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Fatty Acid Biosynthesis

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FATTY ACID BIOSYNTHESIS

Occurs in the liver and adipose tissue (cytosol)
After a carbohydrate-rich meal (high insulin:glucagon ratio)
Not just reverse of beta-oxidation: distinct enzymes and compartments

Reactions

1. Citrate Shuttle

Acetyl CoA in mitochondrial matrix transported to cytosol as citrate
Citrate synthase: citrate from oxaloacetate and acetyl CoA (also first CAC rxn)
Citrate a marker of high intracellular energy (CAC intermediate)

2. Malonyl CoA Formation

Acetyl CoA carboxylase: adds 1 carbon to acetyl CoA to form malonyl CoA
ABC carboxylase reaction
Citrate activates rxn
Long-chain fatty acyl CoA (intermed. of FA breakdown): inhibits rxn

ABC carboxylase reactions: consume ATP, require biotin, consume CO2

Malonyl CoA synthesis in fatty acid biosynthesis
Gluconeogenesis: pyruvate carboxylase
Odd chain fatty acid oxidation: propionyl carboxylase

3. Palmitate Synthesis

Palmitate: 16-carbon fatty acid
Catalyzed by fatty acid synthase
ACP is carrier protein component of fatty acid synthase
Series of 4 reactions:

i. Condensation: acetyl-ACP + malonyl-ACP = 4-C intermediate + CO2 ii. Reduction (NADPH) iii. Dehydration: water molecule released iv. Reduction (NADPH)

First condensation = 4C molecule
6 increments x 2C (malonyl-ACP) = 12 C
Total = 16 C palmitate

4. Palmitate Modification i. Elongation: in smooth ER or mitochondria

2-carbon increments using malonyl CoA (NOT malonyl-ACP)
Each increment includes four rxn's from palmitate synthesis

ii. Desaturation: in smooth ER or peroxisomes

Fatty acyl-CoA desaturase
Short electron transport chain (requires O2 and NADPH)

CLINICAL CORRELATION Essential fatty acids: linoleic acid and linolenic acid cannot be synthesized endogenously.

Mammals cannot induce double bonds beyond C9

Fatty Acid Biosynthesis

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