malonylCoAmediated

Malonyl-CoA mediated refers to cellular processes whose regulation or function depends on malonyl-CoA, a central metabolite that links fatty acid synthesis with energy balance. Malonyl-CoA acts as both a substrate in lipid biosynthesis and a signaling molecule that modulates lipid oxidation and metabolic signaling. The term is often used in discussions of fatty acid biosynthesis, regulation of mitochondrial beta-oxidation, and protein post-translational modifications influenced by malonyl-CoA.

Biochemical origin and primary roles: Malonyl-CoA is formed from acetyl-CoA by acetyl-CoA carboxylase (ACC) using CO2 and ATP, primarily in the cytosol. ACC has two relevant isoforms: ACC1 drives cytosolic lipogenesis, while ACC2 is associated with mitochondria and helps regulate beta-oxidation by generating malonyl-CoA near CPT1. As an extender unit, malonyl-CoA serves as a substrate for fatty acid synthase to produce palmitate and longer fatty acids.

Regulation and metabolic significance: Malonyl-CoA inhibits carnitine palmitoyltransferase I (CPT1), reducing mitochondrial import of long-chain fatty acids and thereby suppressing beta-oxidation when lipid synthesis is favored. Energy-sensing and hormonal pathways govern malonyl-CoA levels: insulin stimulates ACC activity and raises malonyl-CoA, promoting lipogenesis, while AMP-activated protein kinase (AMPK) phosphorylates and inhibits ACC, lowering malonyl-CoA and promoting oxidation. Malonyl-CoA decarboxylase lowers malonyl-CoA levels to relieve CPT1 inhibition during energy-demanding states.

Beyond metabolism, malonyl-CoA is a donor for protein malonylation, a reversible post-translational modification that can affect enzyme activity and signaling. Some organisms use malonyl-CoA in polyketide and related secondary metabolite biosynthesis via polyketide synthases, illustrating additional contexts in which malonyl-CoA mediates cellular processes.