Enoyl-CoA hydratase (ECH (also ECHS1 for the human short-chain isoform))

Enoyl-CoA hydratase is a mitochondrial enzyme that catalyzes the reversible hydration of the double bond in enoyl-CoA thioesters during fatty acid β-oxidation, producing 3-hydroxyacyl-CoA. The human short-chain isoform (ECHS1) is vital for the degradation of short- and medium-chain fatty acids and operates at near-diffusion controlled rates. Structurally, it forms a hexamer and employs two catalytic glutamate residues to mediate a syn-addition of water across the substrate double bond. Genetic defects in ECHS1 cause severe mitochondrial disorders, highlighting its critical role in energy homeostasis and human health. Enoyl-CoA hydratase belongs to the crotonase superfamily and is also involved in branched-chain amino acid catabolism in some contexts. There are research-grade inhibitors, but clinically-approved drugs targeting this enzyme are not yet established.

Other names

Crotonase2-enoyl-CoA hydrataseBeta-hydroxyacyl-CoA dehydraseShort-chain enoyl-CoA hydrataseAcyl-CoA hydrataseBeta-hydroxyacid dehydraseD-3-hydroxyacyl-CoA dehydrataseTrans-2-enoyl-CoA hydrataseEnoyl coenzyme A hydrataseShort chain enoyl coenzyme A hydrataseEnoyl hydrase

Competitive inhibition (e.g., substrate analogs bind the active site to block activity). Covalent adduct formation with active site residues leading to irreversible enzyme inactivation. Modulation of catalytic glutamate residues (Glu144, Glu164) which are essential for hydration reaction.