AcylCoA

Acyl-CoA refers to thioester derivatives of coenzyme A in which a fatty acyl chain is linked to CoA by a thioester bond. The term encompasses a wide range of species, from acetyl-CoA (two-carbon) to long-chain and very long-chain acyl-CoAs. These molecules act as activated forms of fatty acids and serve as central carriers of acyl groups in cellular metabolism.

Formation and activation of fatty acids occur when free fatty acids are converted to acyl-CoA by acyl-CoA synthetases. This ATP-dependent ligation yields acyl-CoA, AMP, and pyrophosphate, enabling fatty acids to participate in various pathways such as beta-oxidation, lipid synthesis, and remodeling of phospholipids and sterols. Different tissues express isoforms of acyl-CoA synthetases with preferences for specific chain lengths, providing tissue- and pathway-specific pools of acyl-CoAs.

Metabolic roles include beta-oxidation and lipid synthesis. Long-chain acyl-CoAs generally cannot cross the inner mitochondrial membrane directly and require the carnitine shuttle for transport into mitochondria, involving carnitine palmitoyltransferase 1 (CPT1), carnitine/acylcarnitine translocase, and CPT2. Within mitochondria, acyl-CoAs undergo beta-oxidation to generate acetyl-CoA and reduced cofactors that feed the TCA cycle and oxidative phosphorylation. In the cytosol, acetyl-CoA is a substrate for fatty acid synthesis, with malonyl-CoA acting as a key allosteric regulator that inhibits CPT1 and beta-oxidation. Peroxisomes also perform beta-oxidation on very long-chain acyl-CoAs, shortening them for transfer to mitochondria.

Acyl-CoAs thus integrate energy production, lipid biosynthesis, and membrane remodeling, with their pool size and composition regulated by cellular energy status and nutrient availability.