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Digestion, Absorption of lipids Dpt 4th 19 Aug, 2013 overview Processing in stomach • Lingual & gastric lipase starts digestion of fatty acids with fewer than 12 carbons i.e. milk in neonates • Cystic fibrosis enzymes not able to reach intestine leading to pancreatic insufficiency • Emulsification of dietary lipids occurs in small intestine • Emulsification occurs by two simultaneous processes i) mechanical mixing by peristalsis ii)detergent property of bile salts--- Degradation by pancreatic enzymes TAG Degradation • Lipase and esterase are the enzymes removes fatty acids from carbon 1 and 3 of TAG molecules forming 2-monoacylglycerol & free fatty acids • Colipase act as zymogen and restores the activity of lipase • Drug Orlistat-----inhibits gastric, pancreatic lipases so decreases fat absorption Cholesterol ester Degradation • Cholesterol esterase produces cholesterol and free fatty acids Phospholipid degradation • Phospholipase A2 removes one fatty acid from carbon 2 of phospholipid leaving a Lysophospholipid , remaining fatty acid at carbon 1 is removed by lysophospholipase leaving Glycerylphosphoryl base excreted in feces • In response for the presence of lipids, 1)Cholecytokinin a small hormone is produced by cells of duodenum • CCK acts on gall bladder and pancreas allowing them to release bile salts and digestive enzymes 2) Secretin, another peptide hormone produced in response of low pH of chyme entering to intestine • Releases bicarbonate for appropriate pH of digestive activity Lipid absorption in intestinal mucosal cells • Primary products of lipid digestion (free fatty acids, free cholesterol, 2-monoacylglycerol) along with bile salts and fat soluble vitamins forms micelles (soluble in the aqueous environment of the intestinal lumen • hydrophilic surface of the micelles facilitates the transport of the hydrophobic lipids to brush like membrane of intestine Resynthesis • Fatty acids converted to its activated form by fatty acyl coA synthetase (thiokinase) • 2-monoacylglycerol converted into TAG through TAG synthase & other two enzyme activities Monoacylglycerol Acyltranferase & Diacylglycerol Acyltransferase • Steatorhea Lipid secretion from enterocytes • Newly formed TAG and cholesterol esters are hydrophobic in nature so they must be packaged as lipid droplets composed of phospholipids or apolipoprotein B-48 • This is necessary to increase its solubility and stability • Particles then released by exocytosis into lymphatic vesicles, this lymph is called chyle and particles named chylomicrons Use of dietary lipids by the tissues • Triacylglycerols in chylomicrons are broken down into free fatty acids and glycerol by lipoprotein lipase • Fatty acids may be transported to blood or associated with albumin until taken up by cells • Glycerol is used by liver to produce glycerol-3phosphate which can enter to glycolysis or gluconeogenesis • Hyperlipoprotenemia