Digestion lect 8.pdf

Digestion Professor Shivananda Nayak The University of the West Indies Faculty of Medical Sciences Department of Preclinical Sciences EWMSC, Mount Hope Trinidad Objectives At the end of this course student should be able to Describe digestion and absorption of the constituents of fats, carbohydrates...

Digestion Professor Shivananda Nayak The University of the West Indies Faculty of Medical Sciences Department of Preclinical Sciences EWMSC, Mount Hope Trinidad Objectives At the end of this course student should be able to Describe digestion and absorption of the constituents of fats, carbohydrates and proteins List the enzymes of gastrointestinal tract Dr.S. Nayak 2 Digestion    Diet contains carbohydrates, fat and proteins They are high molecular weight complex compounds. Must be digested for absorption Digestion of carbohydrates The major carbohydrates of our diet are Polysaccharides (starch and glycogen) Hydrolyzed to simple sugars through enzymes. Salivary amylase hydrolyses -1,4-glycosidic linkages of polysaccharide chain to produce mono and disaccharides. Further digestion happens in the small intestine by the intestinal enzymes (which hydrolyze terminal -1,4-glycosidic linkage). Dr.S. Nayak 3 Entry of acidic contents of stomach into duodenum, stimulate the mucosal cells to release secretin and cholecystokinin Secretin stimulates the pancreas to release bicarbonate and water to neutralize the acidic chyme from the stomach Cholecystokinin stimulates the production of digestive enzymes including pancreatic amylase Pancreatic amylase digest the polysaccharides to maltose, isomaltose and a limit dextrin. Disaccharidases such as maltase, lactase and sucrase digest disaccharides like maltose, lactose and sucrose respectively into their respective monosaccharide units. Dr.S. Nayak 4 Dr.S. Nayak 5 Dr.S. Nayak 6 Humans does not produce β 1,4-endoglucosidase in digestive juice to digest cellulose. Cellulose helps in easy peristalsis and provides bulk to the feces. Lactase deficiency leads to lactose intolerance. Absorption of monosaccharides The galactose and glucose are absorbed very rapidly by the active process Fructose and mannose are absorbed by a Na+ independent facilitative transport mechanism Dr.S. Nayak 7 Dr.S. Nayak 8 Digestion of proteins Stomach: Protein does not undergo digestion in the mouth. Enters the stomach and stimulates the secretion of the hormone gastrin (from gastric mucosal cells). Gastrin stimulates the release of gastric juice containing HCl and pepsinogen [rennin in infants]. The HCl is secreted by parietal cells, which unfolds the proteins and activates the proteolytic enzyme pepsin. Dr.S. Nayak 9 Pepsin secreted by chief cells as pepsinogen & converted to pepsin by HCl (zymogen activation). Pepsin digests protein polypeptides into tripeptides, dipeptides and amino acids. Pepsin specifically hydrolyses the peptide bonds of protein involving the aromatic amino acids or acidic amino acids Rennin in infants is also called as chymosin or rennet. Intestine: Entry of acidic contents from the stomach into the intestine triggers the secretion of the hormones such as cholecystokinin and secretin. Dr.S. Nayak 10 Secretin stimulates the release of bicarbonate and pancreatic juice from pancreas into the small intestine Cholecystokinin stimulates the secretion of pancreatic endo and exopeptidases Endopeptidases cleave internal peptide bonds of proteins to convert into smaller peptides The endopeptidases: trypsin, chymotrypsin, elastase, which are secreted in pro-enzyme forms and are converted to active forms by enteropeptidase (enterokinase) Dr.S. Nayak 11 Trypsin hydrolyses peptide bonds whose carboxyl groups are contributed by lysine and arginine Chymotrypsin specifically hydrolyses the peptide bonds involving the carboxyl group aromatic amino acids (Phenylalanine, tyrosine or tryptophan). It also splits peptide bonds of leucine, methionine asparagine and histidine Elastase hydrolyses those peptide bonds formed by nonpolar amino acids, such as alanine, serine and glycine Dr.S. Nayak 12 Exopeptidases: Carboxypeptidase and Aminopeptidase Carboxypeptidase is a composition of pancreatic juice and hydrolyses the first peptide bond from the free carboxyl end Aminopeptidase hydrolyses the first peptide bond from the free amino terminal end Absorption The absorption of amino acids includes Na+ dependent active transport mechanism, which requires ATP as energy source. Dr.S. Nayak 13 DIGESTION AND ABSORPTION OF LIPIDS Digestion of lipids depends on the bile salts for the emulsification. Lipids inhibit gastric motility and so retard the evacuation of the stomach The gastric lipase and lingual lipase of chyme are active only at neutral pH In adults no digestion takes place in stomach due to acidic pH Dr.S. Nayak 14 The hydrophilic short and medium chain fatty acids are absorbed via mucosal cell and enter the portal vein. The longer chain fatty acids dissolve in the diet and pass into the duodenum Entry of acidic chyme from the stomach into the duodenum stimulates the secretion of enteric hormones like secretin and cholecystokinin by the mucosal cells of duodenum Cholecystokinin a) Helps in the contraction of gallbladder to release bile salts into the small intestine b) Acts on the exocrine cells of the pancreas, causing them to release digestive enzymes including lipase c) Decreases gastric motility, which results in a slow release of the gastric contents into small intestine. Dr.S. Nayak 16 Secretin causes the pancreas to release a bicarbonate rich solution which neutralizes the acidic chyme and changes the pH to the alkaline side Formation of alkaline pH of the content is very important for the action of lipase and intestinal enzymes Bile enters the duodenum and provides the emulsifying action. After emulsification, the lipolytic enzymes such as lipase, phospholipase A2 and cholesterol esterase of pancreatic juice hydrolyse lipids. Dr.S. Nayak 17 Dietary glycerophospholipds are digested by pancreatic phospholipase-A2 (hydrolysis of fatty acid residues at the 2nd position of the glycerophospholipid to form lysophospholipid). Inside the mucosal cells fats (TG) are re-synthesized and converted to chylomicron and transported to blood via lymphatic vessel Fatty acids less than 10 carbon atoms along with glycerol are carried by portal blood to the liver. Dr.S. Nayak 18 Dr.S. Nayak 19 Long chain free fatty acids, free cholesterol, 2monoglyceride and 1-monoglyceride and lysophospholipid together with bile salts form mixed micelles. Bile salts aggregate with their hydrophobic region placed internally and hydrophilic region facing the water medium and makes the micelle water soluble. The glycerides and long chain fatty acids in these micelles are transported into the intestinal mucosal cells leaving bile salts in the medium itself. The bile salts are reabsorbed in the intestine and returned to the liver by the portal vein for resecretion into the bile. This process is called enterohepatic circulation of bile salts Dr.S. Nayak 20 Dr.S. Nayak 21 The 1-monoacylglycerol are further hydrolysed in the intestinal mucosal cell by intestinal lipase The 2-monoacylglycerol are reconverted to triglyceride. The utilization of fatty acids inside the mucosal cell for the re-synthesis of triacylglycerol needs the activation to acyl-CoA by thiokinase enzyme The absorbed lysophospholipids and cholesterol are also recycled with acyl-CoA to regenerate phospholipids and cholesterol esters. Dr.S. Nayak 22 The triacylglycerol, phospholipid, cholesterol ester synthesized in the intestinal mucosal cell and the absorbed fat soluble vitamins are transported from the mucosal cells into the lymph in the form of chylomicron The absorbed lipids are either oxidized mainly in the liver or stored in the depots (adipose tissue) For utilization by the body, triglycerides are first hydrolysed by lipase to release glycerol and free fatty acids Glycerol is converted to glucose by gluconeogenesis or enters into glycolysis. Fatty acids are oxidized to CO2 and H2O with the liberation of large amount of energy. Dr.S. Nayak 23 Vitamins and Minerals DUODENUM: Fe, Ca, Mg, Zn JEJUNUM: Vit C, B1 B2, B6, Folic Acid ILEUM: Fat soluble vitamins are absorbed via micelles; B12 COLON: Na; K; vit K from bacterial action ABSORPTION OF MINERALS PHASE 1: INTRALUMINAL Chemical reactions and interactions in the stomach and intestines Cations (eg. Ca 2+): influenced by pH of luminal contents and composition of chyme from stomach Soluble in acid pH of stomach but form insoluble hydroxides in the higher pH of the small intestine Kept available for absorption by ligands such as amino acids, organic acids, sugars Dr.S. Nayak 24 PHASE 2: TRANSLOCATION Passage across the membrane into the intestinal mucosal cell Small anions: via simple diffusion Cations: facilitated diffusion or active transport. Often more than one mechanism is available depending on concentration of trace element PHASE 3: MOBILIZATION Transport across the serosal surfaces of cell into blood or Sequestered within the cell or BOTH Fe and Zn are either bound to proteins within the cell or added to the intracellular pool. Bound forms can be added to the pool or remain bound and are lost via desquamation Reference: Essentials of Biochemistry by Dr S Nayak Dr.S. Nayak 25