acetylCoACoArelaatio

Acetyl-CoA carboxylation, or the acetyl-CoA carboxylation reaction, is a biotin-dependent carboxylation step that converts acetyl-CoA to malonyl-CoA. This reaction is a key regulatory point in de novo fatty acid biosynthesis across bacteria, plants, and animals. The overall reaction is acetyl-CoA plus bicarbonate (as CO2) and ATP to yield malonyl-CoA, with ADP and inorganic phosphate as byproducts.

The reaction is catalyzed by acetyl-CoA carboxylase (ACC), a biotin-containing enzyme complex. In most eukaryotes ACC is a multifunctional enzyme comprising biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase activities within a single polypeptide. In bacteria, ACC can be organized as multi-subunit assemblies. The mechanism proceeds in two partial steps: first, biotin is carboxylated by ATP to form carboxybiotin; then the carboxyl group is transferred from carboxybiotin to acetyl-CoA to produce malonyl-CoA.

Regulation of ACC is complex and tightly linked to cellular energy and lipid needs. Citrate can activate ACC by promoting its polymerization, increasing activity, while long-chain fatty acyl-CoAs provide feedback inhibition. In mammals, phosphorylation by AMP-activated protein kinase (AMPK) inhibits ACC, whereas dephosphorylation activates it. Hormonal signals related to feeding and fasting also influence ACC activity, aligning fatty acid synthesis with energy status.

Functionally, malonyl-CoA serves as the two-carbon donor in fatty acid synthase–driven elongation and also inhibits the mitochondrial carnitine shuttle, linking fatty acid synthesis to energy metabolism. Dysregulation of acetyl-CoA carboxylation is implicated in metabolic disorders and cancer, making ACC a target of biomedical research and potential therapeutic strategies.