestinal protein digestion is the activation of trypsinogen to its active form, trypsin, by the brush-border enzyme enterokinase. Initially, a small amount of trypsin is produced, which then catalyzes the conversion of all of the other inactive precursors to their active enzymes. Even the remaining trypsinogen is autocatalyzed by trypsin to form more trypsin. The activation steps yield five active enzymes for protein digestion: trypsin, chymotrypsin, elastase, carboxypeptidase A, and carboxypeptidase B. These pancreatic proteases then hydrolyze dietary protein to amino acids, dipeptides, tripeptides, and larger peptides called oligopeptides. Only the amino acids, dipeptides, and tripeptides are absorbable. The oligopeptides are further hydrolyzed by brushborder proteases, yielding smaller absorbable molecules The enzymes for protein digestion are classified into two broad groups: endopeptidases and exopeptidases. Endopeptidases, more commonly called proteases, attack peptide bonds in the interior of the amino acid chain and break a long peptide chain into smaller fragments. Proteases are secreted as inactive proenzymes (zymogens) from epithelial cells in the stomach, intestine, and pancreas. They are activated once they reach the GI tract lumen. Examples of proteases include pepsin secreted in the stomach, and trypsin and chymotrypsin secreted by the pancreas. Exopeptidases release single amino acids from peptides by chopping them off the ends, one at a time. Aminopeptidases act on the amino-terminal end of the protein; carboxypeptidases act at the carboxy-terminal end. The most important digestive exopeptidases are two isozymes of carboxypeptidase secreted by the pancreas. Aminopeptidases play a lesser role in digestion. Human Physiology: An Integrated Approach 8e Pearson, 2019 Peptide Absorption The primary products of protein digestion are free amino acids, dipeptides, and tripeptides, all of which can be absorbed. Most free amino acids are carried by Na+-dependent cotransport proteins. A few amino acid transporters are H+-dependent. Medical Physiology: A Cellular and Molecular Approach 2e The amino acids are transported from the lumen into the cell by Na+-amino acid cotransporters in the apical membrane, energized by the Na+ gradient. There are four separate cotransporters: one each for neutral, acidic, basic, and imino amino acids. The amino acids then are transported across the basolateral membrane into the blood by facilitated diffusion, again by separate mechanisms for neutral, acidic, basic, and imino amino acids. Dipeptides and tripeptides are carried into enterocytes on the oligopeptide transporter PepT1 that uses H+-dependent cotransport. Once inside the epithelial cell, these oligopeptides have two possible fates. Most are digested by cytoplasmic peptidases into individual amino acids, which are then transported across the basolateral membrane and into the circulation. Those oligopeptides that are not digested are transported intact across the basolateral membrane on an H+-dependent exchanger. The transport system that moves oligopeptides also is responsible for the intestinal uptake of certain drugs, including some antibiotics, angiotensin-converting enzyme inhibitors, and thrombin inhibitors Human Physiology: An Integrated Approach 8e Pearson, 2019 Neonates can absorb substantial amounts of intact protein from colostrum through the process of endocytosis. This mechanism is developmentally regulated and in humans remains active only until ~6 months of age. In adults, proteins are almost exclusively digested to their constituent amino acids and dipeptides, tripeptides, or tetrapeptides before absorption. However, even adults absorb small amounts of intact proteins. These absorbed proteins can be important in inducing immune responses to dietary proteins. Human Physiology: An Integrated Approach 8e Pearson, 2019 Lipid Digestion The dietary lipids include triglycerides, cholesterol, and phospholipids. A factor that greatly complicates lipid digestion and absorption is their insolubility in water (their hydrophobicity). Because the gastrointestinal tract is filled with an aqueous fluid, the lipids must somehow be solubilized to be digested and absorbed. The digestion of dietary lipids begins in the stomach with the action of lingual and gastric lipases and is completed in the small intestine with the actions of the pancreatic enzymes pancreatic lipase, cholesterol ester hydrolase, and phospholipase A2. Stomach The function of the stomach in lipid digestion is to churn and mix dietary lipids and to initiate enzymatic digestion. The churning action breaks the lipids into small droplets, increasing the surface area for digestive enzymes. In the stomach, the lipid droplets are emulsified (kept apart) by dietary proteins. (Bile acids, the primary emulsifying agents in the small intestine, are not present in the gastric contents.) Lingual and gastric lipases initiate lipid digestion by hydrolyzing approximately 10% of ingested triglycerides to glycerol and free fatty acids. One of the most important contributions of the stomach to overall lipid digestion (and absorption) is that it empties chyme slowly into the small intestine, allowing adequate time for pancreatic enzymes to digest lipids. The rate of gastric emptying, which is so critical to allow time for the subsequent intestinal digestive and absorptive steps, is slowed by CCK. CCK is secreted when dietary lipids first appear in the small intestine. Small intestine Most lipid digestion occurs in the small intestine, where conditions are more favorable than in the stomach. Bile salts are secreted into the lumen of the small intestine. These bile salts, together with lysolecithin and products of lipid digestion, surround and emulsify dietary lipids. Emulsification produces small droplets of lipid dispersed in the aqueous solution of the intestinal lumen, creating a large surface area for the action of pancreatic enzymes. The pancreatic enzymes (pancreatic lipase, cholesterol ester hydrolase, and phospholipase A2 ) and one special protein (colipase) are secreted into the small intestine to accomplish the digestive work. Human Physiology: An Integrated Approach 8e Pearson, 2019 Bile salts, are amphipathic, meaning that they have both a hydrophobic region and a hydrophilic region. The hydrophobic regions of bile salts associate with the surface of lipid droplets while the polar side chains interact with water, creating a stable emulsion of small, water-soluble fat droplets. Human Physiology: An Integrated Approach 8e Pearson, 2019 Enzymatic fat digestion is carried out by lipases, enzymes that remove two fatty acids from each triglyceride molecule. The result is one monoglyceride and two free fatty acids. The bile salt coating of the intestinal emulsion complicates digestion, however, because lipase is unable to penetrate the bile salts. For this reason, fat digestion also requires colipase, a protein cofactor secreted by the pancreas. Colipase displaces some bile salts, allowing lipase access to fats inside the bile salt coating. Human Physiology: An Integrated Approach 8e Pearson, 2019 Phospholipids are digested by pancreatic phospholipase. Free cholesterol is not digested and is absorbed intact. As enzymatic and mechanical digestion proceeds, fatty acids, bile salts, mono- and diglycerides, phospholipids, and cholesterol coalesce to form small disk-shaped micelles. Micelles then enter the unstirred aqueous layer at the edge of the brush border. Human Physiology: An Integrated Approach 8e Pearson, 2019 Fat Absorption Lipophilic fats such as fatty acids and monoglycerides are absorbed primarily by simple diffusion. They move out of their micelles and diffuse across the enterocyte membrane into the cells Human Physiology: An Integrated Approach 8e Pearson, 2019 Once monoglycerides and fatty acids are inside the enterocytes, they move to the smooth endoplasmic reticulum, where they recombine into triglycerides. The triglycerides then join cholesterol and proteins to form large droplets called chylomicrons. Because of their size, chylomicrons must be packaged into secretory vesicles by the Golgi. The chylomicrons then leave the cell by exocytosis. Human Physiology: An Integrated Approach 8e Pearson, 2019 The large size of chylomicrons also prevents them from crossing the basement membrane of capillaries. Instead, chylomicrons are absorbed into lacteals, the lymph vessels of the villi. Chylomicrons pass through the lymphatic system and finally enter the venous blood just before it flows into the right side of the heart. Some shorter fatty acids (10 or fewer carbons) are not assembled into chylomicrons. These fatty acids can therefore cross the capillary basement membrane and go directly into the blood. Human Physiology: An Integrated Approach 8e Pearson, 2019 Direct Absorption of Fatty Acids into the Portal Blood Small quantities of short- and medium-chain fatty acids, such as those from butterfat, are absorbed directly into the portal blood rather than being converted into triglycerides and absorbed by way of the lymphatics. Nucleic Acids The nucleic acid polymers DNA and RNA are only a very small part of most diets. They are digested by pancreatic and intestinal enzymes, first into their component nucleotides and then into nitrogenous bases and monosaccharides. The bases are absorbed by active transport, and the monosaccharides are absorbed by facilitated diffusion and secondary active transport, as other simple sugars are. Vitamins Vitamins are required in small amounts to act as coenzymes or cofactors for various metabolic reactions. Because vitamins are not synthesized in the body, they must be acquired from the diet and absorbed by the gastrointestinal tract. The vitamins are categorized as either fat-soluble or water-soluble. Fat-soluble vitamins The fat-soluble vitamins are vitamins A, D, E, and K. They are processed just like dietary lipids. In the intestinal lumen, fat-soluble vitamins are incorporated into micelles and transported to the apical membrane of the intestinal cells. They diffuse across the apical membrane into the cells, are incorporated in chylomicrons, and then are extruded into lymph, which delivers them to the general circulation. Water-soluble vitamins B1, B2 , B6 , B 12 , and C; biotin; folic acid; nicotinic acid; and pantothenic acid. In most cases, absorption of the water-soluble vitamins occurs via a Na+ -dependent cotransport mechanism in the small intestine. The exception is the absorption of vitamin B12 (cobalamin), which is more complicated than the absorption of the other water-soluble vitamins. Absorption of vitamin B12 requires intrinsic factor and occurs in the following steps: (1) Dietary vitamin B12 is released from foods by the digestive action of pepsin in the stomach. (2) Free vitamin B12 binds to R proteins, which are secreted in salivary juices. (3) In the duodenum, pancreatic proteases degrade the R proteins, causing vitamin B12 to be transferred to the intrinsic factor, a glycoprotein secreted by the gastric parietal cells. (4) The vitamin B12 –intrinsic factor complex is resistant to the degradative actions of pancreatic proteases and travels to the ileum, where there is a specific transport mechanism for its absorption. Calcium Most Ca2+ absorption in the gut occurs by passive, unregulated movement through paracellular pathways. Hormonally regulated transepithelial Ca2+ transport takes place in the duodenum. Calcium enters the enterocyte through apical Ca2+ channels and is actively transported across the basolateral membrane by either a Ca2+ -ATPase or by the Na+- Ca2+ antiporter. Calcium absorption is regulated by vitamin D3 Human Physiology: An Integrated Approach 8e Pearson, 2019 Iron Dietary iron is ingested as heme iron in meat and as ionized iron in some plant products. Heme iron is absorbed by an apical transporter on the enterocyte. Ionized iron Fe2+ is actively absorbed by apical cotransport with H+ on a protein called the divalent metal transporter 1 (DMT1). Inside the cell, enzymes convert heme iron to Fe2+ and both pools of ionized iron leave the cell on a transporter called ferroportin. Iron uptake by the body is regulated by a peptide hormone called hepcidin. When body stores of iron are high, the liver secretes hepcidin, which binds to ferroportin. Hepcidin binding causes the enterocyte to destroy the ferroportin transporter, which results in decreased iron uptake across the intestine. Human Physiology: An Integrated Approach 8e Pearson, 2019 Absorption of Water Water is transported through the intestinal membrane entirely by diffusion. Furthermore, this diffusion obeys the usual laws of osmosis. Therefore, when the chyme is dilute enough, water is absorbed through the intestinal mucosa into the blood of the villi almost entirely by osmosis. Conversely, water can also be transported in the opposite direction—from plasma into the chyme. This type of transport occurs especially when hyperosmotic solutions are discharged from the stomach into the duodenum. Within minutes, sufficient water usually will be transferred by osmosis to make the chyme isosmotic with the plasma. Absorption of Electrolytes Enterocytes in the small intestine and colonocytes, the epithelial cells on the luminal surface of the colon, absorb Na+ using three membrane proteins: apical Na+ channels such as ENaC, a Na+-Clsymporter, and the Na+-H+ exchanger (NHE). In the small intestine, a significant fraction of Na+ absorption also takes place through Na+dependent organic solute uptake, such as the SGLT and Na+-amino acid transporters. On the basolateral side of both enterocytes and colonocytes, the primary transporter for Na+ is Na+K+-ATPase. Chloride uptake uses an apical Cl--HCO3exchanger and a basolateral Cl- channel to move across the cells. Potassium and water absorption in the intestine occur primarily by the paracellular pathway. Human Physiology: An Integrated Approach 8e Pearson, 2019 Magnesium absorption Mg2+ is an important intracellular ion that is required as an enzyme cofactor—many enzymes using ATP actually require that the ATP be complexed with Mg2+ —and is critical for neurotransmission and muscular contractions. Mg2+ deficiency can affect neuromuscular, cardiovascular, and gastrointestinal function. Mg2+ is also important for the proper secretion of, and end-organ response to, parathyroid hormone. Thus, Mg2+ depletion is typically associated with hypocalcemia. Mg2+ is widely available in different foods but is present in particularly large amounts in green vegetables, cereals, and meats. Digestion and Absorption in the Large Intestine Numerous bacteria (intestinal flora) inhabiting the colon break down significant amounts of undigested complex carbohydrates and proteins through fermentation. The end products include lactate and short-chain fatty acids, such as butyric acid. Several of these products are lipophilic and can be absorbed by simple diffusion. The fatty acids, for example, are used by colonocytes as their preferred energy substrate. Other substances formed as a result of bacterial activity are vitamin K, vitamin B12, thiamine, riboflavin, and various gases that contribute to flatus in the colon, especially CO2, hydrogen gas, and methane. Vitamin K is required by the liver for normal activation of prothrombin, as well as a few other clotting factors. Therefore, lack of vitamin K or the presence of liver disease that prevents normal prothrombin formation can decrease the prothrombin to such a low level that a bleeding tendency results.