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Fatty Acid Biosynthesis
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Fatty Acid Biosynthesis

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
CLINICAL CORRELATION Essential fatty acids: linoleic acid and linolenic acid cannot be synthesized endogenously.
  • Mammals cannot induce double bonds beyond C9