De Novo Fatty Acid Synthesis

DE NOVO FATTY ACID SYNTHESIS (LIPOGENESIS)

• De Novo fatty acid synthesis is cholesterol synthesis.
• It is synthesized in cytosol.
• It occurs in liver, lactating mammary gland, kidney, brain, lungs and adipose tissues.
• Cofactors required are– NADPH, Mn+2 , Biotin and HCO3- .
• The basic bulding block is acetyl CoA of fatty acid synthesis.
• Pathway takes place in 3 steps-

1. Transport acetyl- CoA to cytosol
2. Conversion of acetyl CoA to malonyl- CoA by carboxylation.
3. Reactions of fatty acid synthase

Transport of acetyl CoA to cytosol-

• Glucose is the primary substrate for lipogenesis and acetyl CoA.
• Acetyl CoA + oxaloacetate —à citrate
• Citrate cleaves into acetyl CoA and oxaloacetate in cytosol by ATP Citrate lyase.

Conversions of acetyl CoA to malonyl CoA-

• Production of Malonyl CoA is the initial and rate limiting step catalysed by Acetyl CoA carboxylase.
• Malonyl CoA is a 3- carbon compound is an activated form in the cycle. (committed step)
• Acetyl CoA carboxylase requires B complex vitamin Biotin.

Reactions catalyzed by fatty acid synthase-

• Fatty acid synthase is a multienzyme complex made of 6 enzymes and acyl carrier protein (ACP).
• ACP contains vitamin Panthotenic acid.
• 6 enzymes are-

1. E1- acyl transacylase
2. E2- malonyl transacylase
3. E4- ketoacyl reductase
4. E5- hydratase
5. E6- Enoyl reductase
6. E7- Thioesterase

 Reactions of fatty acid synthase– 3 stages-

1. Priming reactions- (total 4 carbon atoms are incorporated)

• Malonyl transacylase catalyzes to phosphopantetheine – SH group  of ACP to form acetyl- malonyl enzyme.

2. Elongation reaction-

• Includes condensation, reduction, dehydration and reduction.

1. Condensation by 3 ketoacyl synthase– malonyl moiety liberates CO2 molecule forming ketoacyl enzyme.
2. Reduction by 3- ketoacyl reductase- NADPH serves as a reductant (electron donor).
3. Dehydration by dehydratase
4. Reduction by enoyl reductase

• Main source of NADPH is the pentose phosphate pathway (HMP shunt).

Exam Question