Presentation on Fatty Acid Biosynthesis in cell (Creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes called fatty acid synthases).

1. Fatty Acid
Biosynthesis
Presented By:
Tikesh Kumar
M.Sc Zoology 1st Semester
Barkatullah University, Bhopal
Department of Zoology and Applied Aquaculture
Session: 2020–21
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2. Contents
 Introduction to Fatty Acids.
 Biosynthesis of Fatty acids.
 Result.
 Regulation.
 Conclusion.
 Reference.
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3.  Introduction: Fatty Acids
 Basic building blocks of fats (lipids).
 Fatty acids are a class of compounds containing a long
hydrophobic hydrocarbon chain and a terminal
carboxylate group.
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4. Fatty Acids
 They exist free in the body as well as fatty acyl esters in
more complex molecules such as triglycerides or
phospholipids.
Triglycerides
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5. Fatty Acids
 They are also structural components of membrane lipids
such as phospholipids and glycolipids.
 Esterified fatty acids, in the form of triglycerides are stored
in adipose cells.
 Diet, adipolysis and de novo synthesis or biosynthesis are
the sources of Fatty acids.
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6.  Biosynthesis(De Novo synthesis) of Fatty Acids
 Fatty acids are synthesized by an extra mitochondrial
system.
 This system is present in many tissues, including liver,
kidney, brain, lung, mammary gland, and adipose tissue.
 Acetyl-CoA is the immediate substrate, and free palmitate
is the end product.
 Its cofactor requirements include NADPH, ATP, Mn2+,
biotin, and HCO3– (as a source of CO2).
 Catalyzed by Acetyl Co A Corboxylase and Fatty Acid
Synthase.
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7. KR
KS
AT
ER
HD
ACP
MT
HS
HS
Structure of Fatty Acid Synthase Complex
 Each segment of the disk
represents one of the six
enzymatic activities of the
complex.
 At the center is the ACP –
acyl carrier protein - with
its phospho-pantetheine
arm ending in – SH.
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8.  Steps Of Fatty Acid Biosynthesis
 Transportation of Acetyl CoA.
 Formation of Malonyl CoA.
 First round of Fatty Acid Biosynthesis:-
A. Activation of Acetyl group.
B. Activation of Malonyl group.
 Fatty Acid biosynthesis proper.
 Chain Elongation.
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9.  Transportation of Acetyl CoA
 Nearly all acetyl-CoA used in fatty acid synthesis is formed
in mitochondria.
 Acetyl co A has to move out to cytosol.
 Intra-mitochondrial acetyl-CoA first reacts with
oxaloacetate to form citrate, in the TCA cycle.
 Citrate then passes into the cytosol by Citrate
Transporter.
 In the cytosol, citrate is cleaved by citrate lyase
regenerating acetyl-CoA.
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10.  Transportation of Acetyl Co A
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11.  Formation of Malonyl CoA.
 ATP dependent reaction.
 The reaction takes place in two steps: carboxylation of
biotin (involving ATP) and transfer of the carboxyl to
acetyl-CoA to form malonyl-CoA.
 This reaction is catalyzed by Acetyl co A carboxylase.
 The overall reaction, which is spontaneous, may be
summarized as:
HCO3- + ATP + acetyl-CoA ADP + Pi + malonyl-CoA
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12.  Formation of Malonyl CoA.
Enzyme Biotin
Enzyme Biotin Co2
Malonyl Co A
Acetyl Co A Enzyme Biotin
ATP + HCO3-
ADP + Pi
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13.  First round of Fatty Acid Biosynthesis
A). Activation of Acetyl group.
 The acetyl group from acetyl-CoA is
transferred to the Cys-SH group of
the ketoacyl ACP synthase.
 This reaction is catalyzed by acetyl-
CoA transacetylase.
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14.  First round of Fatty Acid Biosynthesis
B). Activation of Malonyl group.
 Transfer of the malonyl group to the
– SH group of the ACP is catalyzed
by malonyl- CoA ACP transferase.
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15.  Fatty Acid Biosynthesis proper
After activation, the
processes involved are-
Step 1: Condensation
Step 2: Reduction
Step 3: Dehydration
Step 4: Reduction
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16. Step 1: Condensation
 Condensation of the activated
acetyl and malonyl groups takes
place to form Acetoacetyl-ACP.
 The reaction is catalyzed by β-
ketoacyl-ACP synthase.
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17. Step 2: Reduction
 The Acetoacetyl-ACP is reduced
to β-hydroxybutyryl- ACP,
catalyzed by β-ketoacyl- ACP
reductase.
 NADPH + H+ are required for
reduction.
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18. Step 3: Dehydration
 Dehydration yields a double
bond in the product,
trans- Δ2-butenoyl-ACP.
 Reaction is catalyzed by β-
hydroxybutyryl- ACP
dehydratase.
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19. Step 4: Reduction
 Reduction of the double bond
takes place to form butyryl-
ACP.
 Reaction is catalyzed by enoyl-
reductase.
 NADPH dependent reaction.
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20.  Transfer of the growing FA chain
 Growing fatty acid chain is
transferred from the acyl
carrier protein (ACP) to Cys-
SH group.
 This reaction makes way for
the next incoming malonyl
group.
 The enzyme involved is
acetyl- CoA transacetylase.
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21.  Beginning of second round of FA Biosynthesis
 The butyryl group is on the
Cys-SH group.
 The incoming malonyl group
is first attaches to ACP.
 In the condensation step,
the entire butyryl group is
exchanged for the carboxyl
group on the malonyl
residue.
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22.  Chain Elongation
 A new malonyl-CoA molecule combines with the —SH of 4'-
phosphopantetheine, displacing the saturated acyl residue
onto the free cysteine —SH group.
 The sequence of reactions are repeated until a saturated
16-carbon acyl radical (Palmityl) has been assembled.
 Catalyzed by enzyme Thioesterase (deacylase).
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23. Chain Elongation
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24.  Result of fatty acid synthesis activity
 Seven cycles of condensation and reduction produce the
16-carbon saturated palmitoyl group, still bound to ACP.
 Chain elongation usually stops at this point, and free
palmitate is released from the ACP molecule.
 Smaller amounts of longer fatty acids such as stearate
(18:0) are also formed.
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25. Sum of Fatty acid biosynthesis reactions
 The overall reaction for the synthesis of palmitate from
acetyl CoA can be considered in two parts:
 Part 1:-
Formation of 7malonyl CoA molecules:
7Acetyl-CoA + 7CO2 + 7ATP
7malonyl CoA + 7ADP + 7Pi
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26. Sum of Fatty acid biosynthesis reactions
 Part 2:-
The seven cycles of condensation and reduction after
formation of malonyl CoA:
Acetyl-CoA + 7malonyl-CoA + 14NADPH + 14H+
palmitate + 7CO2 + 8CoA + 14NADP+ + 6H2O
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27.  Fatty Acid elongation
 Palmitate in animal cells is the
precursor of other long-
chained FAs.
 By further fatty acid chain
length is elongated through the
action of FA elongation systems
present in the smooth
endoplasmic reticulum and the
mitochondria.
Palmitate
16:0
Stearate
18:0
Oleate
Longer saturated
Fatty Acids
Elongation
Elongation Elongation
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28.  Regulation of Fatty acid biosynthesis
 The reaction catalyzed by
acetyl- CoA carboxylase is the
rate limiting step in the
biosynthesis of fatty acids.
 Long-chain fatty acid synthesis
is controlled in the short term
by allosteric and covalent
modification of enzymes and in
the long term by changes in
gene expression.
CH3–C–S–CoA
–OOC–CH2–C–S–CoA
O
II
O
II
HCO3
-
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29.  Conclusion
 Fatty acid biosynthesis takes place in cytosol and acetyl
CoA is immediate substrate.
 Free palmitate is the end product.
 It is an ATP and NADPH dependent reaction.
 Rate of reaction is regulated by acetyl CoA carboxylase.
 Net Reaction:
8Acetyl CoA + 7ATP + 14NADPH
Palmitate + 14NADP+ + 8CoA + 6H2O + 7ADP + 7Pi
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30.  Reference
 Nelson, D. L., & Cox, M. M. (2017). Lehninger principles
of biochemistry (7th ed.). W.H. Freeman.
 Biochemistry, (4th ed.). Dr. U. Satyanarayana.
 Biochemistry, (4th ed.) . Voet D, Voet JG. John Wiley &
Sons Inc.
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