Fatty Acid

Synthesis
De Novo Fatty acid synthesis occurs primarily
in the cytoplasm of these tissues:

LIVER, KIDNEY, LUNG, BRAIN, ADIPOSE

TISSUE & MAMMARY GLAND .

 Requirements for fatty acid
synthesis
1. Acetyl CoA
2. CO2
3. Malonyl co A
4. Biotin
5. ATP
6. NADPH
7. Fatty acid synthase complex
 Fates of acetyl
CoA Acetyl coA

Cholesterol Ketone
Fatty acid bodies
synthesis
TCA cycle
• Fatty acid synthesis happens in cytoplasm.

• But the source of FA synthesis – Acetyl CoA

is present in mitochondria.

• How acetyl CoA is transferred from

mitochondria to cytosol for FA syntheis?

• Under what conditions acetyl CoA is

transferred from mitochondria to cytosol for
FA syntheis?
Acetyl–CoA units are shuttled out
of the mitochondrial matrix as
citrate
Citrate Shuttle
 Fatty acid synthase
• It is not rate limiting enzyme
• Not subjected to short term regulation
• Active only as a dimer
• Contains 2 subunits, 7 enzymes &
• 3 units
1. Condensing unit
2. Reducing unit
3. Thiolytic unit
 Reactions of fatty acid synthesis
1.Acetyl CoA carboxylase catalyzes the reaction:
acetyl CoA + HCO3- + ATP -> malonyl CoA + ADP + Pi
Enzyme-biotin
-
HCO3 + ATP
1
ADP + Pi
-
Enzyme-biotin-CO 2
O
ll 2
CH3-C-SCoA
Enzyme-biotin
acetyl-CoA
O
-
ll
O2C-CH2-C-SCoA
malonyl-CoA
Step 1a Step 1b
Acetyl CoA Malonyl CoA
Acetyl transacylase Malonyl transacylase
Step 2
Step 3
Step 4
Step 5
A new malonyl-CoA molecule combines with
the -SH of 4′-phosphopantetheine,
displacing the saturated acyl residue onto the
free cysteine - SH group.
After cycling through steps 2 – 5 six times

+ Palmitate

Elongation of fatty acid chains occur in

the endoplasmic reticulum by microsomal
fatty acid elongase system.
 Regulation of FA synthesis
• Sucrose diet will increase lipogenesis.
Fructose bypasses the phosphofructokinase
control point in glycolysis and floods the lipogenic
pathway.

• Acyl-CoA inhibits the mitochondrial tricarboxylate

transporter and PDH complex by closing the
ATP/ADP transporter in mitochondria.

• Long term regulation by changes in gene expression

governing rates of synthesis of enzymes.

• Short term regulation by allosteric and covalent

modification of enzymes.
Acetyl CoA carboxylase:
• Rate limiting enzyme
• Its prosthetic group is biotin
• Controlled by
1.allosteric regulation
2. covalent modification
• Upregulated by
citrate
insulin
• Down regulated by
palmitoyl coA
glucagon
Regulation of Acetyl CoA carboxylase:

Global Local
+ insulin + Citrate
- glucagon - Palmitoyl–CoA
- epinephrine - AMP
Insulin:
• ↑ acetyl-CoA carboxylase activity.
• ↑ availability of pyruvate for FA synthesis.
• ↑ glycerol-3-phosphate for esterification of the
newly formed fatty acids.
• converts the inactive form of PDH to the active
form in adipose tissue but not in liver.
• ↓ intra cellular cAMP levels…
Inhibts lipolysis in adipose tissue
↓sed conc. of plasma free fatty acids
(Inhibitor of lipogenesis).
 FA OXIDATION VS SYNTHESIS
OXIDATION SYNTHESIS
• Takes place in mitochondria • Takes place in cytoplasm

• Substrate in palmitate • Substrate is acetyl co A

• End product is acetyl co A • End product is palmitate

• Use NAD and FAD • Use NADPH

• Requires carnitine shuttle • Requires citrate shuttle

• Key enzyme: CAT-1 • Key enzyme: ACC

• No multienzyme complex • Multienzyme complex

• Activated by glucagon. • Activated by insulin

1. Where fatty acids are synthesised?
2. What is the rate limiting enzyme?
3. What is the source of fatty acid synthesis?
4. Which coenzyme is required for carboxylation
of acetyl coA?
5. What is citrate shuttle?
6. What is fatty acid synthase complex?
7. Which fatty acid is synthesised by denovo
synthesis?
8. Which hormone helps in lipogenesis?
9. What are the activators of acetyl coA
carboxylase?
10. What are the inhibitors of acetyl coA
carboxylase?
11.Which coenzyme is needed for fatty acid
synthesis?
12.What are the sources of NADPH?
13.Which vitamin is present in fatty acid
synthase complex?