10/18/2015 5:36 PM1 LIPID METABOLISM December 2007

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 GlycerolGlycerol Fatty Acid 1 Fatty Acid 2 Fatty Acid 3 Lipase GlycerolGlycerol Fatty Acid 3 Fatty Acid 1 Fatty Acid 2 Triglyceride 2-Monoglyceride + 2 Free Fatty Acids 2 H 2 0

Digestion of Lipid Phospholipase A 1 and A 2 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 Short and medium chain fatty acids simple diffusionexocytosis

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

10/18/2015 5:36 PM15 Fatty Acids β-Oxidation

Fatty Acids Beta Oxidation 10/18/2015 5:36 PM16

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Fatty Acid Translocation into Mitochondrion 10/18/2015 5:36 PM18

Stages of Fatty Acids Beta Oxidation 10/18/2015 5:36 PM19

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β - Oxidation Fatty Acids (with odd carbon number) β - Oxidation Fatty Acids (Peroxisomes) α - Oxidation Fatty Acids ω - Oxidation Fatty Acids 10/18/2015 5:36 PM26

10/18/2015 5:36 PM27 Odd Chain Fatty Acids Beta Oxidation

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10/18/2015 5:36 PM29 Unsaturated Fatty Acids Beta Oxidation

Biohydrogenation of Linoleic Acid Linoleic acid (18:2) cis-9, trans-11 CLA trans-11 18:1 Stearic acid (18:0) isomerase reductase Intermediate fatty acids are conjugated linoleic acids

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Carnitine Deficiency Carnitine Deficiency CPT-I and CPT-II Deficiency CPT-I and CPT-II Deficiency Sulfonylurea Drug Consumption Sulfonylurea Drug Consumption Jamacaican Vomitting Sickness Jamacaican Vomitting Sickness Dicarboxylic Aciduria Dicarboxylic Aciduria Refsum's Disease Refsum's Disease Zellweger‘s Disease Zellweger‘s Disease 10/18/2015 5:36 PM33

Ketogenesis (Synthesis of Ketone Bodies) 10/18/2015 5:36 PM34

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10/18/2015 5:36 PM39 Regulation of Ketogenesis

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CLINICAL ASPECTS Impaired Oxidation of Fatty Acids Gives Rise to Diseases Often Associated With Hypoglycemia 10/18/2015 5:36 PM41

10/18/2015 5:36 PM42 Fatty Acid Synthesis (Lipogenesis)

Fatty acid synthase complex 10/18/2015 5:36 PM43

Methyl malonyl-CoA Biosynthesis 10/18/2015 5:36 PM44

Fatty acid synthesis: stage-1 10/18/2015 5:36 PM45

10/18/2015 5:36 PM46 Fatty acid synthesis: stage-2

10/18/2015 5:36 PM47 Fatty acid synthesis: stage-3

10/18/2015 5:36 PM48 Fatty acid synthesis: stage-4

10/18/2015 5:36 PM49 Fatty acid synthesis: stage-5

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F A Elongation System ER ( microzomes) is the local of EFA Elangase Enzyme System 10/18/2015 5:36 PM51

Acety CoA transportion and NADPH production Pathways 10/18/2015 5:36 PM52

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Regulation of Lipogenesis Nutritional State Nutritional State Carbohydrate or Lipid Intake Carbohydrate or Lipid Intake Regulation of Acetyl-CoA Carboxylase Regulation of Acetyl-CoA Carboxylase Regulation of Pyruvate Dehydrogenase Regulation of Pyruvate Dehydrogenase Effect of Hormone Effect of Hormone 10/18/2015 5:36 PM54

Unsaturated fatty acid Biosynthesis One unsaturated FA; Liver is the position synthesis The first local is the position Δ 9 Δ 9 Desaturase enzyme system in ER ( O2 + NADPH+ Cytochrome b5) Poly unsaturated FA; 10/18/2015 5:36 PM55

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