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Biochemistry Lipid Metabolism

De novo Synthesis of Fatty Acids

Topic overview

Start with the big picture

Acetyl-CoA generated in mitochondria cannot cross the mitochondrial membrane directly, so its carbon is exported as citrate and made available in the cytosol. NADPH supplies reducing power, while acetyl-CoA carboxylase (ACC) catalyzes the committed step by forming malonyl-CoA. Fatty acid synthase uses an acetyl-CoA primer and adds two-carbon units from malonyl-CoA through a repeating reaction cycle, producing palmitate. The pathway responds to nutritional and hormonal signals: insulin and citrate activate ACC, whereas glucagon, epinephrine, AMPK phosphorylation, and palmitoyl-CoA inhibit it. Malonyl-CoA also links synthesis to oxidation by inhibiting carnitine acyltransferase I. The broader lesson covers further modification, energy requirements, physiological roles, and clinical context.

Learning objectives

What you'll learn

  • Identify the principal tissues and cellular location of fatty acid synthesis.
  • Explain how citrate transport and NADPH support cytosolic synthesis.
  • Describe ACC’s committed reaction and its major regulators.
  • Outline fatty acid synthase’s use of acetyl-CoA and malonyl-CoA.
  • Relate malonyl-CoA to the regulation of fatty acid oxidation.
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