||Catalyses the hydrolysis of trans-substituted epoxides, such as trans-stilbene oxide, as well as various aliphatic epoxides derived from fatty-acid metabolism . It is involved in the metabolism of arachidonic epoxides (epoxyicosatrienoic acids; EETs) and linoleic acid epoxides. The EETs, which are endogenous chemical mediators, act at the vascular, renal and cardiac levels to regulate blood pressure [4,5]. The enzyme from mammals is a bifunctional enzyme: the C-terminal domain exhibits epoxide-hydrolase activity and the N-terminal domain has the activity of EC 188.8.131.52, lipid-phosphate phosphatase [1,2]. Like EC 184.108.40.206, microsomal epoxide hydrolase, it is probable that the reaction involves the formation of an hydroxyalkyl—enzyme intermediate [4,6]. The enzyme can also use leukotriene A4, the substrate of EC 220.127.116.11, leukotriene-A4 hydrolase, but it forms 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid rather than leukotriene B4 as the product [9,10]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 18.104.22.168 (leukotriene-A4 hydrolase), EC 22.214.171.124 (hepoxilin-epoxide hydrolase), EC 126.96.36.199 (microsomal epoxide hydrolase), EC 188.8.131.52 (soluble epoxide hydrolase) and EC 184.108.40.206 (cholesterol 5,6-oxide hydrolase) .
||Newman, J.W., Morisseau, C., Harris, T.R. and Hammock, B.D. The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme
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||Cronin, A., Mowbray, S., Dürk, H., Homburg, S., Fleming, I., Fisslthaler, B., Oesch, F. and Arand, M. The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase. Proc. Natl. Acad. Sci. USA 100 (2003) 1552–1557. [PMID: 12574508]
||Oesch, F. Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds. Xenobiotica 3 (1973) 305–340. [PMID: 4584115]
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epoxyeicosatrienoic acids. Circ. Res. 87 (2000) 992–998. [PMID: 11090543]
||Lacourciere, G.M. and Armstrong, R.N. The catalytic mechanism of microsomal epoxide hydrolase involves an ester intermediate. J. Am. Chem. Soc. 115 (1993) 10466.
||Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41–59. [PMID: 11154734]
||Zeldin, D.C., Wei, S., Falck, J.R., Hammock, B.D., Snapper, J.R. and Capdevila, J.H. Metabolism of epoxyeicosatrienoic acids by cytosolic epoxide hydrolase:
substrate structural determinants of asymmetric catalysis. Arch. Biochem. Biophys. 316 (1995) 443–451. [PMID: 7840649]
||Haeggström, J., Meijer, J. and Rådmark, O. Leukotriene A4. Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase. J. Biol. Chem. 261 (1986) 6332–6337. [PMID: 3009453]
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