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LIPID METABOLISM December 2007 5/3/2017 4:11 PM 1 Monogastric Digestion Challenges 1.Lipids are not water soluble 2.Triglycerides too large to be absorbed Digestive solution 1.Triglycerides mix with bile and pancreatic secretions 2.Emulsification and digestion Bile Produced in liver, stored in gallbladder Except horse Alkaline solution composed of: Bile salts Cholesterol Lecithin Bilirubin Responsible for fat emulsification Detergent action Mixed micelle formed by bile salts, triacylglycerols and pancreatic lipase. Digestion of Lipid Bile salts emulsify lipids Pancreatic lipase acts on triglycerides Triglycerides sn-2 monoglyceride + 2 fatty acids Pancreatic colipase Activated by trypsin Interacts with triglyceride and pancreatic lipase Displaces bile to allow recycling Improves activity of pancreatic lipase Pancreatic Colipase Secreted from pancreas as procolipase Activated (cleaved) by trypsin Anchors lipase to the micelle One colipase to one lipase (i.e., 1:1 ratio) Emulsification Produces small lipid spheres Greater surface area Lipases attack TG at 1 and 3 positions G Fatty Acid1 l y c e Fatty Acid2 r o l Fatty Acid3 Triglyceride Lipase 2 H20 G l y c Fatty Acid2 e r o l 2-Monoglyceride + Fatty Acid1 Fatty Acid3 2 Free Fatty Acids Digestion of Lipid Phospholipase A1 and A2 Hydrolyzes fatty acids from phospholipids Cholesterol esterase Hydrolyzes fatty acids from cholesterol esters Micelle Formation Complex of lipid materials soluble in water Contains bile salts, phospholipids & cholesterol Combines with 2-monoglycerides, free fatty acids and fat-soluble vitamins to form mixed micelles Micelle Formation Lipid Absorption simple diffusion exocytosis Short and medium chain fatty acids Overview of Fatty Acid Uptake Short- and medium-chain fatty acids Enter portal blood directly from enterocytes Bound to albumin in blood Albumin–FFA complex Oxidized in liver or elongated and used for triglyceride formation Long-chain fatty acids Form chylomicrons Drain into the lymphatics via the lacteal in mammals (no lacteal in avian small intestinal villi) Enter bloodstream at the thoracic duct Upstream from liver Slow entry into the blood Overview of Lipid Digestion in Mammals Fatty Acids β-Oxidation 5/3/2017 4:11 PM 15 Fatty Acids Beta Oxidation 5/3/2017 4:11 PM 16 5/3/2017 4:11 PM 17 Fatty Acid Translocation into Mitochondrion 5/3/2017 4:11 PM 18 Stages of Fatty Acids Beta Oxidation 5/3/2017 4:11 PM 19 5/3/2017 4:11 PM 20 5/3/2017 4:11 PM 21 5/3/2017 4:11 PM 22 5/3/2017 4:11 PM 23 5/3/2017 4:11 PM 24 5/3/2017 4:11 PM 25 β - Oxidation Fatty Acids (with odd carbon number) β - Oxidation Fatty Acids (Peroxisomes) α - Oxidation Fatty Acids ω - Oxidation Fatty Acids 5/3/2017 4:11 PM 26 Odd Chain Fatty Acids Beta Oxidation 5/3/2017 4:11 PM 27 5/3/2017 4:11 PM 28 Unsaturated Fatty Acids Beta Oxidation 5/3/2017 4:11 PM 29 Biohydrogenation of Linoleic Acid Linoleic acid (18:2) isomerase cis-9, trans-11 CLA reductase trans-11 18:1 reductase Stearic acid (18:0) Intermediate fatty acids are conjugated linoleic acids Regulation of Beta Oxidation 5/3/2017 4:11 PM 31 5/3/2017 4:11 PM 32 Carnitine Deficiency CPT-I and CPT-II Deficiency Sulfonylurea Drug Consumption Jamacaican Vomitting Sickness Dicarboxylic Aciduria Refsum's Disease Zellweger‘s Disease 5/3/2017 4:11 PM 33 Ketogenesis (Synthesis of Ketone Bodies) 5/3/2017 4:11 PM 34 5/3/2017 4:11 PM 35 5/3/2017 4:11 PM 36 5/3/2017 4:11 PM 37 5/3/2017 4:11 PM 38 Regulation of Ketogenesis 5/3/2017 4:11 PM 39 5/3/2017 4:11 PM 40 CLINICAL ASPECTS Impaired Oxidation of Fatty Acids Gives Rise to Diseases Often Associated With Hypoglycemia 5/3/2017 4:11 PM 41 Fatty Acid Synthesis (Lipogenesis) 5/3/2017 4:11 PM 42 Fatty acid synthase complex 5/3/2017 4:11 PM 43 Methyl malonyl-CoA Biosynthesis 5/3/2017 4:11 PM 44 Fatty acid synthesis: stage-1 5/3/2017 4:11 PM 45 Fatty acid synthesis: stage-2 5/3/2017 4:11 PM 46 Fatty acid synthesis: stage-3 5/3/2017 4:11 PM 47 Fatty acid synthesis: stage-4 5/3/2017 4:11 PM 48 Fatty acid synthesis: stage-5 5/3/2017 4:11 PM 49 5/3/2017 4:11 PM 50 FA Elongation System ER ( microzomes) is the local of EFA Elangase Enzyme System 5/3/2017 4:11 PM 51 Acety CoA transportion and NADPH production Pathways 5/3/2017 4:11 PM 52 5/3/2017 4:11 PM 53 Regulation of Lipogenesis Nutritional State Carbohydrate or Lipid Intake Regulation of Acetyl-CoA Carboxylase Regulation of Pyruvate Dehydrogenase Effect of Hormone 5/3/2017 4:11 PM 54 Unsaturated fatty acid Biosynthesis One unsaturated FA; Liver is the position synthesis The first local is the position Δ9 Δ9 Desaturase enzyme system in ER ( O2 + NADPH+ Cytochrome b5) Poly unsaturated FA; 5/3/2017 4:11 PM 55 5/3/2017 4:11 PM 56 5/3/2017 4:11 PM 57