How is fatty acid synthesis regulated?

Fatty acid synthesis is regulated to coordinate with energy status and dietary intake. Acetyl-CoA carboxylase (ACC), catalyzing the rate-limiting step, is regulated by: allosteric activation by citrate (indicates abundant building blocks), allosteric inhibition by palmitoyl-CoA (product feedback), phosphorylation by AMPK (inactivates ACC when energy is low), and transcriptional regulation by SREBP-1c (insulin-induced in fed state). Additional regulation: malonyl-CoA inhibits CPT-I, preventing fatty acid oxidation when synthesis is active. Hormonal control: insulin promotes synthesis (activates ACC, induces SREBP-1c), while glucagon and epinephrine inhibit (activate AMPK). This ensures synthesis occurs in energy-replete, fed conditions.