1. SSN SBPM Block 5: Digestion & Absorption Overview Carbohydrate digestion and absorption Protein digestion and absorption Fat digestion and absorption Cobalamin (B12) and others Celiac sprue Immunity Shadi (csc43)

2. Overview: Modifications of the gut for digestion and absorption Length Plicae Villi Microvilli (with cores of microfilaments) on surface of ENTEROCYTE Glycocalyx and enzymes and transporters on surface of microvilli

3. Carbohydrate digestion and absorption In lumen Starch  maltose + maltriose + α-limit dextrins Amylase At brush-border Maltose/maltriose  glucose Glucoamylase (maltase) Sucrase-isomaltase α-limit dextrins  glucose Sucrase-isomaltase Sucrose  glucose + fructose Sucrase-isomaltase Lactose  glucose + galactose Lactase SGLT-1 Na + coupled (Na/K ATPase for gradient) D-hexoses w/ pyranose ring apicalbasolateral GLUT-5 Fructose absorption Jejunum Facilitated diffusion GLUT-2

4. Protein digestion and absorption In lumen Protein  AA, di- & tripeptides, & (AA) n via pancreatic PROTEASES Endopeptidases (chymotrypsin, elastin, trypsin) Exopeptidases (carboxypeptidases) Secreted as zymogens by pancreas Activated by TRYPSIN Trypsinogen  trypsin via ENTEROPEPTIDASE (brush border) At brush-border Oligopeptides  AA, di- & tripeptides via PEPTIDASES Also cytoplasmic peptidases Apical AA transporter Na + coupled PepT1 H + /oligopeptide Basolateral AA transporter Na + independent

5. Fat digestion and absorption EMULSION DROPLET  MIXED MICELLE Surface TGs are thinned by digestion by pancreatic lipase & bile salts; replaced by TGs from core of droplet. Lamellae decrease & are ultimately lost. Na+/H+ exchanger creates acidic microenvironment  protonated FFA uncharged (HA)  absorption AND THEN… Glycerol, short- & medium-chain FA pass through straight to capillaries Enterocytes reesterify lipids (long-chain FA, etc) back to TGs & PLs  chylomicrons (packaged in Golgi) secreted into lymphatics TG, DG, CE

6. Cobalamin (B12) Cobalamin (B12) bound to protein in food Stomach: Haptocorrin binds B12 Haptocorrin secreted in stomach by gastric glands Haptocorrin degraded in intestine Small intestine: IF binds B12 IF secreted in stomach by parietal cells Ileum: enterocytes bind IF-B12 complex In ILEUM, by receptor-mediated endocytosis B12 needs to bind transcobalamine II to exit cells

7. Absorption of different nutrients (TESTABLE) Carbohydrates, proteins, lipids: Maximum duodenum Calcium, iron, folate: Active absorption duodenum Bile acids: Maximum ileum Cobalamin (B12): Ileum only

8. Celiac Sprue Duodenum and jejunum Gluten hypersensitivity Defects in fat and protein absorption and lactase deficiency Excessive turnover of gut’s lining  epithelium becomes lined by crypt cells (no enterocyte with brush border enzymes), flat villi  malabsorption Protein malabsorption leads to deficiency in essential AAs  no albumin  low oncotic pressure  edema Fat malabsorption (steatorrhea) leads to fatty stools Lactase deficiency detected by measuring H 2 levels in breath (produced by lactose metabolism by bacteria in colon)

9. Immunity Cf. HISTOLOGY Paneth cells  storage of α-defensins in zymogen granules M cells (overlying Peyer’s patches)  transfer of antigens by transcytosis IgA  secretion by transcytosis into lumen IgA receptor is internalized with IgA, and a part of it becomes secretory component (secreted with IgA)