1. 脂类代谢 Lipid Metabolism

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

3. I. Introduction of 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 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

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: Lauric Acid
14: Myristic Acid
16: Palmitic Acid (软脂酸)
16: Palmitoleic Acid
18: Stearic Acid (硬脂酸)
18: Oleic Acid (油酸)
18: Linoleic Acid (亚油酸)
18: Linolenic Acid (亚麻酸)
20: Arachidic Acid
20: Arachidonic acid (花生四烯酸)
24: 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. 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 properties Amphipathic 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. Mitochondria membrane
-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. Malonyl-CoA is formed from carboxylation of acetyl-CoA
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
1.缩合
3.脱水
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
-Ketoacyl-ACP synthase
Enoyl-ACP
reductase
-Ketoacyl-ACP
reductase
-Dedroxyacyl-ACP
dehydratase

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

46. 2. Biosynthesis of fats

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

48. The biosynthesis of sphingolipids

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

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

51. The second stage
Conversion of mevalonate into activated isoprene units.

52. The third stage
Formation of squalene (30 carbons) by successive condensations of activated isoprene (five-carbon) units

53. The fourth stage
Formation of squalene (30 carbons) by successive condensations of activated isoprene (five-carbon) units