LIPID METABOLISM

1. LIPID METABOLISM December 2007

2. Lipid Digestion

3. 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

4. Bile • Produced in liver, stored in gallbladder • Except horse • Alkaline solution composed of: • Bile salts • Cholesterol • Lecithin • Bilirubin • Responsible for fat emulsification • Detergent action

5. Mixed micelle formed by bile salts, triacylglycerols and  pancreatic lipase.

6. 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

7. 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)

8. Emulsification • Produces small lipid spheres • Greater surface area • Lipases attack TG at 1 and 3 positions Glycerol Fatty Acid1 Glycerol Fatty Acid1 Lipase Fatty Acid2 + Fatty Acid2 2 H20 Fatty Acid3 Fatty Acid3 2 Free Fatty Acids 2-Monoglyceride Triglyceride

9. Digestion of Lipid • Phospholipase A1 and A2 • Hydrolyzes fatty acids from phospholipids • Cholesterol esterase • Hydrolyzes fatty acids from cholesterol esters

10. 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

11. Micelle Formation

12. Lipid Absorption simple diffusion exocytosis Short and medium chain fatty acids

13. 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

14. Overview of Lipid Digestion in Mammals

15. Fatty Acids β-Oxidation

16. Fatty Acids Beta Oxidation

18. Fatty Acid Translocation into Mitochondrion

19. Stages of Fatty Acids Beta Oxidation

26. β - Oxidation Fatty Acids (with odd carbon number) • β - Oxidation Fatty Acids (Peroxisomes) • α - Oxidation Fatty Acids • ω - Oxidation Fatty Acids

27. Odd Chain Fatty Acids Beta Oxidation

29. Unsaturated Fatty Acids Beta Oxidation

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

31. Regulation of Beta Oxidation

33. Carnitine Deficiency • CPT-I and CPT-II Deficiency • Sulfonylurea Drug Consumption • JamacaicanVomitting Sickness • DicarboxylicAciduria • Refsum's Disease • Zellweger‘s Disease

34. Ketogenesis(Synthesis of Ketone Bodies)

39. Regulation of Ketogenesis

41. CLINICAL ASPECTS • Impaired Oxidation of Fatty Acids Gives Rise to Diseases Often Associated With Hypoglycemia

42. Fatty Acid Synthesis(Lipogenesis)

43. Fatty acid synthase complex

44. Methyl malonyl-CoA Biosynthesis

45. Fatty acid synthesis: stage-1

46. Fatty acid synthesis: stage-2

47. Fatty acid synthesis: stage-3

48. Fatty acid synthesis: stage-4

49. Fatty acid synthesis: stage-5