1Dr.S. Nayak Digestion Digestion The human diet contains carbohydrates, fat and proteins, which are high molecular weight complex compounds. All have to be digested before get absorbed Digestion of carbohydrates  The major carbohydrates of our diet are starch and glycogen  The polysaccharides are hydrolyzed to simple sugars through the action of number of enzymes. through the action of number of enzymes.  Salivary amylase hydrolyses  -1,4-glycosidic linkages of polysaccharide chain and produce disaccharides and polysaccharide chain and produce disaccharides and monosaccharides. monosaccharides.  The further digestion takes place in the small intestine by the intestinal enzymes, which hydrolyze terminal  -1,4-glycosidic intestinal enzymes, which hydrolyze terminal  -1,4-glycosidic linkage. linkage.

2Dr.S. Nayak Entry of acidic contents of stomach into duodenum, stimulate the mucosal cells to release secretin and cholecystokinin 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 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 Cholecystokinin stimulates the production of digestive enzymes including pancreatic amylase Pancreatic amylase digest the polysaccharides to maltose, isomaltose and a limit dextrin. 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. Disaccharidases such as maltase, lactase and sucrase digest disaccharides like maltose, lactose and sucrose respectively into their respective monosaccharide units.

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5 Cellulose is not digested further because humans does not produce β 1,4-endoglucosidase in digestive juice. Cellulose is not digested further because humans does not produce β 1,4-endoglucosidase in digestive juice. Cellulose helps in easy peristalsis and provides bulk to the feces. Cellulose helps in easy peristalsis and provides bulk to the feces. Lactase deficiency leads to lactose intolerance. Lactase deficiency leads to lactose intolerance. Absorption of monosaccharides The galactose and glucose are absorbed very rapidly by the active process, The galactose and glucose are absorbed very rapidly by the active process, Fructose and mannose are absorbed by a Na + independent facilitative transport mechanism Fructose and mannose are absorbed by a Na + independent facilitative transport mechanism

6Dr.S. Nayak Digestion of proteins In the stomach: The protein does not undergo any digestion in the mouth. The protein does not undergo any digestion in the mouth. When it enters the stomach, it stimulates the secretion of the hormone gastrin, from gastric mucosal cells. When it enters the stomach, it stimulates the secretion of the hormone gastrin, from gastric mucosal cells. The gastrin stimulates the release of gastric juice containing HCl and pepsinogen [rennin in infants]. The 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. The HCl is secreted by parietal cells, which unfolds the proteins and activates the proteolytic enzyme pepsin.

7Dr.S. Nayak Pepsin secreted by chief cells as pepsinogen & converted to pepsin by HCl. This activation is called as zymogen activation Pepsin secreted by chief cells as pepsinogen & converted to pepsin by HCl. This activation is called as zymogen activation Pepsin converts protein polypeptides into tripeptides, dipeptides and amino acids. Pepsin converts protein polypeptides into tripeptides, dipeptides and amino acids. Pepsin specifically hydrolyses the peptide bonds of protein involving the aromatic amino acids (Phenylalanine, tyrosine or tryptophan) or acidic amino acids (aspartic acid and glutamic acid) Pepsin specifically hydrolyses the peptide bonds of protein involving the aromatic amino acids (Phenylalanine, tyrosine or tryptophan) or acidic amino acids (aspartic acid and glutamic acid) Rennin in infants is also called as chymosin or rennet. Rennin in infants is also called as chymosin or rennet. Digestion in the intestine: When the acidic contents from the stomach pass into the intestine, the low pH triggers the secretion of the hormones such as cholecystokinin and secretin. When the acidic contents from the stomach pass into the intestine, the low pH triggers the secretion of the hormones such as cholecystokinin and secretin.

8Dr.S. Nayak Secretin stimulates the release of bicarbonate and pancreatic juice from pancreas into the small intestine Secretin stimulates the release of bicarbonate and pancreatic juice from pancreas into the small intestine Cholecystokinin stimulates the secretion of pancreatic endo and exopeptidases Cholecystokinin stimulates the secretion of pancreatic endo and exopeptidases Endopeptidases cleave internal peptide bonds of proteins to convert into smaller peptides 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) The endopeptidases: trypsin, chymotrypsin, elastase, which are secreted in pro-enzyme forms and are converted to active forms by enteropeptidase (enterokinase)

9Dr.S. Nayak Trypsin hydrolyses peptide bonds whose carboxyl groups are contributed by lysine and arginine 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) 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 non- polar amino acids, such as alanine, serine and glycine Exopeptidases: carboxypeptidase and aminopeptidase Carboxypeptidase is a composition of pancreatic juice and hydrolyses the first peptide bond from the free carboxyl end 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 Aminopeptidase hydrolyses the first peptide bond from the free amino terminal end

10Dr.S. Nayak DIGESTION AND ABSORPTION OF LIPIDS Digestion of lipids depends on the bile salts for the emulsification. Digestion of lipids depends on the bile salts for the emulsification. The heat of the stomach is important in liquefying dietary lipids. The heat of the stomach is important in liquefying dietary lipids. Lipids inhibit gastric motility and so retard the evacuation of the stomach 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 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 In adults no digestion takes place in stomach due to acidic pH The hydrophilic short and medium chain fatty acids are absorbed via stomach wall and enter the portal vein. The hydrophilic short and medium chain fatty acids are absorbed via stomach wall and enter the portal vein. The longer chain fatty acids dissolve in the diet and pass into the duodenum The longer chain fatty acids dissolve in the diet and pass into the duodenum

11Dr.S. Nayak 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 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 This cholecystokinin acts on the gallbladder, causing it to contract to release bile salts into the small intestine This cholecystokinin acts on the gallbladder, causing it to contract to release bile salts into the small intestine Cholecystokinin also acts on the exocrine cells of the pancreas, causing them to release digestive enzymes including lipase Cholecystokinin also acts on the exocrine cells of the pancreas, causing them to release digestive enzymes including lipase The same cholecystokinin also decreases gastric motility, which results in a slow release of the gastric contents into small intestine. The same cholecystokinin also decreases gastric motility, which results in a slow release of the gastric contents into small intestine.

12Dr.S. Nayak The secretin causes the pancreas to release a bicarbonate rich solution which neutralizes the acidic chyme and changes the pH to the alkaline side The secretin causes the pancreas to release a bicarbonate rich solution which neutralizes the acidic chyme and changes the pH to the alkaline side The formation of alkaline pH of the content is very important for the action of lipase and intestinal enzymes The formation of alkaline pH of the content is very important for the action of lipase and intestinal enzymes The bile enters the duodenum and provides the emulsifying action. After emulsification, the lipolytic enzymes such as lipase, phospholipase A2 and cholesterol esterase present in the pancreatic juice hydrolyse lipids. The bile enters the duodenum and provides the emulsifying action. After emulsification, the lipolytic enzymes such as lipase, phospholipase A2 and cholesterol esterase present in the pancreatic juice hydrolyse lipids.

13Dr.S. Nayak Dietary glycerophospholipds are digested by pancreatic phospholipase-A2. This enzyme catalyzing the hydrolysis of fatty acid residues at the 2 nd position of the glycerophospholipid, leaving lysophospholipids Dietary glycerophospholipds are digested by pancreatic phospholipase-A2. This enzyme catalyzing the hydrolysis of fatty acid residues at the 2 nd position of the glycerophospholipid, leaving lysophospholipids This lysophospholipid enter the mucosal cell or degraded further by lysophospholipase enzyme (secreted by intestinal cells) to remove final fatty acid residue This lysophospholipid enter the mucosal cell or degraded further by lysophospholipase enzyme (secreted by intestinal cells) to remove final fatty acid residue Inside the mucosal cells fats are re-synthesized and converted to chylomicron and transported to blood via lymphatic vessel Inside the mucosal cells fats 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. Fatty acids less than 10 carbon atoms along with glycerol are carried by portal blood to the liver.

14Dr.S. Nayak The long chain free fatty acids, free cholesterol, 2- monoglyceride and 1-monoglyceride and lysophospholipid together with bile salts form mixed micelles. The long chain free fatty acids, free cholesterol, 2- monoglyceride and 1-monoglyceride and lysophospholipid together with bile salts form mixed micelles. The 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 re-secretion into the bile. This process is called enterohepatic circulation of bile salts The 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 re-secretion into the bile. This process is called enterohepatic circulation of bile salts The short and medium chain fatty acids are absorbed directly into the intestinal epithelial cells and enters the portal blood to reach the liver The short and medium chain fatty acids are absorbed directly into the intestinal epithelial cells and enters the portal blood to reach the liver

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16Dr.S. Nayak The 1-monoacylglycerol are further hydrolysed in the intestinal mucosal cell by intestinal lipase 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 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 lysophopholipids and cholesterol are also recycled with acyl-CoA to regenerate phopholipids and cholesterol esters. The absorbed lysophopholipids and cholesterol are also recycled with acyl-CoA to regenerate phopholipids and cholesterol esters.

17Dr.S. Nayak 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 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) 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 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 CO 2 and H 2 O with the liberation of large amount of energy. Glycerol is converted to glucose by gluconeogenesis or enters into glycolysis. Fatty acids are oxidized to CO 2 and H 2 O with the liberation of large amount of energy.

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19Dr.S. Nayak Vitamins and Minerals DUODENUM: Fe, Ca, Mg, Zn DUODENUM: Fe, Ca, Mg, Zn JEJUNUM: Vit C, B1 B2, B6, Folic Acid JEJUNUM: Vit C, B1 B2, B6, Folic Acid ILEUM: Fat soluble vitamins are absorbed via micelles; B12 ILEUM: Fat soluble vitamins are absorbed via micelles; B12 COLON: Na; K; vit K from bacterial action COLON: Na; K; vit K from bacterial action ABSORPTION OF MINERALS PHASE 1: INTRALUMINAL Chemical reactions and interactions in the stomach and intestines 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 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 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 Kept available for absorption by ligands such as amino acids, organic acids, sugars

20Dr.S. Nayak PHASE 2: TRANSLOCATION Passage across the membrane into the intestinal mucosal cell Passage across the membrane into the intestinal mucosal cell Small anions: via simple diffusion Small anions: via simple diffusion Cations: facilitated diffusion or active transport. Often more than one mechanism is available depending on concentration of trace element 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 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. 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 Bound forms can be added to the pool or remain bound and are lost via desquamation Reference: Essentials of Biochemistry by Dr S Nayak