Epoxide hydrolase polymorphisms

Nassar AEF, Talaat RE (2004) Strategies for dealing with metabolite elucidation in drug discovery and development. Drug Discovery Today 9 317-327 Omiecinski CJ, Hassett C, Hosagrahara V (2000) Epoxide hydrolase-polymorphism and role in toxicology. Toxicol Lett 112-113 365-370... 

Omiecinski, C. J., Hassett, C., Hosagrahara, V. (2000). Epoxide hydrolase—polymorphism and role in toxicology. Toxicology letters, 112-113, 365-370. 

Dreisbaeh AW, Japa S, Sigel A, Parent MB, Hess AE, Srinouanprachanh SL, Rettie AE, Kim H, Fa-rin FM, Hamm LL, Lertora JJ (2005) The preva-lenee of CYP2C8, 2C9, 2J2, and soluble epoxide hydrolase polymorphisms in Afriean Americans with hypertension. Am J Hypertens 18 1276-1281... 

L. W. Wormhoudt, J. N. Commandeur, N. P. Vermeulen, Genetic Polymorphisms of Human V-Acetyltransferase, Cytochrome P450, Glutathione 5-Transferase, and Epoxide Hydrolase Enzymes Relevance to Xenobiotic Metabolism and Toxicity , Crit. Rev. Toxicol. 1999, 29, 59 - 124. 

J. G. Hengstler, M. Arand, M. E. Herrero, F. Oesch, Polymorphism of A-Acetyltransfe-rase, Glutathione S-Transferases, Microsomal Epoxide Hydrolase and Sulfotransferase Influence on Cancer Susceptibility , Recent Results Cancer Res. 1998, 154, 47 - 85. 

Other metabolic enzymes that show polymorphic differences in that they can occur as genetic high-activity and low-activity variants include acetylcholinesterase, butyrylcholinesterases, flavin-dependent monooxygenase, alcohol dehydrogenase, epoxide hydrolase, and arylesterase (Beltoft et al. 2001). 

Thomas H, Timms CW, Oesch F. Epoxide hydrolases molecular properties, induction, polymorphisms and function. In Ruckpaul K, Rein H, eds. Frontiers of Bio transformation. Vol. II. Principles, Mechanisms and Biological Consequences of Induction. London Taylor Francis, 1990. 

Many other significant polymorphisms in xenobiotic metabolizing enzymes have been described, including those for several CYP genes, alcohol and aldehyde dehydrogenases, epoxide hydrolase, and paraoxonase. One interesting polymorphism affecting... 

Gupta RC, Atul BV (2000) Drug metabolism studies in animal models. Ind 1 Pharmacol 32 S62-S66 Hassett C, Lin 1, Carty CL et al. (1997) Human hepatic microsomal epoxide hydrolase comparative analysis of polymorphic expression. Arch Biochem Biophys 337 275-283 Hengstler 1G, Arand M, Herrero ME, Oesch F (1998) Polymorphisms of N-acetyltransferases, glutathione S-transferases, microsomal epoxide hydrolase and sulfo-transferases influence on cancer susceptibility. Recent Results Cancer Res 154 47-85... 

Srivastava PK, Sharma VK, Kalonia DS, Grant DF (2004) Polymorphisms in human soluble epoxide hydrolase effects on enzyme activity, enzyme stability, and quaternary structure. Arch Biochem Biophys 427 164-169... 

Wormhoudt LW, Commandeur JN, Vermeulen NP (1999) Genetic polymorphisms of human N-acetyltransferase, cytochrome P450, glutathione-S-transferase, and epoxide hydrolase enzymes relevance to xenobiotic metabolism and toxicity. Crit Rev Toxicol 29 59-124... 

Hengstler JG, Arand M, Herrero ME, Oesch F. Polymorphisms of N-acetyltransferases, glutathione S-transferases, microsomal epoxide hydrolase and sulfo-transferases Influence on cancer susceptibility. Recent Results Cancer Res 1998 154 47-85. 

Figure 43-1 I Schematic view of the role of NAT enzymes in the metabolism of aromatic amines. N-acetylation might be a detoxification reaction in a number of cases however, after N-hydroxylation of aromatic amines (e.g., by CYP enzymes), NAT enzymes can bioactivate these intermediates by either 0-acetylation or intramolecular N,0-acety transfer, leading to the formation of nitrenium ions, which might react with DNA or alternatively be detoxified by, for example, GST enzymes. Importantly, it is shown that a number of other biotransformation enzymes are also involved in the metabolism of aromatic amines as well. (Redrawn from Wormhoudt LW, Commandeur jNM, Vermeuien NPE. Genetic polymorphisms of human N-acetyitransferase, cytochrome P450, glutathione-S-transferase, and epoxide hydrolase enzymes relevance to xenobiotic metabolism and toxicity. Crit Rev Toxicol 1999 29 59-124. Reproduced by permission from Taylor and Francis, Inc.)...

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