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Biochemistry of Digestive Fluids and Enzymes Reference: Ch 25 T. Devlin Textbook of Biochemistry with clinical correlations 7e Mohamad Nusier MD. PhD. 1 Secretions of the Gastrointestinal (GI) Tract 1. Primary Organs • Salivary • Stomach • Pancreatic • Intestinal 2. Accessory Organs • Teeth • Tongue • Gallbladder • Liver 2 Daily Secretion of Digestive Fluids Fluid Volume (ml/day) pH Saliva Stomach 1000-1200 2000-3000 6.0-7.0 1.0-3.5 Pancreas 1200-2000 8.0-8.3 600-700 7.8 50 2000-3000 8.0-8.9 7.8-8.0 60 7.5-8.0 Bile secretion Brunner’s gland secretion Intestinal juice Large intestine 3 Digestive enzymes are classified into four groups: 1. Proteolytic Enzyme: split proteins to amino acids 2. Lipolytic Enzyme: split fats to fatty acids and glycerol 3. Amylolytic Enzyme: split carbohydrate and starch to simple sugars 4. Nucleolytic Enzyme: split nucleic acids to nucleotides 4 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 5 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): milk to solid particles 5. Gastric lipase: Conversion of liquid Degradation of fat 6 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 7 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 Cterminal 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 8 nucleosides 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 9 10 11 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 12 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 13 Functions of Saliva 1. Maintenance of oral hygiene • Lysozyme, peroxidases (XEROSTOMIA) 2. Maintain mineralization of teeth • (Ca and pH) 2+ 3. Lubrication • Speaking and swallowing (mucin) 4. Digestive function • Amylase (Ptyalin) & Lipase 5. Solvation • Enables one to taste foodstuffs 14 Three Major salivary glands % Total Type 1. Submandibular (submaxillary): 70% sero-mucin 2. Parotid: 25% serous (protein) 3. Sublingual: 5% mucin (mucus) Total volume 1,500 mL/day 15 Salivary Flow Rate Na Cl 100 Na 80 80 60 60 40 HCO3 Cl 20 HCO3 K K 0 1 2 3 Flow rate (mL/min) 40 20 0 4 Plasma 16 Saliva Ion concentration (mM) 120 100 Ion concentration (mM) 140 Composition of Human Saliva 17 Pancreatic Structure 1. Endocrine cells • They are arranged in small islets within the pancreas, secrete directly into the circulation: • • • • Insulin Glucagon Somatostatin Polypeptides 18 Pancreatic Structure, Cont’d 2. Exocrine cells • They are organized into acini that produce four types of digestive enzymes: • • • • Peptidases Lipases Amylases Nucleases 19 Pancreatic Structure, Cont’d 3. Ductal cells • Each day they secrete about 1200-1500 mL of pancreatic juice containing a high concentration of HCO3 • The HCO3 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 20 Pancreatic Juice Composition 21 Pancreatic Secretion 22 Ion Concentration (mM) pH 8.2 340 pH 7.8 Osm 300 7.4 260 160 Osmolality Pancreatic Secretion + Na HCO3- 120 80 ClK+ 40 0 0 300 100 Secretion rate (mL/hr) 500 23 Functions of Gastric Secretions 1. Digestion of proteins (pepsinogen and HCl) 2. Protection of stomach (HCO3 and mucus) 3. Absorption of vitamin B12 (intrinsic factor) 4. Destroy bacteria and other microorganisms (HCl) 24 Gastric Juice Composition 25 Gastric Secretions 26 HCl Section Mechanism 1. HCl is secreted into the parietal cell canaliculi by a three step process: • Active transport process is begun by transport of + lK and Cl into the canaliculi. C 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 27 canaliculi HCl Section Mechanism, Cont’d + 2. The H entering the canaliculi is supported by dissociation of carbonic acid (H2CO3) into H+ and bicarbonate (HCO3 ) within the parietal cell: • • • H2CO3 is formed from the Rxn catalyzed by carbonic anyhydrase: CO2 + H2O → H2CO3 HCO3 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 28 HCl Section Mechanism, Cont’d 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 29 Regulation of Gastric Secretion 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,) 30 Small Intestine 1. Major digestive organ 2. Longest part of alimentary canal (3-6 hour journey) 3. Three subdivisions • Duodenum • • • Jejunum • • Shortest but lots going on Hepatopancreatic ampulla- bile duct and main pancreatic duct enter Middle portion Ileum • Last part joins large intestine at ileocecal valve 31 Intestinal Juice 1. 2. 3. 4. 5. Glands make 1-3 L daily Stimulated by entrance of acidic chime Slightly alkaline to neutralize chyme Largely water with some mucus Relatively enzyme poor because enzymes are bound to the brush border 32 Carbohydrate and Protein Digestion 33 Fat and Nucleic Acid Digestion 34 Large Intestine 1. Shorter but larger diameter than small intestine 2. Major function in feces elimination and water reabsoprtion 3. 12-24 hours 35 Bacterial Flora 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) 36 Bile • Function of Bile • Bile 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 37 Bile, Cont’d • Storage of Bile • Although it is secreted continuously, but it is stored in the gallbladder during the inter-digestive period • Release of Bile • It is released into the duodenum during the digestive period 38 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 39 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 Recycling of Bile Salts 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`