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Digestion and Absorption Tanawat Jirakulaporn Outline • Introduction • Anatomy of GI tract • Digestive enzymes • Secretagogues • • • • Digestion and absorption of protein Digestion and absorption of carbohydrate Digestion and absorption of lipid Bile and bilirubin metabolism Microvilli of Small Intestine Digestion and Absorption • Protein : amino acids, di‐ and tripeptides • Carbohydrate : Monosaccharides • Lipid : Free fatty acids, glycerol and monoglycerides (triglyceride) 2‐monoacylglycerol and 1‐monoacylglycerol (monoglyceride) Digestion and Absorption • Enzymes • Proenzyme Æ active enzyme • Optimal conditions • pH • Cofactors of enzymes, electrolytes (need transporters eg Na+/K+ ATPase), bile (helps to form micelles) Digestion and Absorption • Oral cavity • Mechanical homogenization of food, and mixing food with secretion from salivary glands • Saliva – electrolytes and enzymes (amylase and lingual lipase) • Amylase hydrolyses internal α(1,4) glycosidic linkage of polysaccharides • Lingual lipase hydrolyses triacylglycerol into free fatty acid and diacylglycerol (not effective) Digestion and Absorption • Stomach • Reservoir function • Churning ability – motor function • Secrete enzymes (pepsinogen and gastric lipase from chief cells), HCl and intrinsic factor (from parietal cells), gastrin hormone (mainly from G cells of stomach; little by duodenum and pancreas) Acid Secretion in Stomach (5) Carbonic anhydrase Passive diffusion Acid and Enzyme Secretion in Stomach • 1) HCl is newly synthesized within parietal cells, no storage within the cells • 2) Goblet cells secrete protective mucus with HCO3 layer • 3) Digestive enzymes are in proenzyme isoforms eg. pepsinogen Function of Gastric Acid • Activate pepsinogen to active pepsin and provide optimal pH for pepsin activity (pH 1.8‐3.5) • Denature protein • Kill microorganisms • Help to ionize salts eg calcium, iron Gastrin • Stimulate parietal cells to secrete HCl acid • Stimulate pepsinogen secretion • Increase gastric motility • Peptides, amino acid, high pH – stimulators • Somatostatin, low pH ‐ inhibitors Gastrin ECL = Enterochromaffin‐like cells SST = Somatostatin Zollinger‐Ellison syndrome (gastrinoma) Vitamin B12 absorption Intrinsic factor – parietal cells R‐proteins – Salivary gland Pernicious anemia Gastrectomy, gastric bypass, Ileitis, Crohn’s disease, Achlorhydria Pancreas and Small Intestine Major organs for digestion and absorption Large reserve capacity; pancreatic secretion needs to drop <10% to have maldigestion Final step of carbohydrate and protein digestion occurs at brush border of small intestine by the attached enzymes Lipid digestion is completed by pancreatic lipase at small intestine, not enzymes that attached to the brush border Proenzymes Secretagogues • A substance that stimulates secretion of other substances • Could be neurotransmitters, hormones, pharmacological agents or bacterial toxins Secretagogues Cholecystokinin (CCK) or Pancreozymin • CCK is stimulated by protein and fat entering duodenum • Secreted by small intestine mucosa • Stimulate gall bladder contraction and pancreatic enzyme secretion • Inhibit gastric acid secretion and delay gastric emptying time Secretin • Secreted by duodenal mucosa • Stimulated by acidic pH of food content entering duodenum • Stimulate pancreas to release NaHCO3 to neutralize gastric acid • Coordinate with CCK to stimulate pancreatic enzymes Gut Hormones Digestion and Absorption of Protein Pepsin Activation First 46 amino acids at NH2‐terminus is automatically cleaved when pH<5 (autoactivation) Pepsin can induce autocatalysis Pepsinogen is secreted simultaneously with gastric acid Protein Digestive Enzymes Digestive Enzymes at Brush Border Protein Digestive Enzymes Digestion and Absorption of Protein Intracellular di‐ and tripeptidase Amino acids ‐ Di‐ or tripeptides ‐ Amino acids ‐ Luminal Na+ dependent cotransporter H+ cotransporter Contraluminal Na+ independent transporter Digestion and Absorption of Carbohydrate α‐Amylase Salivary amylase and pancreatic amylase Cleave α(1,4) glycosidic bond Dextrin, maltotriose, maltose, glucose α‐Amylase Digestion and Absorption of Carbohydrate Carbohydrate Digestive Enzymes at Brush Border Digestion and Absorption of Carbohydrate Na+ monosaccharide cotransporter = SGLT1 Æ luminal transporter for Glu and Gal Glucose transporter 5 = GLUT5 Æ luminal transporter for Fructose Glucose transporter 2 = GLUT2 Æ contraluminal transporter for Glu, Gal and Fruc Digestion and Absorption of Lipid • Lipase • Lingual lipase Æ FA + DAG • Gastric lipase Æ FA + DAG • Pancreatic lipase Æ FA + 2‐MAG Æ 2‐MAG can be changed to 1‐MAG Æ 1‐MAG can be cleaved further to glycerol at the lumen or inside intestinal cells • Intestinal lipase Æ cleave 1‐MAG into FA and glycerol (Glycerol in the lumen is absorbed and sent directly into blood stream, but glycerol generated within enterocytes is used in new lipid synthesis) Free fatty acids + 2‐monoglyceride Digestion and Absorption of Lipid Digestion and Absorption of Lipid Digestive polar products form emulsion droplets by mechanical mixing of stomach Pharmacological Agents to Prevent Fat Absorption Fatty acids with sucrose Taste like lipid but can not be hydrolysed Non‐hydrolyzable analog Inhibit pancreatic lipase Bile acids • Bile is a biological detergent • Help digestion and absorption of lipid • Disperse lipid into micelles • Increase transport of free fatty acid and monoglyceride through enterocyte lining • Synthesized by liver and secreted as taurine and glycine conjugates • Reabsorbed at ileum and return to liver with blood circulation and re‐secreted again by liver Bile acids Bile Micelles Critical Micelle Concentration (CMC) = minimal concentration of bile acids to form micelles Thank You!
