IntEnz

EC 3.3.2.10 - Soluble epoxide hydrolase

IntEnz Enzyme Nomenclature
EC 3.3.2.10

Names

Reaction

• an epoxide + H2O = a glycol

Comments:

Catalyses the hydrolysis of trans-substituted epoxides, such as trans-stilbene oxide, as well as various aliphatic epoxides derived from fatty-acid metabolism [7]. It is involved in the metabolism of arachidonic epoxides (epoxyeicosatrienoic 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 3.1.3.76, lipid-phosphate phosphatase [1,2]. Like EC 3.3.2.9, 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 3.3.2.6, leukotriene-A4 hydrolase, but it forms 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid rather than leukotriene B4 as the product [9,10]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol 5,6-oxide hydrolase) [7].

Links to other databases

References

1. Newman, J.W., Morisseau, C., Harris, T.R. and Hammock, B.D.
   The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity.
   Proc. Natl. Acad. Sci. USA 100 : 1558-1563 (2003). [PMID: 12574510]
2. Cronin, A., Mowbray, S., Durk, 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 : 1552-1557 (2003). [PMID: 12574508]
3. Oesch, F.
   Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds.
   Xenobiotica 3 : 305-340 (1973). [PMID: 4584115]
4. Morisseau, C. and Hammock, B. D.
   Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles.
   Annu. Rev. Pharmacol. Toxicol. 45 : 311-333 (2005). [PMID: 15822179]
5. Yu, Z., Xu, F., Huse, L.M., Morisseau, C., Draper, A.J., Newman, J.W., Parker, C., Graham, L., Engler, M.M., Hammock, B.D., Zeldin, D.C. and Kroetz, D.L.
   Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids.
   Circ. Res. 87 : 992-998 (2000). [PMID: 11090543]
6. Lacourciere, G.M. and Armstrong, R.N.
   The catalytic mechanism of microsomal epoxide hydrolase involves an ester intermediate.
   J. Am. Chem. Soc. 115 : 10466-10456 (1993).
7. Fretland, A.J. and Omiecinski, C.J.
   Epoxide hydrolases: biochemistry and molecular biology.
   Chem. Biol. Interact. 129 : 41-59 (2000). [PMID: 11154734]
8. 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 : 443-451 (1995). [PMID: 7840649]
9. 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 : 6332-6337 (1986). [PMID: 3009453]
10. Newman, J.W., Morisseau, C. and Hammock, B.D.
    Epoxide hydrolases: their roles and interactions with lipid metabolism.
    Prog. Lipid Res. 44 : 1-51 (2005). [PMID: 15748653]

[EC 3.3.2.10 created 2006 (EC 3.3.2.3 part-incorporated 2006)]