Professional Documents
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4. Lipid Biosynthesis
5. Regulation and pathology of
lipid metabolism
1.Transport of Acetyl-CoA to
cytoplasm
2. Synthesis of malonyl-CoA
Fatty acid
synthetase
phosphopantetheine,
binds the growing fatty acyl
chain during the condensation
and reduction reactions of the
1 acethyl-transacylase
2 malonyl-transacylase
3 beta-ketoacyl-ACP-synthase
Decarboxilation
4 beta-ketoacyl-ACP-reductase
5 beta-hydroxyacyl-ACP-dehydrase
6 enoyl-ACP-reductase
7 ACP-acyltransferase
8 palmitoil-thio-esterase
=
Palmitate + 7 CO2 + 14 NADP + 8 HSCoA
For longer fatty acids there is a fatty acid elongation system localized on
the ER. The same reactions occur as in the Synthetase, but now have
individual enzymes. Palmitate is first activated to palmitoyl-CoA, then
interact with malonyl-CoA. The major product is stearoyl-CoA.
liver
enzyme monooxigenase
Biosynthesis of Triacylglycerols
and Glycerophospholipids
Triacylglycerols and
Glycerophospholipids are
synthesized from common
precursors:
Active Glycerol (Glycerol-3phosphate);
Active Fatty Acids (Acyl-CoA);
Phosphatidic acid
Triacylglycerols Glycerophospholipids
In the pathway to
triacylglycerols:
1. Phosphatidic acid is
hydrolyzed to form a 1,2diacylglycerol
2. Diacylglycerols are then
converted into
triacylglycerols by
esterification with a third fatty
acyl-CoA.
Synthesis of
Glycerophospholipids
Synthesis of Phosphatidil
choline
Salvage
pathway
choline
is reused
("salvaged") by being
phosphorylated then
converted into CDPcholine by condensation
with CTP.
A diacylglycerol displaces
pathway converts
ethanolamine obtained in
Biosynthesis of Cholesterol
Cholesterol is an essential molecule in many
animals, including humans
Cholesterol is founded in the structure of many
membranes
Cholesterol is a precursor of steroid hormones
vitamin D and bile acids:
Biosynthesis of Cholesterol
Takes place in a liver of adult humans
Biosynthesis of cholesterol may be divided
Acyl-CoA-cholesterol acyl
transferase (ACAT).
Acyl-CoAcholesterol acyl transferase
Plasma lipoproteins
Plasma lipoproteins, macromolecular
complexes of specific carrier proteins
called apoproteins with various
combinations of phospholipids,
cholesterol, cholesteryl esters, and
triacylglycerols
Differing combinations of lipids and
proteins produce particles of different
densities, ranging from very low-density
lipoproteins (VLDL) to high-density
Anatomy of a Lipoprotein
The principal lipid
components are
triglycerides,
cholesterol, cholesteryl
esters and
phospholipids. The
hydrophobic core of the
particle is formed by
the triglycerides and
cholesteryl esters. All
Lipoproteins
Various combinations of lipid and protein produce
particles of different densities. They are:
chylomicrons,
very low-density lipoproteins (VLDL),
low-density lipoproteins (LDL),
high-density lipoproteins (HDL).
chylomicro
n
Density (g/ml) <0.95
VLDL
IDL
LDL
HDL
0.950
1.006
1.006
1.019
1.019
1.063
1.063
1.210
15
20
4055
triglycerides
83
50
31
10
free cholesterol 2
cholesteryl
esters
phospholipids
12
23
42
1220
22
22
22
A-I, A-II,
C-I, C-II,
C-III, D,
E
Apoprotein
composition
3
7
20
B-100, CA-I, A-II,
B-48, C-I, I,
C-II, C-III C-II, C-III,
E
B-100, C-I,
C-II, C-III, B-100
E
Chylomicrons
Chylomicrons are the
largest of the lipoproteins
and the least dense,
containing a high proportion
of triacylglycerols (80-90%)
Chylomicrons are
synthesized in the
endoplasmic reticulum of
epithelial cells of the small
intestine
Chylomicrons carry fatty
Regulation of Triacylglycerols
synthesis
Familial hypercholesterolemia
In the human genetic disease known as
familial hypercholesterolemia, blood levels of
cholesterol are extremely high, and afflicted
individuals develop severe atherosclerosis in
childhood.
The LDL receptor is defective in these
individuals, and the receptor-mediated
uptake of cholesterol carried by LDL does not
occur.
Consequently, cholesterol obtained in the diet
is not cleared from the blood; it accumulates
Atherosclerosis
When the cholesterol synthesized and
obtained in the diet exceeds the amount
required for the synthesis of membranes, bile
salts, and steroids
pathological accumulations of cholesterol in
blood vessels (atherosclerotic plaques) can
develop in humans, resulting in obstruction of
blood vessels (atherosclerosis).
Atherosclerosis
Atherosclerosis
Atherosclerosis
Atherosclerosis
Atherosclerosis