Cytosolic synthesis of palmitate (C16:0) from acetyl-CoA — opposite direction of mitochondrial β-oxidation. Acetyl-CoA is exported from mitochondria via citrate shuttle. Acetyl-CoA carboxylase (ACC) — RATE-LIMITING — produces malonyl-CoA (biotin-dependent; same step inhibits CPT1, preventing simultaneous synthesis + oxidation). Fatty acid synthase (FAS) is a single megaenzyme that sequentially condenses acetyl-CoA + malonyl-CoA into palmitate using NADPH (from PPP). Insulin upregulates ACC + FAS (postprandial lipogenesis). Lipogenesis inhibitors investigated for cancer (TVB-2640) and NASH.
Organ Systems
endocrine
digestive
Pathway Steps
acetyl-coa → malonyl-coa — via ACC (acetyl-CoA carboxylase) — RATE-LIMITING; biotin; also CPT1 inhibitor. Acetyl-CoA carboxylase is the rate-limiting, biotin-dependent committed step — activated by citrate, inhibited by phosphorylation (AMPK) and long-chain acyl-CoA. Its product malonyl-CoA also inhibits CPT1, shutting off β-oxidation so synthesis and breakdown don’t run at once.
malonyl-coa → palmitate — via fatty acid synthase (FAS) — megaenzyme; sequential C2 extensions; NADPH consumer. Fatty acid synthase is a multi-domain megaenzyme that iteratively condenses C2 units from malonyl-CoA, using NADPH (from the pentose-phosphate pathway) as reductant, to build palmitate (C16) — the cytosolic counterpart to mitochondrial β-oxidation.