Enoyl-CoA hydratase and related fatty acid metabolism enzymes (ECH)

Enoyl-CoA hydratase and related fatty acid metabolism enzymes constitute a group of proteins, primarily within the crotonase superfamily, that are essential for the breakdown of fatty acids and branched-chain amino acids. These enzymes, including mitochondrial short-chain enoyl-CoA hydratase (ECHS1) and peroxisomal enoyl-CoA hydratase (ECH1), catalyze the second step of the beta-oxidation cycle: the hydration of alpha,beta-unsaturated enoyl-CoA thioesters to form beta-hydroxyacyl-CoA. This process is vital for energy production and the maintenance of metabolic homeostasis across various tissues. Genetic mutations in ECHS1 lead to a severe neurometabolic disorder known as ECHS1 deficiency (or Leigh syndrome), characterized by the accumulation of toxic metabolites and impaired mitochondrial function. In oncology, these enzymes are frequently dysregulated and have been identified as potential therapeutic targets in cancers such as acute myeloid leukemia and breast cancer, where they support metabolic reprogramming and chemoresistance. Pharmacological strategies include the use of experimental irreversible inhibitors like methylenecyclopropylformyl-CoA and therapeutic dietary interventions like triheptanoin, which acts as an anaplerotic agent to bypass metabolic blocks.

Other names

CrotonaseEnoyl-CoA hydratase familyShort-chain enoyl-CoA hydratase (ECHS1)Peroxisomal enoyl-CoA hydratase (ECH1)Enoyl-CoA hydratase domain-containing protein (ECHDC)Enoyl-CoA hydratase/isomerase family