EnoylCoAHydratase

Enoyl-CoA hydratase, also known as enoyl-CoA hydratase or crotonase, is an enzyme in the mitochondrial beta-oxidation pathway that hydrates trans-2-enoyl-CoA to L-3-hydroxyacyl-CoA. It functions as part of fatty acid catabolism, helping to shorten long-chain fatty acids by two-carbon units in a cycle that feeds into energy production.

The enzyme catalyzes the hydration of a carbon–carbon double bond, adding water to trans-2-enoyl-CoA to yield the S-configuration of 3-hydroxyacyl-CoA. The reaction proceeds within the active site of a crotonase-family enzyme, a conserved fold that features an active-site catalytic residue, typically a glutamate, that facilitates proton transfer and nucleophilic attack during water addition.

Enoyl-CoA hydratase is commonly located in the mitochondrial matrix in aerobic organisms and is one of several enzymes that orchestrate beta-oxidation. It acts after the initial dehydrogenation of acyl-CoA to trans-2-enoyl-CoA and before the thiolytic cleavage carried out by beta-ketoacyl-CoA thiolase. The enzyme also participates in the metabolism of certain short- and medium-chain enoyl-CoA substrates, reflecting its broader role in fatty acid and energy metabolism.

In humans, the activity is encoded by the ECHS1 gene, which produces a mitochondrial short-chain enoyl-CoA hydratase. Deficiencies in ECHS1 can cause metabolic and neurological disorders, including Leigh-like syndromes, due to impaired valine and fatty acid oxidation and the accumulation of toxic intermediates. Treatment is supportive, with emphasis on metabolic stabilization and supportive care.