Fatty acid synthesis occurs through a repeated cycle of condensation, reduction, dehydration, and reduction reactions. Acetyl-CoA is carboxylated to malonyl-CoA by the enzyme acetyl-CoA carboxylase, providing the two-carbon building blocks. The fatty acid synthase complex catalyzes the cycle of reactions, with the growing fatty acid chain attached to an acyl carrier protein. Typically 16 cycles produce palmitate, which is then released from the complex. Key cofactors include NADPH, ATP, biotin, and bicarbonate. Fatty acid synthesis takes place in the cytoplasm of tissues like liver, adipose, and lactating mammary

1. FATTY ACID SYNTHESIS
BY GUNVEEN, NIKITA, PRAKRITI, SHERYA AND RIYA
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2. • Fatty acids are compounds containing a long
hydrophobic hydrocarbon chain and a
terminal carboxylate group.
• They are structural components of
membrane lipids such as phospholipids and
glycolipids.
• They are obtained from our diet, adipolysis
and de novo synthesis.
• Carbohydrates, proteins and other
molecules obtained from diet in excess of
the body’s need can be converted to fatty
acids, which are stored as triglycerides.
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3. De novo Fatty
Acid Synthesis
• Fatty acids are synthesized by an
extra mitochondrial system.
• This system is present in many
tissues, including liver, kidney
,brain,lungs mammary gland and
adipose tissue.
• Acetyl-CoA is the immediate
substrate, and free palmitate is the
end product
• Its cofactor requirements include
NADPH, ATP, Mn+2, biotin and HCO3-
• HCO3 is used as a source of co2.
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4. LOCATION OF
FATTY ACID
SYNTHESIS
FA synthase complex is found
exclusively in the cytosol

5. Acetyl CoA- The
Main Component Of
Fatty Acid Synthesis
• Acetyl CoA, which is the precursor for fatty acid
synthesis is produced from pyruvate, ketogenic
amino acids, fatty acid oxidation and by alcohol
metabolism.
• It is a substrate for TCA cycle and precursor for
fatty acids, ketone bodies and sterols.
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6. Enzymes and cofactors involved in the
process of Fatty Acid Synthesis
STAGES OF FATTY ACID SYNTHESIS :
• Transport of acetyl CoA and NADPH into cytoplasm
• Conversion of acetyl CoA to malonyl CoA
• Reactions of fatty acid synthase complex
Two main enzymes are involved in fatty acid synthesis :-
1. Acetyl CoA carboxylase
2. Fatty acid synthase
Both these enzymes are multienzyme complexes
• Coenzymes and cofactors are :-
1. Biotin
2. NADPH
3. Mn++
4. Mg++
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7. Fatty acid synthase
complex
• The Fatty Acid Synthase Complex is a polypeptide containing seven enzyme activities
• In bacteria and plants, the individual enzymes of the fatty acid synthase system are
separate, and the acyl radicals are found in combination with a protein called the acyl
carrier protein (ACP)
• In yeast mammals and birds the synthase system is a multienzyme polypeptide complex
that incorporates ACP, which takes over the role of CoA.

9. ● The enzyme forms a dimer with two identical subunits.
● each subunit consists of 3 domain having in total 7 enzymes.
● These functionally active subunits lie in antiparallel orientation.
The three domains are:-
❖ 1st domain - CONDENSING UNIT
Beta-keto acyl synthase (KS) ; Acetyl transacylase (AT) and Malonyl transacylase (MT)
❖ 2nd domain - REDUCTION UNIT
Dehydratase (DT) ; Enoyl reductase (ER) and Beta-ketoacyl reductase (R).
This domain also contains Acyl carrier protein (ACP).
❖ 3rd domain - RELEASING UNIT
Thio-esterase (TE).
● The first domain acts as an initial binding site. the 3rd domain releases the fatty acid synthesised.
● The two subunits independently operate and both can synthesize fatty acid simultaneously.

10. IMPORTANCE OF MULTIENZYME
COMPLEX
★ Multienzyme complex helps form compartmentalization of the process within
the cell. this removes the consideration for permeability barriers.
★ Synthesis of all enzymes in the complex is coordinated since it is encoded by a
single gene. So all the enzymes are in equimolar concentration which helps
increase the efficiency of the process in which these are involved.

11. Steps of
fatty acid
synthesis
• Step 1 is the input to fatty acid synthesis in acetyl-CoA,
which is carboxylated to malonyl CoA. The reaction is
catalyzed by Acetyl CoA carboxylase.
• ATP dependent carboxylation provides energy input.
• The CO2 is lost later during condensation with the
growing fatty acid.
• The spontaneous decarboxylation drives the condensation
reaction.
• As with other carboxylation reactions, the enzyme
prosthetic group is biotin
• The reaction takes place in two steps :
• The biotin carboxylase domain catalyzes the ATP
dependent carboxylation of biotin ( which is attached to a
carrier protein ) using bicarbonate as a CO2 donor.
• In the second reaction, the carboxyl group is transferred
from biotin to acetyl CoA to form malonyl CoA.

13. Overall reaction

14. ► The carboxylation reaction is driven to completion by the hydrolysis of ATP
► The Acetyl CoA carboxylase is the rate limiting enzyme of the pathway and is under
tight short term control.
► Regulation of Acetyl CoA carboxylase:
► Positively regulated by:
► Citrate (allosterically) and dephosphorylation of the enzyme
► Negatively regulated by:
► Palmitoyl CoA ( endproduct regulation) and phosphorylation of the enzyme
(through glucagon-cAMP cascade)
► the further steps are catalyzed by enzyme collectively known as fatty acid synthase
complex.

15. Assembly of long chain fatty acids
• Once malonyl-CoA is synthesized, long carbon fatty acid chains may be
assembled in a repeating four step sequence
• With each passage through the cycle the fatty acyl chain is extended by two
carbons.
• When the chain reaches 16 carbons, the product palmitate leaves the cycle.

16. Function of
the prosthetic
group of the
ACP
► It serves as a flexible arm, tethering
the growing fatty acyl chain to the
surface of the synthase complex.
► Carrying the reaction intermediates
from one enzyme active site to the next

17. Activation of the acetyl group
► The acetyl group from acetyl-CoA is transferred to the Cys-SH group of the
beta-ketoacyl ACP synthase
► This reaction is catalyzed by acetyl-CoA transacetylase

18. Activation of malonyl group
Transfer of the malonyl
group to the SH group of
the ACP is catalyzed by
malonyl CoA ACP
transferase
The charged acetyl and
malonyl groups are now
in close proximity to
each other

19. Series of
Reactions
After activation, the processes involved are :-
CONDENSATION
REDUCTION
DEHYDRATION
REDUCTION
These steps are repeated till a fatty acid with 16
carbon atoms is synthesized.

21. STEP 1 :
CONDENSATION
Activated acetyl and malonyl
groups condense to form
Acetoacetyl-ACP .
The reaction iscatalyzed by β-
ketoacyl-ACP synthase.

22. STEP 2 : REDUCTION
Acetoacetyl-ACP is reduced toβ
-hydroxy butyryl-ACP.
The reaction is catalyzed by β-
ketoacyl- ACP reductase.
NADPH +H+are required

23. STEP 3 : DEHYDRATION
Dehydration yields a double bond in the product,
trans-Δ2-butenoyl-ACP
Reaction is catalysed by β-hydroxybutyryl-ACP
dehydratase

24. STEP4 : REDUCTION
Trans-Δ2-butenoyl-ACP is
reduced to form Butyryl
ACP.
The reaction is catalysed by
enzyme Enoyl Reductase.

25. The growing chain is transferred from the acyl
carrier protein
•This reaction makes way for the next incoming
malonyl group.
•The enzyme involved is acetyl-CoAtransacetylase

26. Beginning of the second round
of the fatty acids synthesis
• The butyryl group is on the Cys-
SH group.
• The incoming malonyl group is
first attached to ACP.
• In the condensation step, the
entire butyryl group is
exchanged for the carboxyl
group on the malonyl residue.

27. The result of fatty acyl synthase 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 by hydrolytic activity in the
synthase complex.
 Smaller amounts of longer fatty acids such as stearate (18:0)
are also formed
 In mammary gland, there is a separate Thioesterase specific
for acyl residues of C8, C10 or C12,which are subsequently found in
milk lipids.

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