脂脂脂脂 Lipid Metabolism
脂类代谢
Lipid Metabolism
contents
Introduction of Lipids
catabolism of Fats
biosynthesis of lipids
Lipids Water insoluble compounds Major functions
Energy storage fatty acids, triacylglycerols
Structural elements phospholipids, cholesterol
I. Introduction of Lipids
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
Saturated fatty acids
Unsaturated fatty acids
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
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
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
CH2
C
CH2
CR2
O
HO
O
O C
O
R1
C
O
R3
1
2
3
Fatty acid composition in TAG Plant: more unsaturated fatty acids Animal: largely saturated fatty acids
functions:store fuels and provide energy Yield more energy than protein and carbohydrate
Fat 9 kcal/g
CHO/protein 4 kcal/g
3. Phospholipids
Classes of phospholipids (PL)
Glycerolphospholipids – glycerol backbone Sphingomyelin – spingosine backbone
12
PhospholipidsGlycerolphospholipids
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
13
properties
Amphipathic
Sphingomyelin 鞘氨醇磷酯
Sphingosine
structure
4. Cholesterol
A polar head
A non-polar body
structure
properties Amphipathic
functions
Membrane constituents to modulate membrane fluidity Precursor of steroid hormones and bile acids
Digestionof fats
mobilization and transport of fats Oxidation of Fatty acid
Ketone Bodies
II. catabolism of Fats
Fatty acids have three sources Diet Storage in cells as lipid droplet Cellular biosynthesis
1. Digestion of fats
Processing of dietary lipids
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
Fatty acids are relased and transported through binding with serum albumin
Glycerol is converted to glyceraldehyde-3-P and enters glycolysis or gluconeogenesis
Glycerol contributes only 5% of the biologically available energy of triacylglycerols
– Saturated fatty acids– CH3-(CH2)n-CH2-CH2-
COOH • Major pathway:
-oxidation
• Minor pathway: -oxidation
-oxidation
3. Oxidation of fatty acids
Stages of fatty acid oxidation
Oxidative phosphorylation
Activation
Mitochondria
membrane
Transport
-oxidation-oxidation
-oxidation
Mitochondria matrix
Dehydrogen
Dehydrogen
Hydration
Acetyl-transfer
Acetyl-CoA
(A) Activation: conversion of fatty acid to fatty acyl-CoA
(B) Transport: via the acyl-carnitine/carnitine transporter
(C) -oxidation : four major steps
脱氢
加水
再脱氢
硫解
-oxidation : four major steps
Question : Complete Oxidation of a Palmitate
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.
( 乙酰乙酸 )
( 丙酮 ) (β- 羟丁酸 )
Formation 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
use of Ketone bodies
Ketone body formation and export from the liver
Biosynthesis of fatty acids
Biosynthesis of other lipids Triacyloglycerols
Membrane phopholipids
Cholesterol
III. Lipid Biosynthesis
+
+
H+
H+
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.
1. Biosynthesis of fatty acids
柠檬酸
Preparation step one: transfer of acetyl groups from mitochondria to cytosol
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.
The acetyl-CoA carboxylase reaction.
The long, flexible biotin arm carries the activated CO2 from the biotin carboxylase region to the transcarboxylase active site
Malonyl-CoA-ACP transacylase
Acetyl-CoA-ACP transacylase
Loading step: transfer of acetyl-CoA and malonyl-CoA to form acetyl-ACP and malonly-ACP
1.缩合
2.加氢还原 4.加氢还原
3.脱水
Four major steps in fatty acids biosynthesis
Acetyl-CoA- ACP transacetylase
Sequence of events during synthesis of a
fatty acid
-Ketoacyl-ACP synthase
-Dedroxyacyl-ACP dehydratase
Enoyl-ACP reductase
Translocation of butyryl group to Cys on KS
Malonyl-CoA -ACP transacylase
-Ketoacyl-ACP reductase
The overall process: 8 Acetyl-CoA + 7ATP + 14NADPH + 14H+
palmitate + 14 NADP+ + 8CoA + 6H2O + 7ADP + 7Pi
1. 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 + H2OPalmitoyl thioesterase
Question:how to synthesize a palmitate ?
2. Biosynthesis of fats
3. Biosynthesis of Phospholipids
Two general strategies for forming the phosphodiester bond of glycerophospholipids
The biosynthesis of sphingolipids
4. Biosynthesis of cholesterol
Summary of cholesterol biosynthesis,
The first stage Formation of mevalonate from acetyl-CoA.
The second stage Conversion of mevalonate into activated isoprene units.
The third stage Formation of squalene (30 carbons) by successive condensation
s of activated isoprene (five-carbon) units
The fourth stage Formation of squalene (30 carbons) by successive condensation
s of activated isoprene (five-carbon) units