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CHAPTER 7 LIPID METABOLISM
Lecture 1 Lipids and their functions
Lecture 2 Lipid biosynthesis
Lecture 3 Fats/ Triacylglycerols catabolism
LECTURE 1
LIPIDS IN AND THEIR
FUNCTIONS
Chapter 9
What are lipids?



Lipids are a broad group of naturally-occurring
molecules which includes fats, triacylglycerols, waxes,
sterols, fat-soluble vitamins (such as vitamins A, D, E
and K) , phospholipids, glycolipids, and others .
Lipids molecules are rich in carbon and hydrogen but
contain relatively few oxygen atoms.
Lipids are insoluble in water.
Structural relationships of the major classes of lipids.
Figure 9.1 Principles of Biochemistry, 5/e(© 2012 Moran & Horton)
Fatty Acids

The simplest lipids are fatty
acids—these are long-chain
hydrocarbons with a
carboxylate group at one end.
Structures of three C18 fatty acids
Figure 9.3 Principles of Biochemistry, 5/e(© 2012 Moran & Horton)
The existence of lipids
Peanut
Rapeseed
Sesame
sunflower
Soybean


Plants：mainly in fruits and seeds .
Fat accounts for approximately 40-50%
 Animals：mainly in adipose tissue
The main biological functions of lipids

Energy storage: The complete oxidation of fatty
acids provides high caloric content, about 9 kcal/g,
compared with 4 kcal/g for the breakdown of
carbohydrates and proteins.
The main biological functions of lipids cont’

Cell membrane structure
The glycerophospholipids, are the main structural
component of biological membranes, other nonglyceride lipid components such as sphingomyelin ,
and sterols, are also found in biological membranes .
The main biological functions of lipids cont’

Signals, cofactors, and pigments
Some types of lipids, although present in relatively
small quantities, play critical roles as cofactors or
signals.
Lipidic conjugated dienes serve as pigments in
flowers and fruits and give bird feathers their striking
colors.
The early 21st century has
seen the development of a
global epidemic of obesity,
which is caused by a number
of factors including
willpower, lifestyle and
genetics.
Severe obesity can make you dead, it
can make you sick, it can make you
sad, it can make you alone, it can
make you poor.
Lecture 2 Lipid biosynthesis
In animal tissues, triacylglycerols synthesized from two
precursors (fatty acyl–CoA and L-glycerol 3-phosphate) and
several biosynthetic steps.
Glycerol 3-phosphate synthesis
Biosynthesis of fatty acids


Fatty acids are formed by the action of Fatty acid
synthases from acetyl-CoA and malonyl-CoA
precursors
The formation of malonyl-CoA from acetyl-CoA is
an irreversible process, catalyzed by acetyl-CoA
carboxylase.
Fatty acid synthesis involve three stages



Transport of acetyl-CoA into the cytosol
Carboxylation of acetyl-CoA to form malonylCoA
The elongation cycle of fatty acid synthesis
Transport of acetyl-CoA into the cytosol


In nonphotosynthetic eukaryotes, nearly all the acetyl-CoA
used in fatty acid synthesis is formed in mitochondria from
pyruvate oxidation and from the catabolism of the carbon
skeletons of amino acids.
The mitochondrial inner membrane is impermeable to
acetyl-CoA, so an indirect shuttle transfers acetyl
group equivalents across the inner membrane.
Carboxylation of acetyl-CoA to form malonylCoA

The formation of malonyl-CoA from acetyl-CoA is
an irreversible process, catalyzed by acetyl-CoA
carboxylase.
The elongation cycle of fatty acid synthesis

In all organisms, the long carbon chains of fatty acids are
assembled in a repeating four-step sequence, catalyzed by a
system collectively referred to as fatty acid synthase.

Acyl carrier protein (ACP) is
the shuttle that holds the
system together. The E.coli
ACP is a small protein (Mr
8,860) containing the
prosthetic group 4phosphopantetheine.
Synthesis of malonyl ACP from malonyl CoA and acetyl ACP from acetyl CoA.
Step1: Condensation
Step2: Reduction
Step3: Dehydration
Step4: Reduction
The overall process of palmitate synthesis.

Fatty Acid Synthesis Occurs in the Cytosol of Many Organisms
but in the Chloroplasts of Plants
Fatty Acid Extension and Desaturation

Long-chain saturated
fatty acids are
synthesized from
palmitate
Desaturation of Fatty Acids Requires a
Mixed-Function Oxidase
Oleic acid, 18:1（△9）
Linoleic acid
Linolenic acid
Arachidonic acid ,20（△5,8,11,14）

The double bond is introduced into the fatty acid
chain by an oxidative reaction catalyzed by fatty
acyl–CoA desaturase.
Lecture 3 Fats/ Triacylglycerols catabolism
The degradation of triacylglycerols
Lipase
triacylglycerols + 3H2O
glycerol + 3 fatty acids
Glycerol metabolism


Glycerol is converted to glyceraldehyde-3-P, and
enters glycolysis or gluconeogenesis.
95% of energy of fat from fatty acids, 5% from
glycerol.
Fatty acid oxidation



CH3-(CH2)n-CH2-CH2-COOH
Major pathway:
-oxidation
Minor pathway:
-oxidation
-oxidation
Oxidation of Unsaturated fatty acids
Oxidation of odd-carbon fatty acids
β-Oxidation
In 1904, Franz Knoop fed dogs labeled at their -carbon
atoms of even-numbered- and odd-numbered FAs by a
benzene ring and isolated the phenyl-containing
metabolic products (glycine adduct) from their urine
(phenylaceturic acid and hippuric acid ).
FAs
ż
̼±½Ö¬Ëá
Ææ
̼±½Ö¬Ëá
CH 2CH 2CH 2CH 2CH 2COOH
CH 2CH 2CH 2CH 2COOH
CH 2CH 2CH 2COOH
CH 2CH 2COOH
CH 2COOH
COOH
苯乙酸
O
CH 2C NHCH 2COOH
±½ÒÒ
ÄòËá
(±½ÒÒ
ËáÑÜÉúÎï )
苯甲酸
O
C NHCH 2COOH
ÂíÄòËá
(±½¼×ËáÑÜÉúÎï )
β-oxidation is the process by which fatty acids, in
the form of Acyl-CoA molecules, are broken down
in mitochondria and/or in peroxisomes to
generate Acetyl-CoA.
The β- oxidation of fatty acids involve three stages



Activation of fatty acids in the cytosol
Transport of fatty acids into mitochondria
β- oxidation proper in the mitochondrial matrix
Activation of fatty acids in the cytosol
O
RC OH + HSCoA
ATP AMP+PPi
O
RC ¡« SCoA
Ö¬
õ£CoAºÏsynthetases
³Éø
Acyl-CoA
Ö¬õ£CoA
2ATP lost ！
Fatty acids are linked to coenzyme A before they are
oxidized
Transport of fatty acids into mitochondria need
carnitine shuttle
L-carnitine
The oxidation of saturated fatty acids has four
basic steps




Dehydrogenation
Hydratation
Dehydrogenation
Thiolysis
Dehydrogenation
O Acyl-CoA
dehydrogenase
Ö¬õ£CoAÍÑÇâø
RCH2CH2CH2C SCoA
RCH2C
fatty Acyl-CoA
FAD
FADH2
H
H O
C C
SCoA
Trans-∆2-Enoyl-CoA
Hydratation
H O
RCH2C C C
H
H2O
OH
O
SCoA
RCH2 CH CH C SCoA
enoyl-CoA
hydratase
Ï©Ö¬õ£CoAË®ºÏø
trans-∆2-enoyl-CoA
L-β-hydroxyacyl-CoA
Dehydrogenation
L-hydroxyacyl-CoA dehydrogenase
OH
O
Ï©Ö¬õ£CoAÍÑÇâø
RCH2 CH CH C SCoA
NAD
L-β-hydroxyacyl-CoA
O
O
RCH2 C CH C SCoA
+
NADH + H+
β-ketoacyl-CoA derivative
Thiolysis
O
O
Thiolase
Áò½âø
RCH2 C CH C SCoA
O
O
RCH2C SCoA + CH3C SCoA
CoASH
Thiolysis by a second CoA molecule to form Acetyl CoA and
Acyl-CoA shortened by two carbon atoms, is catalyzed by βketothiolase.
Activation
Transportation
Mitochondria membrane
Dehydrogenation
Hydration
β-Oxidation
Cytoplasmic
Dehydrogenation
Thiolysis
Acetyl-CoA
Mitochondrial matrix
The overall equation is:
The glyoxylate cycle

The glyoxylate cycle is an anabolic metabolic pathway
occurring in plants, and several microorganisms, such
as E. coli and yeast.

Germinating seeds can therefore convert the carbon
of stored lipids into glucose.

Isocitrate lyase and
malate synthase are
unique to the glyoxylate
cycle. Notice that two
acetyl groups (pink) enter
the cycle and four
carbons leave as
succinate (blue).
The net reaction for the GAC is as follows：
2CH3CO-SCOA+2H2O+NAD+
Succinate+2CoASH+NADH+H+
FIGURE 16–21 Electron micrograph of a germinating cucumber seed,
showing a glyoxysome, mitochondria, and surrounding lipid bodies.

In germinating seeds, the enzymatic
transformations of dicarboxylic and
tricarboxylic acids occur in three
intracellular compartments:
mitochondria, glyoxysomes, and the
cytosol.

There is a continuous interchange of
metabolites among these
compartments.

The reactions of the glyoxylate
cycle (in glyoxysomes) proceed
simultaneously, and mesh with,
those of the citric acid cycle (in
mitochondria), as intermediates
pass between these compartments.
Lipids of oil
plant seeds
Lipid Metabolism
Acetyl-CoA
Glyoxylate cycle
Succinic acid + Oxaloacetate
Gluconeogenesis
Sugar

Coordinated regulation of
glyoxylate and citric acid cycles.

The partitioning of isocitrate
between the citric acid cycle
and the glyoxylate cycle is
controlled at the level of
isocitrate dehydrogenase,
which is regulated by
reversible phosphorylation.