MalonyyliCoA

Malonyl-CoA is the coenzyme A thioester of malonic acid and a central metabolite in lipid metabolism. It functions as the two-carbon donor in fatty acid synthesis, enabling the elongation of acyl chains via the fatty acid synthase (FAS) pathway. In many organisms, malonyl-CoA is formed from acetyl-CoA by the carboxylation reaction catalyzed by acetyl-CoA carboxylase (ACC), requiring ATP and biotin as a cofactor.

In animals, two ACC isoforms exist: ACC1 in the cytosol for lipogenesis and ACC2 associated with mitochondria to regulate fatty acid oxidation. The cellular concentration of malonyl-CoA regulates mitochondrial fatty acid import by inhibiting carnitine palmitoyltransferase 1 (CPT1), thereby coupling lipid synthesis with energy status. Malonyl-CoA is also consumed in subsequent steps of fatty acid biosynthesis by the fatty acid synthase complex, which decarboxylates malonyl-CoA during chain elongation.

Regulation and degradation: ACC activity is modulated by phosphorylation (e.g., AMP-activated protein kinase inhibits ACC) and by allosteric effectors such as citrate (activator) and long-chain fatty acyl-CoAs (inhibitors). Malonyl-CoA can be degraded by malonyl-CoA decarboxylase (MCD) to acetyl-CoA, lowering malonyl-CoA levels and relieving CPT1 inhibition to permit beta-oxidation. The balance of synthesis and decarboxylation links lipid production with fatty acid breakdown.

In bacteria and plants, malonyl-CoA is used by type II FAS and by polyketide synthases as an extender unit; in vertebrates, it serves primarily as a regulator of lipid metabolism. Dysregulation of malonyl-CoA metabolism has implications for energy homeostasis and metabolic diseases.