Cholesterol epoxide hydrolase

Cholesterol epoxide hydrolase, which is expressed in the endoplasmic reticulum and catalyzes the trans-addition of H20 to cholesterol 5,6a-ox-ide and cholesterol 5,6/3-oxide, as well as to a number of other steroid 5,6-oxides. The products are the corresponding vicinal diols [54][55],... 

From the above, it is clear that the epoxide hydrolases of greatest significance in drug and xenobiotic metabolism are the microsomal and soluble ones. Their catalytic mechanism, which we now examine, is different from that of cholesterol epoxide hydrolase and LTA4 hydrolase (e.g., [57][58]). 

F. Muller, M. Arand, H. Frank, A. Seidel, W. Hinz, L. Winkler, K. Hanel, E. Blee, J. K. Beetham, B. D. Hammock, F. Oesch, Visualization of a Covalent Intermediate Between Microsomal Epoxide Hydrolase, but not Cholesterol Epoxide Hydrolase, and Their Substrates , Eur. J. Biochem. 1997, 245, 490 - 496. 

So far five different types of epoxide hydrolases have been characterized in mammals, and they have been grouped depending on their enzymatic activity and biochemical characteristics. These groups include the soluble epoxide hydrolases (sEHs, also referred to as cytosolic epoxide hydrolases) [50], microsomal epoxide hydrolases (mEHs) [34], leukotriene A4 hydrolase (LTA44H) [51], cholesterol epoxide hydrolase [52], and hepoxilin hydrolase [53]. Several reviews have focused on these enzymes of medical importance [34,54]. 

W. Levin, D. P. Michaud, P. E. Thomas, D. M. Jerina, Distinct Rat Hepatic Microsomal Epoxide Hydrolases Catalyze the Hydration of Cholesterol 5,6a-Oxide and Certain Xenobiotic Alkene and Arene Oxides , Arch. Biochem. Biophys. 1983, 220, 485 - 494. 

A second unique microsomal epoxide hydrolases has been described. This enzyme appears to have a narrow substrate specificity, being specific for cholesterol 5,6-oxides and related steroid 5,6-oxides. 

The epoxide hydrolases are very important enzymes that render the epoxides formed by CYP enzymes harmless. Mammals have three distinct epoxide hydrolases. One microsomal form is specific for cholesterol-5,6a-oxide. It is induced by the same substances that induce the CYP enzymes. Another, less specific epoxide hydrolase is located in the endoplasmatic reticulum close to the CYP enzymes and is more important for xenobiotic substances. A third type, of some importance, is located in the cytosol. A typical substrate is trans-stilbene oxide, which also is an inducer. Some epoxides, such as diel-drin, are not detoxicated by these enzymes due to steric hindrance, but stilbene epoxide is a good substrate that is frequently used in experimental studies of these enzymes. 

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