Microsomal epoxide hydrolase (mEH)

Microsomal epoxide hydrolase (mEH), encoded by the EPHX1 gene, is a critical biotransformation enzyme primarily localized to the endoplasmic reticulum of hepatocytes and other tissues (UniProt P07099). It plays a dual role in the metabolism of xenobiotics, typically detoxifying reactive epoxides into more soluble dihydrodiols, though it can also bioactivate certain procarcinogens, such as polycyclic aromatic hydrocarbons, into highly toxic metabolites (Václavíková et al., 2015; PubMed: 26216302). Beyond its role in drug metabolism, mEH functions as a sodium-dependent transporter for bile acids and participates in the regulation of endogenous signaling lipids, such as epoxyeicosatrienoic acids (EETs) and endocannabinoids (PubMed: 22798687, 24958911). Genetic variations in the EPHX1 gene, particularly the Tyr113His and His139Arg polymorphisms, significantly influence enzyme activity and have been linked to susceptibility to various cancers, chronic obstructive pulmonary disease (COPD), and preeclampsia (GeneCards; Wikipedia). While mEH is a major site for drug-drug interactions involving anticonvulsants like carbamazepine and phenytoin, it is also being explored as a therapeutic target (PubMed: 25810095). Specifically, dual inhibition of mEH and soluble epoxide hydrolase (sEH) is investigated as a strategy to treat cardiovascular and inflammatory diseases by elevating protective lipid mediators (PubMed: 25810095).

Other names

EPHX1Epoxide hydrolase 1Epoxide hydrataseMicrosomal epoxide hydrataseEPOXHYL1

Inhibition of epoxide hydrolase activity to modulate the levels of reactive epoxide metabolites or signaling lipids (PubMed: 25810095); induction of enzyme expression to enhance detoxification of xenobiotics (PubMed: 26216302).