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脂类代谢 Lipid Metabolism

脂类代谢 Lipid Metabolism. contents. Introduction of Lipids catabolism of Fats biosynthesis of lipids. I. Introduction of Lipids. Lipids Water insoluble compounds Major functions Energy storage fatty acids, triacylglycerols Structural elements phospholipids, cholesterol.

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脂类代谢 Lipid Metabolism

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  1. 脂类代谢Lipid Metabolism

  2. contents • Introduction of Lipids • catabolism of Fats • biosynthesis of lipids

  3. I. Introduction of Lipids Lipids • Water insoluble compounds • Major functions • Energy storage fatty acids, triacylglycerols • Structural elements phospholipids, cholesterol

  4. 1. Fatty acids • Basic formula: CH3(CH2)nCOOH • Carboxylic acids with hydrocarbon chains of 4-36 carbons • FAs in cells are either: • (i) part of a lipid molecule • (ii) complex with a carrier protein • (e.g. albumin on blood) • Saturated or unsaturated

  5. Unsaturated fatty acids Saturated fatty acids

  6. Fully saturated fatty acid pack into nearly crystalline arrays, stabilized by hydrophobic interaction The presence of cis double bonds interferes with the tight packing and results in less stable aggregates

  7. Some Naturally Occurring Fatty acids #C Common Name 12:0 Lauric Acid 14:0 Myristic Acid 16:0 Palmitic Acid (软脂酸) 16:1 Palmitoleic Acid 18:0 Stearic Acid (硬脂酸) 18:1 Oleic Acid (油酸) 18:2 Linoleic Acid (亚油酸) 18:3 Linolenic Acid (亚麻酸) 20:0 Arachidic Acid 20:4 Arachidonic acid (花生四烯酸) 24:0 Ligoceric Acid Essential Fatty acids

  8. 2. Triacylglycerol • Compose of three fatty acids each in eater linkage with a single glycerol • Most naturally occurring triacylglycerol contain two or more different fatty acids

  9. Fatty acid composition in TAG • Plant: more unsaturated fatty acids • Animal: largely saturated fatty acids

  10. functions:store fuels and provide energy • Yield more energy than protein and carbohydrate Fat 9 kcal/g CHO/protein 4 kcal/g

  11. 3. Phospholipids • Classes of phospholipids (PL) • Glycerolphospholipids – glycerol backbone • Sphingomyelin – spingosine backbone

  12. Phospholipids Glycerolphospholipids • Structure • Two fatty acids are attached in ester linkage to the first and second carbon of glycerol • A highly polar or charged group is attached by a phosphodiester linkage to the third carbon 12

  13. properties Amphipathic 13

  14. Sphingomyelin 鞘氨醇磷酯 • structure Sphingosine

  15. 4. Cholesterol • structure A non-polar body A polar head • properties Amphipathic

  16. functions • Membrane constituents to modulate membrane fluidity • Precursor of steroid hormones and bile acids

  17. II. catabolism of Fats • Digestionof fats • mobilization and transport of fats • Oxidation of Fatty acid • Ketone Bodies

  18. 1. Digestion of fats • Fatty acids have three sources • Diet • Storage in cells as lipid droplet • Cellular biosynthesis

  19. Processing of dietary lipids

  20. 2. Fats mobilization and transport • the levels of glucose will affect the mobilization of fats Low levels of glucose in blood trigger the mobilization of triacyglycerols . • Controlled by hormones: • Insulin • epinephrine and glucagon

  21. Fatty acids are relased and transported through binding with serum albumin

  22. Glycerol is converted to glyceraldehyde-3-P and enters glycolysis or gluconeogenesis • Glycerol contributes only 5% of the biologically available energy of triacylglycerols

  23. 3. Oxidation of fatty acids • Saturated fatty acids • CH3-(CH2)n-CH2-CH2-COOH • Major pathway: • -oxidation • Minor pathway: • -oxidation • -oxidation

  24. Stages of fatty acid oxidation Oxidative phosphorylation

  25. -oxidation Transport Dehydrogen Hydration Activation Acetyl-CoA Dehydrogen Acetyl-transfer Mitochondria membrane Mitochondria matrix -oxidation

  26. (A) Activation: conversion of fatty acid to fatty acyl-CoA

  27. (B) Transport: via the acyl-carnitine/carnitine transporter

  28. (C) -oxidation: four major steps 脱氢 加水 再脱氢 硫解

  29. -oxidation: four major steps

  30. Question : Complete Oxidation of a Palmitate

  31. 4. Ketone bodies • Include acetoacetate, D-β-hydroxybutyrate, and acetone • Acetyl-CoA in liver can be converted to keton bodies for exporting to other tissues in conditions of starvation and uncontrolled diabetes.

  32. Formation of Ketone bodies (乙酰乙酸) (丙酮) (β-羟丁酸)

  33. use of Ketone bodies • β-Hydroxybutyrate synthesized in the liver passes into the blood and thus to other tissues, and it is converted to acetyl-CoA and then used for energy production

  34. Ketone body formation and export from the liver

  35. III. Lipid Biosynthesis • Biosynthesis of fatty acids • Biosynthesis of other lipids • Triacyloglycerols • Membrane phopholipids • Cholesterol

  36. + H+ + H+

  37. 1. Biosynthesis of fatty acids • Fatty acid synthesis is not simply a reversal of the degradation pathway. • Fatty acid synthesis and degradation pathways again exemplify the principle that synthetic and degradation pathways are almost always distinct.

  38. Preparation step one: transfer of acetyl groups from mitochondria to cytosol 柠檬酸

  39. Preparation step two: Malonyl-CoA is formed from carboxylation of acetyl-CoA • Acetyl-CoA carboxylase has three functional regions: • biotin carrier protein (gray); • biotin carboxylase, which activates CO2 by attaching it to a nitrogen in the biotin ring in an ATP-dependent reaction • transcarboxylase, which transfers activated COz from biotin to acetyl-CoA, producing malonyl-CoA.

  40. The acetyl-CoA carboxylase reaction. The long, flexible biotin arm carries the activated CO2 from the biotin carboxylase region to the transcarboxylase active site

  41. Loading step: transfer of acetyl-CoA and malonyl-CoA to form acetyl-ACP and malonly-ACP Malonyl-CoA-ACP transacylase Acetyl-CoA-ACP transacylase

  42. Four major steps in fatty acids biosynthesis 3.脱水 1.缩合 2.加氢还原 4.加氢还原

  43. Sequence of events during synthesis of a fatty acid Acetyl-CoA- ACP transacetylase Translocation of butyryl group to Cys on KS Malonyl-CoA -ACP transacylase Enoyl-ACP reductase -Ketoacyl-ACP synthase -Ketoacyl-ACP reductase -Dedroxyacyl-ACP dehydratase

  44. Question:how to synthesize a palmitate ? • Seven cycles of condensation and reduction : • 1Acetyl-CoA + 7 malonyl-CoA + 14NADPH + 14H+ • palmitate + 7CO2 + 14 NADP+ + 8CoA + 6H2O • 2. Formation of seven malonyl-CoA molecules: • 7 Acetyl-CoA + 7CO2 + 7ATP 7 malonyl-CoA + 7ADP + 7Pi • 3.Palmitate-ACP + H2O Palmitate + ACP + H2O Palmitoyl thioesterase The overall process: 8 Acetyl-CoA + 7ATP + 14NADPH + 14H+ palmitate + 14 NADP+ + 8CoA + 6H2O + 7ADP + 7Pi

  45. 2. Biosynthesis of fats

  46. 3. Biosynthesis of Phospholipids Two general strategies for forming the phosphodiester bond of glycerophospholipids

  47. The biosynthesis of sphingolipids

  48. 4. Biosynthesis of cholesterol Summary of cholesterol biosynthesis,

  49. The first stage Formation of mevalonate from acetyl-CoA.

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