Fatty Acid Metabolism

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FATTY ACID

METABOLISM
PRAKASH KHADKA
GENERAL BIOCHEMISTRY
Synthesis of TAG ( Triacyl glycerol)
Triacyl glycerols are the esters of glycerol with fatty acids.

The fats and oils that are distributed in both plants and animals
are chemically triacyl glycerols.

Steps of TAG synthesis


Three molecules of fatty acids undergo esterification with a
molecule of glycerol to form triacyl glycerol
The synthesis of TAG requires 1 molecule of DHAP (
Dihydroxy acetone phosphate ) and 3 molecules of acyl
CoA.
DHAP is obtained from glycolysis while acyl CoA is
obtained as follows :
The process of triacyl glycerol synthesis involves one molecule of
DHAP which in the presence of Glycerol-3-P dehydrogenase is
reduced to Glycerol-3-Phosphate which undergoes series of
reactions forming phosphatidic acid, diacyl glycerol and finally
triacyl glycerol (triglyceride).
Degradation of TAG
Degradation of TAG is carried out in the presence of lipase enzyme
which hydrolyse fats producing glycerols and fatty acids as :

Thus obtained fatty acids are degraded by -oxidation process to yield acetyl CoA which
enters into Kreb's cycle.

Glycerol is degraded as follow:


BIOSYNTHESIS OF FATTY ACIDS

Fatty acid synthesis takes place in the cytosol and is carried out by a
multienzyme complex called FAS (fatty acid synthase complex).
Fatty acid synthesis is the creation of fatty acids from acetyl-CoA
and NADPH through the action of enzymes called fatty acid
synthases.

Fatty acid synthesis involves one acetyl CoA and a no. of malonyl CoA
depending upon the length of fatty acids
EXTRA !!!!!!!!
• Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in
many biochemical reactions in protein, carbohydrate and
lipid metabolism.
• Its main function is to deliver the acetyl group to the citric acid
cycle (Krebs cycle) to be oxidized for energy production.
• Coenzyme A (CoASH or CoA) consists of a β-mercaptoethylamine
group linked to the vitamin pantothenic acid (B5) through an amide
linkage and 3'-phosphorylated AD
Steps
Acetyl CoA in the presence of enzyme carboxylase forms malonyl-CoA
in the presence of CO2 and ATP as follows:

Thus, acetyl CoA and malonyl CoA acts upon KS and ACP sites respectively
ACP : Acyl carrier protein

KS : ß-ketoacyl-ACP synthase
Thus formed, acetyl –KS and malonyl-ACP undergo reactions under
following steps:

1. Condensation : It involves condensation of acetyl-KS and malonyl-ACP


resulting ß--ketoacyl-ACP by decarboxylation as follows :
2. REDUCTION : It involves reduction of ß--ketoacyl-ACP to ß--
hydroxybutyryl-ACP in the presence of enzyme ß--ketoacyl-
ACP reductase as follows :

3. DEHYDRATION : It involves removal of water molecule from ß--


hydroxybutyryl-ACP resulting formation of Enoyl-ACP.
4. REDUCTION : It is the final step of fatty acid synthesis
which involves reduction of Enoyl-ACP to fatty acid
under thioesterase enzyme's action which breaks 'S-
ACAP" bond
The overall reaction for the synthesis of PALMITIC ACID (16C)
from acetyl CoA can be considered in two parts :
First the formation of 7 molecules of malonyl CoA

7 acetyl CoA + 7CO2 + 7ATP 7 malonyl CoA + 7ADP + 7 Pi

Then the 7 cycles of condensation and reduction

Acetyl CoA + 7 malonyl CoA + 14 NADPH2 Palmitic acxid + 7CO2 +


8 CoA + 14 NADP + 7 H2O

Each turn of the cycle results in the addition of a two-carbon group to the fatty
acid moiety as well as the use of one ATP, one acetyl CoA, and two NADPH.

Thus , the formation of 16C palmitic acid requires 1 acetyl


CoA and 7 malonyl CoA
DEGRADATION OF FATTY ACIDS
-oxidation of fatty acids
•-oxidation may be simply defined as the oxidation of
fatty acids on the -carbon atom.

•This results in the sequential removal of a two carbon


fragment, acetyl coA.
• Was first demonstrated by German scientist Frang
Knoop who concluded that fatty acids are oxidized by
the successive loss of 2 carbon fragments.
• -oxidation of fatty acids: The break down of
fatty acid to acetyl coA.
• Occurs in the mitochondria.
• After production acetyl CoA is fed directly
into the Kreb's cycle.

Definition : Oxidation of fatty


acids on the -carbon atom to
yield a -keto acid which undergo
cleavage to form a 2C fragment in
a form of Acetyl CoA and the fatty
acid chain shorten by 2 carbon.
• The beta oxidation of fatty acids involve three
stages:

1.Activation of fatty acids in the cytosol

2.Transport of activated fatty acids into


mitochondria

3.Beta oxidation proper in the mitochondrial matrix


1. Activation of fatty acids
• Fatty acids are to be activated before being
oxidized and it takes place in cytosol.
• Activation of fatty acids is brought about by
the enzyme fatty acyl CoA synthatase.
2. Transport of activated fatty acids
into mitochondria
• Thus formed fatty acyl CoA is then transported to
mitochondrial membrane from cytosol where -oxidation
takes place.
• It is brought about by CAT-I and CAT-II enzymes.
3. Beta oxidation proper in the
mitochondrial matrix
Energetics of FA oxidation ( eg: Palmitic acid)

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