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
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
Essential
Fatty acids
12:0
14:0
16:0
16:1
18:0
18:1
18:2
18:3
20:0
20:4
24:0
Common Name
Lauric Acid
Myristic Acid
Palmitic Acid (软脂酸)
Palmitoleic Acid
Stearic Acid (硬脂酸)
Oleic Acid (油酸)
Linoleic Acid (亚油酸)
Linolenic Acid (亚麻酸)
Arachidic Acid
Arachidonic acid (花生四烯酸)
Ligoceric Acid
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
O
O
1
CH2 O C R1
2
R2 C O C H
3
O
CH2 O C R3
 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
CHO/protein
9 kcal/g
4 kcal/g
3. Phospholipids
 Classes of phospholipids (PL)
 Glycerolphospholipids – glycerol backbone
 Sphingomyelin – spingosine backbone
Glycerolphospholipids
Phospholipids
 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
 properties
Amphipathic
13
Sphingomyelin 鞘氨醇磷酯
 structure
Sphingosine
4. Cholesterol
 structure
A non-polar body
A polar head
 properties
Amphipathic
 functions
 Membrane constituents to modulate membrane
fluidity
 Precursor of steroid hormones and bile acids
II. catabolism of Fats
 Digestionof fats
 mobilization and transport of fats
 Oxidation of Fatty acid
 Ketone Bodies
1. Digestion of fats
 Fatty acids have three sources



Diet
Storage in cells as lipid droplet
Cellular biosynthesis
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
3. Oxidation of fatty acids
– Saturated fatty acids
–
CH3-(CH2)n-CH2-CH2-COOH
•
Major pathway:
– -oxidation
•
Minor pathway:
– -oxidation
– -oxidation
Stages of fatty acid oxidation
Oxidative
phosphorylation
-oxidation
Transport
Activation
Dehydrogen
Hydration
Dehydrogen
Mitochondria
membrane
Acetyl-transfer
Mitochondria matrix
-oxidation
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, Dβ-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.
Formation of Ketone bodies
(乙酰乙酸)
(丙酮)
(β-羟丁酸)
use of Ketone bodies
β-Hydroxybutyrate
synthesized in the liver
passes into the blood and
thus to other tissues, and
it is converted to acetylCoA and then used for
energy production
Ketone body formation and export from the liver
III. Lipid Biosynthesis
 Biosynthesis of fatty acids
 Biosynthesis of other lipids
 Triacyloglycerols
 Membrane phopholipids
 Cholesterol
+ H+
+ H+
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.
Preparation step one:
transfer of acetyl groups from mitochondria to cytosol
柠檬酸
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 ATPdependent 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
Loading step: transfer of acetyl-CoA
and malonyl-CoA to form acetyl-ACP
and malonly-ACP
Malonyl-CoA-ACP
transacylase
Acetyl-CoA-ACP
transacylase
Four major steps in fatty acids
biosynthesis
1.缩合
2.加氢还原
3.脱水
4.加氢还原
Sequence of events during
synthesis of a fatty acid
Acetyl-CoAACP transacetylase
Translocation
of butyryl group to Cys
on KS
Malonyl-CoA
-ACP transacylase
-Ketoacyl-ACP synthase
-Ketoacyl-ACP
reductase
Enoyl-ACP
reductase
-Dedroxyacyl-ACP
dehydratase
Question:how to synthesize a palmitate ?
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
3. Palmitate-ACP +
H2 O
The overall process:
7 malonyl-CoA + 7ADP + 7Pi
Palmitate + ACP + H2O
Palmitoyl
thioesterase
8 Acetyl-CoA + 7ATP + 14NADPH + 14H+
palmitate + 14 NADP+ + 8CoA + 6H2O + 7ADP + 7Pi
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 condensations
of activated isoprene (five-carbon) units
The fourth stage
Formation of squalene (30 carbons) by successive condensations
of activated isoprene (five-carbon) units