Polycyclic aromatic hydrocarbons epoxide hydrolases

The microsomal epoxide hydrolases (microsomal EH, mEH), predominantly found in the endoplasmic reticulum, regio- and stereoselectively catalyze the hydration of both alkene and arene oxides, including oxides of polycyclic aromatic hydrocarbons. These enzymes have been purified to homogeneity from various species and tissues [22] [41 - 46], The human microsomal EH contains 455 amino acids (Mr 52.5 kDa) and is the product of the EPHX1 gene [47] (also known as HYL1 [48]). 

Together with glutathione conjugation, hydration is a major pathway in the inactivation and detoxification of arene oxides. Exceptions to this rule will be treated when discussing polycyclic aromatic hydrocarbons. Arene oxides are good substrates for microsomal EH, as evidenced in Table 10.1, where hydration of selected arene oxides, alkene oxides, and cy-cloalkene oxides by purified rat liver epoxide hydrolase is compared. The hy- ... 

M. Shou, F. J. Gonzalez, H. V. Gelboin, Stereoselective Epoxidation and Hydration at the K-Region of Polycyclic Aromatic Hydrocarbons by cDNA-Expressed Cytochromes P450 1A1, 1A2, and Epoxide Hydrolase , Biochemistry 1996, 35, 15807 - 15813. 

The primary goal of initial studies of the microsomal and purified epoxide-hydrolase catalyzed hydration of arene oxides of polycyclic aromatic hydrocarbons was an attempt to identify structure-activity relationships. To this end, some selected values for the hydration of a series of arene oxides are given in Table 2. One of the more obvious aspects of this study was that there is no apparent relation-... 

Yang, S. K. (1988). Stereoselectivity of Cytochrome P-450 Isozymes and Epoxide Hydrolase in the Metabolism of Polycyclic Aromatic Hydrocarbons, Biochetn. Pharmacol, 37 61-70. 

Oesch F, Golan M. 1980. Specificity of mouse liver cytosolic epoxide hydrolase for K-region epoxides derived from polycyclic aromatic hydrocarbons. Cancer Lett 9 169-175. 

Yang SK. 1988. Stereoselectivity of cytochrome P-450 isozymes and epoxide hydrolase in the metabolism of polycyclic aromatic hydrocarbons. Biochem Pharmacol 37(1) 61-70. 

Abbreviations PAH, polycyclic aromatic hydrocarbon DE, diol epoxide PAHDE, polycyclic aromatic hydrocarbon diol epoxide PAHTC, polycyclic aromatic hydrocarbon triol carbocation TC, triol carbocation BaP, benzo[a]pyrene BeP, benzo[e]pyrene BA, benz[a]anthracene DBA, dibenz[a,h]anthracene BcPh, benzo[c)phenanthrene Ch, chrysene MCh, methylchrysene MBA, 7-methyl benz[a]anthracene DMBA, 7,12-dimethyl benz[a]anthracene EBA, 7-ethyl benz[a]anthracene DB(a,l)P, dibenzo[a,l]pyrene MSCR, mechanism-based structure-carcinogenicity relationship PMO, Perturbational molecular orbital method dA, deoxyadenosine dC, deoxycytosine dG, deoxyguanosine MOS, monoxygenase enzyme system EH, epoxide hydrolase enzyme system N2(G), exocyclic nitrogen of guanine C, electrophilic centre of PAHTC K, intercalation constant CD, circular dichroism LD, linear dichroism. 

Epoxide Hydrolase. Epoxide hydrolase (EH) activity has been studied in numerous tissues with many different substrates (71-72). Hepatic microsomal EH has been shown to be induced by polycyclic aromatic hydrocarbons, but is insensitive to cytochrome P-450 type inducers (73). Epoxide hydrolase has been related to the activation of polycyclic aromatic hydrocarbons into reactive carcinogens (70). Epoxide hydrolase activity has been determined... 

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