3ketoacylCoA

3-ketoacyl-CoA, also called beta-ketoacyl-CoA, is a thioester of coenzyme A attached to a fatty acyl chain that bears a carbonyl group at the beta (third) carbon. It is an intermediate in the beta-oxidation pathway, the primary process by which fatty acids are degraded to acetyl-CoA in many tissues.

In mitochondrial beta-oxidation, 3-hydroxyacyl-CoA dehydrogenase oxidizes 3-hydroxyacyl-CoA to 3-ketoacyl-CoA using NAD+ as the electron acceptor, producing NADH. The resulting 3-ketoacyl-CoA is then cleaved by thiolase (beta-ketothiolase) to yield one molecule of acetyl-CoA and a shortened acyl-CoA two carbons shorter. This shortening step repeats for each two-carbon unit until a final acetyl-CoA or longer-chain products are produced. Peroxisomal beta-oxidation performs a similar sequence, particularly for very long-chain fatty acids, with enzyme variants adapted to the peroxisomal environment.

Because 3-ketoacyl-CoA is an intermediate in a rapid sequence of reactions, it is not typically accumulated or isolated under normal physiological conditions. The specific chain length of 3-ketoacyl-CoA depends on the original fatty acid, resulting in a family of related intermediates throughout the beta-oxidation cycle.

Overall, 3-ketoacyl-CoA serves as a key transitional species linking the oxidation of hydroxylated acyl-CoA to the thiolytic cleavage that shortens the fatty acid chain, enabling efficient energy extraction from fatty acids.