1. Biochemistry of Digestive Fluids and Enzymes Reference: Ch 25 T. Devlin Textbook of Biochemistry with clinical correlations 7e Mohamad Nusier MD. PhD. 1

2. 2 Secretions of the Gastrointestinal (GI) Tract 1.Primary Organs Salivary Stomach Pancreatic Intestinal 2. 2.Accessory Organs Teeth Tongue Gallbladder Liver

3. 3 FluidVolume(ml/day)pH Saliva1000-12006.0-7.0 Stomach2000-30001.0-3.5 Pancreas1200-20008.0-8.3 Bile secretion 600-7007.8 Brunner’s gland secretion 508.0-8.9 Intestinal juice 2000-30007.8-8.0 Large intestine 607.5-8.0 Daily Secretion of Digestive Fluids

4. 4 Digestive enzymes are classified into four groups: 1. 1.Proteolytic Enzyme: split proteins to amino acids 2. 2.Lipolytic Enzyme: split fats to fatty acids and glycerol 3. 3.Amylolytic Enzyme: split carbohydrate and starch to simple sugars 4. 4.Nucleolytic Enzyme: split nucleic acids to nucleotides

5. 5 Mouth enzymes & Functions 1. Ptyalin: Converts starch to simple soluble sugars 2. Amylase: Converts starch to soluble sugars 3. Betaine: Maintains cell fluid balance as osmolytes 4. Bromelain: Anti-inflammatory agent, tenderizes meat

6. 6 Stomach Enzymes Functions 1. Pepsin: Breaks protein into small peptides ( cuts before Leu, Phe, Trp or Tyr) 2. Gastric amylase: Degradation of starch 3. Gelatinase: Degradation of gelatin and collagen present as proteoglycans in meat 4. Rennin ( Chymosin ): Conversion of liquid milk to solid particles 5. Gastric lipase: Degradation of fat

7. 7 Pancreatic Enzymes & Functions 1. Pancreatic lipase: Degrades triglycerides into fatty acids and glycerol 2. Phospholipase: Hydrolyzes phospholipids into fatty acids and lipophilic substances 3. Trypsin: Converts proteins to basic amino acids 4. Steapsin: Breakdown of triglycerides to glycerol and fatty acids

8. 8 Pancreatic Enzymes & Functions 5. Chymotrypsin: ( cuts after Phe, Trp, or Tyr) Converts proteins to aromatic amino acids 6. Carboxypeptidase: ( cleaves a peptide bond at the C- terminal end of a protein) Degradation of proteins to amino acids 7. Pancreatic amylase: Degradation of carbohydrates to simple sugars 8. Elastases: ( cuts after Ala, Gly, Ser, or Val) Degrade the protein elastin 9. Nucleases: Conversion of nucleic acids to nucleotides and nucleosidespeptide bondprotein

9. 9 Small Intestine Enzymes & Functions 1. Sucrase: Converts sucrose a disaccharides to monosaccharides 2. Maltase: Converts maltose to glucose 3. Lactase: Converts lactose to glucose and galactose 4. Isomaltase: Converts maltose to isomaltose

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12. 12 Digestive Process 1.Ingestion- taking food in Bolus- an amount of food passing through tract 2.Propulsion- moves food through tract Swallowing- voluntary Peristalsis- involuntary muscular waves moves food forward 3.Mechanical digestion- physical chewing, mixing, churning Segmentation- rhythmic local constrictions of intestine for mixing

13. 13 Digestive Process, cont’d 4.Chemical digestion- catabolism/ breakdown of polymers into monomers by enzymes Begins in mouth, essentially complete in small intestine 5.Absorption- passage of digested end products across wall into blood Monomers, vitamins, minerals and water Pass through mucosal cells lining tract Small intestine major absorption site 6.Defecation- eliminates indigestible substances and other wastes from body via anus in form of feces

14. 14 Functions of Saliva 1.Maintenance of oral hygiene Lysozyme, peroxidases (XEROSTOMIA) 2.Maintain mineralization of teeth (Ca 2+ and  pH) 3.Lubrication Speaking and swallowing (mucin) 4.Digestive function Amylase (Ptyalin) & Lipase 5.Solvation Enables one to taste foodstuffs

15. 15 Three Major salivary glands % Total Type 1. Submandibular (submaxillary): 70% sero-mucin 2. Parotid: 25% serous (protein) 3. Sublingual: 5% mucin (mucus) Total volume1,500 mL/day

16. 16 12 3 40 20 40 60 80 100 Ion concentration (mM) Flow rate (mL/min) Na HCO 3 Cl K 20 40 60 80 100 120 140 0 Ion concentration (mM) NaCl HCO 3 K Saliva Plasma Salivary Flow Rate

17. 17 Composition of Human Saliva

18. 18 1.Endocrine cells They are arranged in small islets within the pancreas, secrete directly into the circulation: Insulin Glucagon Somatostatin Polypeptides Pancreatic Structure

19. 19 Pancreatic Structure, Cont’d 2.Exocrine cells They are organized into acini that produce four types of digestive enzymes: Peptidases Lipases Amylases Nucleases

20. 20 Pancreatic Structure, Cont’d 3.Ductal cells Each day they secrete about 1200-1500 mL ofEach day they secrete about 1200-1500 mL of pancreatic juice containing a high concentration of HCO 3 - The HCO 3 - neutralizes gastric acid and regulates the pH of the upper intestine Failure to naturalize the chyme as it enters the intestine will result duodenal ulcers

21. 21 Pancreatic Juice Composition

22. 22 Pancreatic Secretion

23. 23 100 300 500 0 Secretion rate (mL/hr) 0 160 120 80 40 Ion Concentration (mM) 7.8 7.4 8.2 pH 300 260 340 Osmolality Osm pH Na + HCO 3 - Cl - K+K+K+K+ Pancreatic Secretion

24. 24 Functions of Gastric Secretions 1.Digestion of proteins (pepsinogen and HCl) 2.Protection of stomach (HCO 3 - and mucus) 3.Absorption of vitamin B 12 (intrinsic factor) 4.Destroy bacteria and other microorganisms (HCl)

25. 25 Gastric Juice Composition

26. 26 Gastric Secretions

27. 27 1.HCl is secreted into the parietal cell canaliculi by a three step process: Active transport process is begun by transport of K + and Cl - into the canaliculi. C l- is transported by either a pump or through a channel. The flow of Cl- creates a –ve potential inside the canaliculi, causing K+ to flow +vely into the canaliculi H + is exchanged for K + by H + -K + ATPase pump Water enters the canaliculi down the osmotic gradient created by the movement of HCl into the canaliculi HCl Section Mechanism

28. 28 2.The H + entering the canaliculi is supported by dissociation of carbonic acid (H 2 CO 3 ) into H + and bicarbonate (HCO 3 - ) within the parietal cell: H 2 CO 3 is formed from the Rxn catalyzed by carbonic anyhydrase:H 2 CO 3 is formed from the Rxn catalyzed by carbonic anyhydrase: CO 2 + H 2 O → H 2 CO 3 CO 2 + H 2 O → H 2 CO 3 HCO 3 - diffuses back into the plasma in exchange for Cl -HCO 3 - diffuses back into the plasma in exchange for Cl - 3.Most the HCl that is secreted into the stomach is neutralized and reabsorbed within the small intestine HCl Section Mechanism, Cont’d

29. 29 4.Active transport process involve in the generation of HCl, requires a large amount of ATP generated by mitochondria in parietal cell 5.The pH of the parietal cell secretion can be as low as 0.8 6.The H + -K + ATPase pump is irreversibly inhibited by omeprazole (PPI) which is used for the treatment of duodenal and gastric ulcers HCl Section Mechanism, Cont’d

30. 30 1.Cephalic Food in mouth increases secretion of HCl (efferent vagus) Anger and tension increases secretion HCl Fear and depression increases secretion HCl 2.Gastric Stimulated by distension (vago-vagal), hypertonicity Alcohol and AAs (gastrin) Inhibition by H + (-ve feedback, somatostatin) 3.Intestinal Peptides (gastrin), AA’s,) Regulation of Gastric Secretion

31. 31 1.Major digestive organ 2.Longest part of alimentary canal (3-6 hour journey) 3.Three subdivisions Duodenum Shortest but lots going on Hepatopancreatic ampulla- bile duct and main pancreatic duct enter Jejunum Middle portion Ileum Last part joins large intestine at ileocecal valve Small Intestine

32. 32 1.Glands make 1-3 L daily 2.Stimulated by entrance of acidic chime 3.Slightly alkaline to neutralize chyme 4.Largely water with some mucus 5.Relatively enzyme poor because enzymes are bound to the brush border Intestinal Juice

33. 33 Carbohydrate and Protein Digestion

34. 34 Fat and Nucleic Acid Digestion

35. 35 1.Shorter but larger diameter than small intestine 2.Major function in feces elimination and water reabsoprtion 3.12-24 hours Large Intestine

36. 36 1.Most bacteria killed by stomach acid or enzymes 2.Some survive or come up from the anus 3.Ferment indigestible carbohydrates (such as cellulose) 4.Release acids and gases (about 500 mL/day) 5.Also release B complex vitamins and most of the body’s vitamin K need (for clotting) Bacterial Flora

37. 37 Bile Function of Bile Bile is required for the digestion and absorption of fats and for excretion of water-insoluble substances as cholesterol and bilirubinBile is required for the digestion and absorption of fats and for excretion of water-insoluble substances as cholesterol and bilirubin Formation of Bile It is formed from two sites: Hepatocytes Ductal cells

38. 38 Bile, Cont’d Storage of Bile Although it is secreted continuously, but it is stored in the gallbladder during the inter-digestive periodAlthough it is secreted continuously, but it is stored in the gallbladder during the inter-digestive period Release of BileRelease of Bile It is released into the duodenum during the digestive periodIt is released into the duodenum during the digestive period

39. 39 Bile Fluid 1.Flows toward bile duct branches in portal triads 2.Constantly made by hepatocytes 3.List of contents but bile salts and phospholipids important in digestion 4.Bile cholesterol is important because it is one of the few ways in which cholesterol stores can be regulated

40. Bile Salts Role of Bile Salts in Emulsifying Fat 1.Break up large globule into smaller globules 2.Makes for large surface area for lipid digesting enzymes 3.Facilitate fat and cholesterol absorption Most of bile (but not bile salts) will leave with feces Bile salts are actually recycled for reuse

41. 1.The total circulating pool of bile salts is about 3.6 g 2.Because 4-8 g of bile salts are required to digest and absorb a meal (more if the meal is high in fat), the total pool of bile salts must circulate twice during the digestion of each meal 3.The bile salts usually circulate 6-8 times daily` Recycling of Bile Salts