Epoxide hydrolase 2

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme that in humans is encoded by the EPHX2 gene. sEH is a member of the epoxide hydrolase family. This enzyme, found in both the cytosol and peroxisomes, binds to specific epoxides and converts them to the corresponding diols. A different region of this protein also has lipid-phosphate phosphatase activity. Mutations in the EPHX2 gene have been associated with familial hypercholesterolemia.

Tissue distribution

While most highly expressed in the liver, sEH is also expressed in other tissues including vascular endothelium, leukocytes, red blood cells, smooth muscle cells, adipocytes and the kidney proximal tubule.

Catalyzed reactions

The form of sEH in the intracellular environment is a homodimer with two distinct activities in two separate structural domains of each monomer: the C-terminal epoxide hydrolase activity (soluble epoxide hydrolase: EC 3.3.2.10) and the N-terminal phosphatase activity (lipid-phosphate phosphatase: EC 3.1.3.76). sEH converts epoxides, or three membered cyclic ethers, to their corresponding diols through the addition of a molecule of water. The resulting diols are more water-soluble than the parent epoxides, and so are more readily excreted by the organism.

EPHX1

Epoxide hydrolase 1 is an enzyme encoded by the EPHX1 gene in humans.

Function

Epoxide hydrolase plays an important role in both the activation and detoxification of exogenous chemicals such as polycyclic aromatic hydrocarbons.

Discovery

Microsomal epoxide hydrolase 1 (EPHX1) was first isolated by Watabe and Kanehira from rabbit liver and later also purified from human liver and characterized. EPHX1 belongs to the family of α/β hydrolases and converts epoxides to diols.

Tissue distribution

EPHX1 protein can be found predominantly in membrane fraction of the endoplasmic reticulum of eucaryotic cells. Its expression in mammals is generally the highest in the liver, followed by adrenal gland, lung, kidney, lung, and intestine. It was found also in bronchial epithelial cells and upper gastrointestinal tract. EPHX1 expression is individually variable among humans and it can be modestly induced by chemicals as phenobarbital, β-naphtoflavone, benzanthracene, trans-stilbene oxide, etc.