De novo Synthesis of Fatty Acids
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.
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.
Continue your study
Work through the complete notes and reinforce the topic with the study tools available in the full lesson.