Microsomal epoxide hydrolase (mEH) (mEH)

Microsomal epoxide hydrolase (mEH), encoded by the EPHX1 gene, is a critical biotransformation enzyme primarily localized in the endoplasmic reticulum of the liver and other tissues [1, 2]. It belongs to the alpha/beta-hydrolase fold family and functions by catalyzing the hydrolysis of highly reactive, electrophilic epoxides into less reactive and more water-soluble vicinal diols [1, 5]. While traditionally recognized for its role in detoxifying xenobiotics such as polycyclic aromatic hydrocarbons and anticonvulsant drugs like carbamazepine, mEH can also bioactivate certain pro-carcinogens into more potent toxic intermediates [2, 4]. Beyond xenobiotic metabolism, it plays significant roles in endogenous processes, including bile acid transport, steroid metabolism, and the regulation of lipid mediators like epoxyeicosatrienoic acids (EETs) and endocannabinoids [10, 16]. Genetic polymorphisms in EPHX1, such as the Tyr113His and His139Arg variants, are associated with altered enzyme activity and susceptibility to various diseases, including cancer, COPD, and preeclampsia [1, 6]. Pharmacologically, mEH is a target for inhibitors like valpromide, which can lead to clinically significant drug-drug interactions by slowing the clearance of active drug metabolites [6, 8].

Other names

EPHX1Epoxide hydrataseEpoxide hydraseHYL1Epoxide hydrolase 1Microsomal epoxide hydratase

Inhibition of the hydrolytic conversion of reactive epoxide intermediates into vicinal diols, thereby modulating the balance between metabolic detoxification and the bioactivation of toxic or carcinogenic compounds.