Lipid Metabolism (HMC 2024) PDF

Metabolism of Lipids  Dr. Dehab Belay HMC 2024  Digestion and absorption of lipids Major dietary lipids are Triacylglycerol – 90-95 % Cholesterol ester/cholesterol Phospholipids  Types and Functions of lipids 1)...

Metabolism of Lipids  Dr. Dehab Belay HMC 2024  Digestion and absorption of lipids Major dietary lipids are Triacylglycerol – 90-95 % Cholesterol ester/cholesterol Phospholipids  Types and Functions of lipids 1) Triacylglycerols (TAG) – energy storage, insulation 2) Glycerophospholipids (PL) – bilayer formation, signaling 3) Sphingolipids – bilayer formation, signalling 4) Fatty Acids (FA) – signalling. These are also covalently linked to “backbones” (e.g., glycerol for 1 & 2) to form (1)–(3) above 5) Steroids – signalling, modification of bilayer thickness and fluidity, and steroid hormones Digestion of Triacylglycerols  Steps of Lipid Digestion A. Processing of dietary lipid in the stomach B. Emulsification of dietary lipid in the small intestine C. Degradation of dietary lipids by pancreatic enzymes Digestion of lipids Digestion in mouth  There is hardly any digestion of fats in the mouth-even though lingual lipase is available.  Is secreted from Ebner's glands of the tongue  Its pH optima is on the acidic side, therefore, digestion its activity is mainly in the stomach Digestion in the stomach  Works mainly in the stomach, particularly within the core of food bolus to hydrolyze short-chain fatty acids at C1/C3 of glycerol.  Therefore, gastric lipase is able to digest the fats in cow's milk, butter, ghee and coconut oil.  The released water-soluble fatty acids are absorbed from stomach wall to the portal circulation.  Gastric lipase may hydrolyze 30% of dietary triacylglycerols.  Gastric lipase  Gastric lipase is secreted by the chief cells in response to gastrin.  It has a wide pH range near neutrality and requires calcium for activation.  It cannot work without emulsification of fat and within the acidic pH of the stomach.  Gastric lipase has an important role in the milk fat digestion in the stomach of infants since the pH of stomach in infants is not as acidic as in adults.  The presence of fat in stomach stimulates secretion of enterogasterone hormone, which delays the gastric emptying time of food.  The longer stay of food in the stomach gives the characteristic high satiety value.  Digestion in small Intestine  Digestion of lipids begins in the duodenum, when the entrance of the acid chyme from the stomach stimulates the secretion of enteric hormones (small peptides) by the duodenal mucosa.  Gastric HCl stimulates the secretion of secretin that promotes the release of HCO 3--rich juice from the pancreas into the duodenum via the pancreatic duct.  Presence of fat in small intestine stimulate the release of cholecystokinin from intestinal mucosa to the blood to induce the release of zymogen granules from the pancreas and the contraction of the gall bladder to release of bile.  Pancreatic enzymes The pH of the intestine rises to alkaline side due to the presence of bicarbonate in the pancreatic juice. Three lipid-specific proenzymes are activated by the bile acids and the neutral pH. These enzymes are:  Pancreatic lipase, also known as Steapsin  Phospholipase A2  Cholesterol esterase  Colipase (secreted as Procolipase-helps to anchor and stabilize pancreatic lipase) Pancreatic lipase Pancreatic lipase, also known as Steapsin, cleaves triacylglycerols to 2- monoacylglycerol and two free fatty acids. It has an optimum pH of 6.0 that is furnished by the co-secreted pancreatic bicarbonate. Pancreatic lipase O CH2 O C CH2 R1 CH2 OH O O O O Pancreatic lipase R2 CH2 C O CH R2 CH2 C O CH + HO C CH2 R1 + HO C CH2 R3 O 2H2O Free fatty acid Free fatty acid CH2 O C CH2 R3 CH2 OH A triglyceride (Triacylglycerol) 2-monoacylglycerol Phospholipase A2  Phospholipase A2 is secreted as proenzyme from the pancreas that is activated by trypsin.  It hydrolyzes fatty acid at C2 of glycerophospholipids. Other intestinal phospholipases and phosphatases complete the hydrolysis of phospholipids into glycerol, free fatty acids, choline and phosphate. But the main product is the lysophospholipids. Phospholipids + H2O  Lysophospholipids + free fatty acids  The site of action of different phospholipids is next slide. Phospholipase A2 Phospholipase A1 O Phospholipase A2 CH2 O C CH2 R1 O R2 CH2 C O CH CH3 O CH2 O P O CH2 CH2 N+ CH3 OH CH3 Phospholipase C Phospholipase D Digestion of phospholipids Cholesterol esterase Cholesterol esterase from the pancreas reversibly hydrolyzes cholesterol esters. It has an optimum pH of 8.0 Cholesterol esters + H2O  Cholesterol + free fatty acid Digestion in the small intestines Bile Salts Bile Salts …………cont’d Recycling of bile salts Lipase Site of Actition Product release  Regulation of lipid digestion Pancreatic secretion of enzymes that degrade dietary lipids in the small intestine is hormonally regulated  Cells in the mucosa of jejunum and lower duodenum produce small peptide hormone – cholecystokinin (CCK), in response to presence of lipids and partially digested proteins  CCK is responsible for acting on the gallbladder (contraction and release of bile) and on the exocrine cells of the pancreas (release of digestive enzymes)  CCK also causes a slower release of gastric contents into the small intestine  Another small peptide hormone, secretin, is produced in response to the low pH of chyme entering the intestine  Secretin stimulates the release of a bicarbonate solution from pancreas and liver to neutralize pH of intestinal contents  At a neutral pH, the pancreatic enzymes display optimum digestive activity  Absorption of lipids End products of fat digestion are  Lysophospholipids  Monoacylglycerols  FFAs  Free cholesterol  Glycerol and Fat soluble vitamins Are solubilized in the intestine by bile acid to form micelles that fuse with plasma membrane of the intestinal villi mucosal cells of the jejunum and ileum to shuttle the content into the interior of intestinal cells  Lipid malabsorption: Steatorrhea The presence of fat in feces, at an amount more than normal (