Epoxide hydrolases (EH's), also known as epoxide hydratases, are enzymes that metabolize compounds that contain an epoxide residue; they convert this residue to two hydroxyl residues through an epoxide hydrolysis reaction to form diol products. Several enzymes possess EH activity. Microsomal epoxide hydrolase (epoxide hydrolase 1, EH1, or mEH), soluble epoxide hydrolase (sEH, epoxide hydrolase 2, EH2, or cytoplasmic epoxide hydrolase), and the more recently discovered but not as yet well defined functionally, epoxide hydrolase 3 (EH3) and epoxide hydrolase 4 (EH4) are structurally closely related isozymes. Other enzymes with epoxide hydrolase activity include leukotriene A4 hydrolase, Cholesterol-5,6-oxide hydrolase, MEST (gene) (Peg1/MEST), and Hepoxilin-epoxide hydrolase. The hydrolases are distinguished from each other by their substrate preferences and, directly related to this, their functions. Epoxide hydrolase types mEH (EH1), sEH (EH2), EH3, and EH4 isozymes Humans express four epoxide hydrolase isozymes: mEH, sEH, EH3, and EH4. These isozymes are known (mEH and sEH) or presumed (EH3 and EH4) to share a common structure that includes containing an Alpha/beta hydrolase fold and a common reaction mechanism wherein they add water to epoxides to form vicinal cis (see (cis-trans isomerism); see (epoxide#Olefin oxidation using organic peroxides and metal catalysts)) diol products. They differ, however, in subcellular location, substrate preferences, tissue expression, and/or function. mEH mEH is widely expressed in virtually all mammalian cells as an endoplasmic reticulum-bound (i.e. microsomal-bound) enzyme with its C terminal catalytic domain facing the cytoplasm; in some tissues, however, mEH has been found bound to the cell surface plasma membrane with its catalytic domain facing the extracellular space. The primary function of mEH is to convert potentially toxic xenobiotics and other compounds that possess epoxide residues (which is often due to their initial metabolism by cytochrome P450 enzymes to epoxides) to diols. Epoxides are highly reactive electrophilic compounds that form adducts with DNA and proteins and also cause strand breaks in DHA; in consequence, epoxides can cause gene mutations, cancer, and the inactivation of critical proteins. The diols thereby formed are usually not toxic or far less toxic than their epoxide predecessors, are readily further metabolized, and ultimately excreted in the urine. mEH also metabolizes certain epoxides of polyunsaturated fatty acids such as the epoxyeicosatrienoic acids (EETs) but its activity in doing this is far less than that of sEH; mEH therefore may play a minor role, compared to sEH, in limiting the bioactivity of these cell signaling compounds