Seh

Soluble epoxide hydrolase (sEH) is an enzyme that catalyzes the hydrolysis of epoxides to their corresponding vicinal diols. In humans, it is encoded by the EPHX2 gene and is a bifunctional cytosolic protein consisting of an N-terminal lipid phosphatase–like domain and a C-terminal epoxide hydrolase domain, the latter responsible for the epoxide hydrolase activity. sEH metabolizes endogenous epoxides derived from fatty acids, including epoxyeicosatrienoic acids (EETs) from arachidonic acid, and other fatty acid epoxides.

By hydrolyzing epoxides such as EETs, sEH modulates signaling pathways that regulate vascular tone, inflammation and nociception. EETs generally promote vasodilation, anti-inflammatory effects and have protective roles in the nervous system; sEH activity diminishes these signals by converting EETs to less active diols. Consequently, inhibition of sEH tends to elevate tissue levels of epoxides, producing vasodilatory, anti-inflammatory and analgesic effects in various preclinical models.

sEH is broadly expressed, with notable levels in the liver, kidney, brain and vascular tissues. Besides its metabolic role, genetic variations in EPHX2 can influence enzyme activity and have been studied for associations with cardiovascular and metabolic traits, though findings are not uniform across populations.

Therapeutically, potent and selective sEH inhibitors have been developed and studied in preclinical and early clinical settings for hypertension, inflammatory disorders and pain, as well as for potential neuroprotection after brain injury. Ongoing research aims to translate these findings into approved therapies.

See also: epoxide hydrolases, EPHX2.