HydroxyacylCoA

Hydroxyacyl-CoA refers to a family of Coenzyme A thioesters in which a hydroxyl group is attached to the beta-carbon of an acyl chain, producing beta-hydroxyacyl-CoA species such as 3-hydroxyacyl-CoA. These intermediates are central to the beta-oxidation pathway used to break down fatty acids for energy. In mitochondria and peroxisomes, a fatty acyl-CoA undergoes cycles of oxidation, hydration, oxidation, and thiolysis. The hydration step, catalyzed by enoyl-CoA hydratase, adds water to the trans-enoyl-CoA to form hydroxyacyl-CoA. The subsequent oxidation by 3-hydroxyacyl-CoA dehydrogenase converts it to 3-ketoacyl-CoA, which is then cleaved by beta-ketothiolase to yield acetyl-CoA and a shortened acyl-CoA, continuing the cycle. Hydroxyacyl-CoA species vary by fatty acid chain length (short-, medium-, long-chain) and may differ in stereochemistry depending on the tissue and enzyme involved.

In metabolism, hydroxyacyl-CoA derivatives feed into energy production through the acetyl-CoA and NADH generated during beta-oxidation, and acetyl-CoA can enter the citric acid cycle or ketogenesis during fasting. Clinically, impaired beta-oxidation enzymes or transport can disrupt hydroxyacyl-CoA metabolism and lead to abnormal acyl-CoA or acylcarnitine profiles used in diagnosing fatty acid oxidation disorders.