KetoacylCoA

Ketoacyl-CoA, also known as beta-ketoacyl-CoA or 3-ketoacyl-CoA, refers to a family of CoA thioesters in which the acyl chain bears a keto group at the beta (third) carbon. These compounds are intermediates in fatty acid metabolism and related pathways, with the length of the acyl chain varying.

Biochemical role

In fatty acid beta-oxidation, a sequence of reactions converts acyl-CoA to beta-hydroxyacyl-CoA, then to 3-ketoacyl-CoA, and finally to a shortened acyl-CoA with the release of acetyl-CoA via thiolysis. The enzyme 3-ketoacyl-CoA thiolase cleaves the beta-ketoacyl-CoA to yield acetyl-CoA and an acyl-CoA shortened by two carbons. Thus, 3-ketoacyl-CoA species are transient intermediates that drive the iterative shortening of fatty acids. Beta-oxidation also occurs in peroxisomes, where very-long-chain fatty acids are processed and can generate similar beta-ketoacyl-CoA intermediates.

Occurrence and examples

Ketoacyl-CoA compounds can have varying chain lengths, from short to very long. A notable example is acetoacetyl-CoA (3-oxobutanoyl-CoA), formed by condensation of two acetyl-CoA molecules. Other chain-length examples include longer beta-ketoacyl-CoA species produced during the oxidation of longer fatty acids.

Clinical and research relevance

Defects in beta-oxidation enzymes disrupt the production and processing of ketoacyl-CoA intermediates, contributing to metabolic disorders. Studying these intermediates helps in understanding fatty acid oxidation disorders, energy homeostasis, and related metabolic regulation.