1 Biochemistry Ammar Madkhana 16/11/2015 DR. Mohammad Nuseir 1 P a g e
Biochemistry of Digestive Fluids and Enzymes **************************************** 1) Secretions of the GIT: -All secretions of GIT come from either: Primary or Accesory Organs. Primary Organs Salivary Glands Stomach Pancreas Intestinal Accesory Organs Teeth (mechanical chewing) Tongue Gallbladder Liver 2) Daily Secretions Of Digestive Fluids: Fluid Volume (ml/day) PH Saliva 1000-1200 6 7 Stomach 2000-3000 1 3.5 (acidic) to enzymes work Pancreas 1200-2000 8 8.3 Bile secretion 600-700 7.8 Burnner s Gland secretion 50 8 8.9 Intestinal Juice 2000-3000 7.8 8 (alkaline) Large Intestine 60 7.5 8 -Digestive enzymes are classified into 4 groups: 1) Proteolytic Enzyme:split proteins smaller peptides +amino acids. 2) Lipolytic Enzyme: split fats into (fatty acids and glycerol). 3) Amylolytic Enzyme: split carbohydrate & starch simple sugars. 4) Nucleolytic Enzyme: split nucleic acids nucleotides +nucleosides. Note:These enzymes split moleucles to smaller one for easier absorption 2 P a g e
1) Mouth Enzymes & Functions: Enzyme: Function: Ptyalin Converts Starch to simple soluble sugar Amylase Converts Starch to soluble sugars Betaine Maintains cell fluid balance as Osmolytes Bromelain Anti-inflammatory agent, tenderizes meat. 2) Stomach Enzymes & Functions : Enzyme: Function: Pepsin: Breaks protein into small peptids Gastric amylase Degradation of Starch Gelatinase Degradation of Gelatin and collagen present as Proteoglycans in meat. Renin (Chymosin) Conversion of Liquid milk to solid Particls. it is specific for neonates. Gastric Lipase Degradation of Fat 3) Pancreatic Enzymes & Functions : Enzyme: Function: Pancreatic Lipase Degrades Triglyceride into: fatty acids and Glycerol Phospholipase Hydrolyzes phospholipids into : fatty acids and lipophilic substances Trypsin Converts proteins to basic amino acids Steapsin Breakdown of triglycerides into: Glycerol and fatty acids Chymotrypsin Converts proteins to aromatic amino acids it cuts at a site after (Phe, Trp or Tyr) Carboxypeptidase Degradation of proteins into amino acids Pancreatic amylase Degradation of Carbohydrates into simple sugars Elastases Degradation of the protein : Elastin. Nucleases Conversion of Nucleic acids into: Nucleotides and Nucleosides. 3 P a g e
Notes: 1) Pepsin breaks protein at a site before Leu, Phe, Trp, Tyr (these amino acids have bulky side chains which are recognized by pepsin). 2) Carboxypeptidase enzyme has several types ( A, b,others) and it cleaves a peptide bond at the C-terminal end of a protein. 3) Elastase enzyme cuts the protein elastin after small aliphatic amino acids like: Ala,Gly, Ser or Val (have small side chain). 4) The difference between Nucleotides and Nucleosides is : Phsophate group where : nucleotides have Phosphate group but Nucleosides don t. Enzyme: Sucrase Maltase Lactase IsoMaltase Small Intestine Enzymes & Functions Function: Converts Sucrose ( Disaccharides) to Monosaccharides. Converts Maltose (2 glucose) to Glucose Converts Lactose to Glucose and Galactose Converts Maltose Isomaltos Note: These enzymes act on disaccharides and convert them into Monosaccharides. Digestive Process **************** -Digestive process is composed of 6 Phases: 1) Ingestion: mean taking food into mouth and forming the bolus. so bolus mean : amount of food passing through tract. 2) Propulsion: mean the movement of food through Tract. it is divided into : Swallowing (Voluntary) & Perstalasis ( Involuntary). 4 P a g e
3) Mechanical Digestion: mean Physical chewing, mixing, churning. Segmentation : rhythemic Local constrictions of intestine for mixing. 4) Chemical Digestion: Catabolism or breakdown of polymers into monomers by enzymes it begins in mouth but essentially complete in small intestine. 5) Absorption: mean Passage of digested end products across wall into blood So monomers, vitamines, minerals and water pass through mucosal cells lining tract. Note: The major absorption site is SMALL INTESTINE. 6) Defecation: mean Eliminating indigestable substances and other wastes from body via Anus in form of feces. Saliva : Functions & Types *************************** 1) Functions of Saliva: a) Maintenance of Oral Hygiene by : Lysozyme and peroxidase (XEROSTOMIA= Dryness of the mouth). b) Maintenance of Mineralization of Teeth by : Ca +2 and high Ph. c) Lubrication by mucin for speaking and swallowing. d) Digestive Function by Amylase (Ptyalin) & Lipase. e) Solvation: mean Enables one to taste foodstuffs. 2) Types of Salivary glands: Saliva is secreted from 3 major salivary glands: Type Submandibular (Submaxillary) Parotid Sublingual % of total Salivary Secretion 70 % serous (mucin) 25 % serous (protein) 5 % Mucus (Mucin) 5 P a g e
3) Salivary Flow Rate: From the figure above we have to know : the concentration of ions differ between the plasma and the saliva where the concentration of Sodium and chloride ions (Na + & Cl - ) in plasme are much more than saliva but the Bicarbonate and Potassium ions (HCO 3 - & K + ) are the Same in saliva and plasma. ********************************************************* Pancreatic Structure ******************** 1) Endocrine Cells: -They are arranged in small islets within the pancrease These cells secrete Directly into the Circulation the following : a) Insuline & Glucagon : which regulate the glucose level in the blood. b) Somatostatin. c) Polypeptides. 6 P a g e
2) Exocrine Cells: -They are oraganized into acini that produce 4 types of Digestive enzymes: a) Peptidases. b) Lipases. c) Amylases. d) Nucleases. which all have a role in digestion. 3) Ductal Cells: (secrete mainly Bicarbonate HCO 3 - ) -Each day They secrete about 1200-1500 ml of Pancreatic Juice containing a High Concentration of HCO 3 -. This HCO 3 - neutralizes gastric acid and regulates the PH of the upper intestine when it fails to neutralize the Chyme when it enters the intestine this will result Deudonal Ulcer. Pancreatic Secretion ********************* This figure shows How the Ductule cells secrete the HCO 3 -? It does that by a process of formation of Carbonic acid H 2 CO 3 from the union of CO 2 + H 2 O by the help of enzyme called: Carbonic Anhydrase then this H 2 CO 3 will dissociate to give Proton H + and bicarbonate HCO3 -. Which will directly be secreted to the lumen but 7 P a g e
the the proton H + will help in the transportation of Sodium from blood to the lumen. -After the pancreatic Secretion : PH will increase in the lumen of intestine because the HCO 3 - is increased and Cl - is decreased. Functions Of Gastric Secretions: 1) Digestion of Proteins by pepsin enzyme that is produced by the activation of Pepsinogen by HCL so (Pepsinogen + HCL Pepsin). 2) HCO 3 - and Mucus Protects the stomach from digest itself by its own enzymes and the acidic HCL. 3) Absorption of Vitamin B12 by Intrinsic Factor. 4) Destroy bacteria and Other Microorganisms by: HCL. HCL Secretion Mechanism ************************* 1) HCl is secreted into the parietal cell canaliculi by 3 step process: a) Active transport process is begun by transport of K + and Cl - into the canaliculi where Cl - is transported by either a pump or through channel. The flow of Cl - creates ( vely) potential inside the canaliculi causing K + to flow (+vely) into the canaliculi. b) H + is exchanged for K + by H + -K + ATPase pump. c) Water enters the canaliculi down the osmotic gradient created by the movement of HCl into the canaliculi. ------------------------------------------------------------------------------------- 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. 8 P a g e
H 2 CO 3 is formed from the Reaction that catalyzed by carbonic anyhydrase: CO 2 + H 2 O H 2 CO 3 then HCO 3 - diffuses back into the plasma in exchange for Cl -. Notes: 1) Most the HCl that is secreted into the stomach is neutralized and reabsorbed within the small intestine. 2) Active transport process involve in the generation of HCl requires a large amount of ATP generated by the mitochondria in parietal cell. 3) The ph of the parietal cell secretion can be as low as 0.8. 4) The H + -K + ATPase pump is irreversibly inhibited by omeprazole (PPI) which is used for the treatment of duodenal and gastric ulcers. Regulation of Gastric Secretion ***************************** 1) Cephalic: (involve central nervous system) -Food in mouth increases secretion of HCl (efferent vagus). - Anger and tension also increases the secretion of HCl. - Fear and depression also increases the secretion of HCl. 2) Gastric: - Stimulated by distension (vago-vagal) and hypertonicity. -Alcohol and Amino acids increases the acidity (by Gastrin) and Inhibition by H + (-ve feedback or somatostatin). 3) Intestinal: -Peptides (Gastrin), Amino acids and fats increase the secretion of HCL. 9 P a g e
Small Intestine ***************** -it is the Major digestive organ and the longest part of alimentary canal (3-6 hour journey mean the food takes this time to get out from it). -it is divided into 3 subdivisions: 1) Deudenum: is the shortest but lots things going on here like: a)secretion of the pancreatic enzyme from main pancreatic duct where The Hepatopancreatic ampulla-bile duct and main pancreatic duct open and enter the deudenum. b) Neutralization of the acidity that come from the stomach. 2) Jejunum: is the middle portion. 3) Ileum: is the Largest part of the small intestine and the last part joins the large intestine at ileocecal Valve. Intestinal Juice ***************** -It is the juice that is secreted from The glands where they secret about 1-3 liters daily the secretory glands is stimulated by enterance of acidic Chyme. Important note: The intestinal juice is slightly alkaline by the action of Bicarbonate HCO 3 - to neutralize chyme and it contains largely water and some mucus and it is poor in enzymes because enzymes are bound to the brush border. 10 P a g e
Carbohydrate and Protein Digestion ********************************* DR focus on the pepsin and Amylase only so don t worry about this figure. Fat and Nucleic acid Digestion *************************** 11 P a g e dr focus on Emulsification of fats only.
Large Intestine *************** -It is shorter than small intestine but large diameter. -The major fanction of Large intestine is : Feces elimination and water reabsorption. -it takse about 12-24 HOURS journey (mean the food take this time to get out from the large intestine) Bacterial Flora *************** -Most bacteria killed by stomach acid or enzymes but some survive or come up from the anus. -These bacterial flora ferment indigestible Carbohydrates(like Cellulose) and They release the following : 1) Acids and gases (about 500 ml/day). 2) B complex vitamin. 3) most of the body s vitamin K need (we need it for blood clotting). ******************************************************** The Bile *********** -The function of the Bile is : digestion and absorption of fats and for excretion of water-insoluble substances as cholesterol and bilirubin. -The formation of The bile : it is formed from 2 sites: Hepatocytes & Ductal cells. (in general biochem we take how is formed in details by conjugation of bilirubin directly or indirectly). -The Storage of Bile: Although it is secreted continuously but it is stored in the Gallbladder during the inter-digestive period. - It is released into the duodenum during the digestive period. 12 P a g e
The Bile Fluid: is constantly made by hepatocytes and flows toward bile duct branches in portal triads. this fliud contains lists of contents but the most important contents are : Bile salts and phospholipids.(important in digestion) Note: Bile cholesterol is important because it is one of the few ways in which cholesterol stores can be regulated. Bile salts: have role in emulsifying Fat where they : 1) Breakup large globule into smaller globules. 2) increases the large surface area for lipid digesting enzymes. 3) Facilitate fat and cholesterol absorption. Most of the bile (but not bile salts) will leave with feces. Bile salts are actually Recycled and reused but How much? -The total circulating pool of bile salts is about 3.6 g but we need 4-8 g of bile salts to digest and absorb a meal (need more if the meal is high in fat) so the total pool of bile salts must circulate twice during the digestion of each meal The bile salts usually circulate 6-8 times daily. The End Good luck ALL ^^ Done by: Ammar Madkhana 13 P a g e
Summary *********** -Primary Organs = Salivary, Stomach, Pancreatic, Intestinal. -Accesory Organs = Teeth, Tongue, Gallbladder, Liver. -The media of The Stomach is : Acidic (PH = 1 3.5) While the media of Small intestine is : Alkaline (PH=7.8 8). -The volume of Salive that is secreted per day = 1000-1200 ml (1-1.2 L) -Digestive Enzymes are : 1) Proteolytic (proteins amino acids) 2) Lipolytic (Fats fatty acids + Glycerol) 3) Amylolytic (Carbohydrate simple sugars) 4) Nucleolytic (nucleic acids nucleotides) 1) Mouth Enzymes & Functions: Enzyme: Function: Ptyalin + Amylase Converts Starch to simple soluble sugar Betaine Maintains cell fluid balance as Osmolytes Bromelain Anti-inflammatory agent, tenderizes meat. 2) Stomach Enzymes & Functions : Enzyme: Function: Pepsin: Breaks protein small peptids Gastric amylase Degradation of Starch Gelatinase Degradation of Gelatin and collagen present as Proteoglycans in meat. Renin (Chymosin) Conversion of Liquid milk to solid Particls. Gastric Lipase Degradation of Fat 3) Pancreatic Enzymes & Functions : Enzyme: Function: Pancreatic Lipase Degrades Triglyceride into: fatty acids and Glycerol Phospholipase Hydrolyzes phospholipids into : fatty acids and lipophilic substances 14 P a g e
Trypsin Converts proteins basic amino acids Steapsin Breakdown of triglycerides into: Glycerol and fatty acids Chymotrypsin Converts proteins aromatic amino acids Carboxypeptidase Degradation of proteins amino acids Pancreatic amylase Degradation of Carbohydrates simple sugars Elastases Degradation of the protein : Elastin. Nucleases Conversion of Nucleic acids into: Nucleotides and Nucleosides. Small Intestine Enzymes & Functions Enzyme: Function: Sucrase Converts Sucrose ( Disaccharides) to Monosaccharides. Maltase Converts Maltose to Glucose Lactase Converts Lactose to Glucose and Galactose IsoMaltase Converts Maltose Isomaltos -Digestive process is 6 phases : Ingestion + Propulsion + Mechanical Digestion + Chemical digestion + absorption + Defecation. -The Bolus mean amount of food passing through tract. -Propulsion = Swallowing (Voluntary) + Perstalasis ( Involuntary). -Chemical digestion begins in mouth but complete in small intestine. - The major absorption site is SMALL INTESTINE. Functions of Saliva= Hygiene + Mineralization of teeth (Ca +2 + high Ph) + Lubrication + digestive(amylase+lipase) + Solvation. Type Submandibular (Submaxillary) Parotid Sublingual % of total Salivary Secretion 70 % serous (mucin) 25 % serous (protein) 5 % Mucus (Mucin) 15 P a g e
Pancreatic secretion: -From Endocrine cells:insuline+glucagon +somatostatine+ Polypeptides. -From Exocrine cell : Peptidases +Lipases +Amylases + Nucleases. -From Ductal Cells : Pancreatic Juice(High Concentration of HCO 3 - ). The ph of the parietal cell secretion can be as low as 0.8. Functions of Gastric Secretion : Digestion of proteins by pepsine and protection of Stomch from digest itself + Absorption of Vitamin B12 by intrinsic factor + Dystroy bacteria by HCL. -HCl is secreted into the parietal cell canaliculi by 3 step process: Active transport + H + is exchanged for K + + Water enters. H 2 CO 3 is formed by : carbonic anyhydrase (CO 2 + H 2 O H 2 CO 3 ) -The H + -K + ATPase pump is irreversibly inhibited by omeprazole Regulation Of Gastric Secretion :1) Cephalic (increases secretion HCl) 2) Gastric & 3) Intestinal. -The longest part of alimentary canal is : Small Intestine. -Intestinal Juice = 1-3 liters daily. -The intestinal juice is slightly alkaline. -The major fanction of Large intestine is : Feces elimination and water reabsorption. -Bacterial Flora secrete: Acids+gases+Vitamin B complex+vitamin K. - The function of the Bile is : digestion and absorption of fats. -The formation of The bile from 2 sites: Hepatocytes & Ductal cells. -The Storage of Bile is in : Gallbladder. -Bile salts: have role in emulsifying Fat. - Most of the bile (but not bile salts) will leave with feces. 16 P a g e