Enoyl-CoA hydratase, mitochondrial (ECHS1) (ECHS1)

Enoyl-CoA hydratase, mitochondrial (ECHS1), also known as methacrylyl-CoA hydratase, is a critical mitochondrial matrix enzyme involved in the second step of fatty acid beta-oxidation and the catabolism of branched-chain amino acids, particularly valine [1, 2, 4]. It catalyzes the hydration of various short- and medium-chain enoyl-CoA thioesters, such as the conversion of methacrylyl-CoA to 3-hydroxyisobutyryl-CoA [1, 3]. Genetic mutations leading to ECHS1 deficiency result in a severe metabolic disorder characterized by Leigh-like syndrome, neurodegeneration, and the accumulation of toxic, reactive intermediates like methacrylyl-CoA [3, 4, 22]. These intermediates are highly electrophilic and can form covalent adducts with protein sulfhydryl groups, leading to protein cysteine S-2-carboxypropylation and the disruption of the mitochondrial respiratory chain [4, 29]. Beyond its role in rare genetic diseases, ECHS1 is increasingly recognized as a potential therapeutic target in oncology, where its expression is often dysregulated to support metabolic reprogramming and oncogenic mTOR signaling [7, 15, 23]. Preclinical studies have explored small-molecule inhibitors and gene replacement therapies to modulate its activity in cancer and metabolic disorders [15, 24].

Other names

Methacrylyl-CoA hydrataseShort-chain enoyl-CoA hydrataseSCEHEnoyl-CoA hydratase 1mECHmECH1Crotonase

Hydration of trans-2-enoyl-CoA species to 3-hydroxyacyl-CoA