EC - Soluble epoxide hydrolase

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IntEnz Enzyme Nomenclature


Accepted name:
soluble epoxide hydrolase
Other names:
epoxide hydrase [ambiguous]
epoxide hydratase [ambiguous]
arene-oxide hydratase [ambiguous]
aryl epoxide hydrase [ambiguous]
trans-stilbene oxide hydrolase
cytosolic epoxide hydrolase
Systematic name:
epoxide hydrolase



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, lipid-phosphate phosphatase [1,2]. Like EC, 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, 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 (leukotriene-A4 hydrolase), EC (hepoxilin-epoxide hydrolase), EC (microsomal epoxide hydrolase), EC (soluble epoxide hydrolase) and EC (cholesterol 5,6-oxide hydrolase) [7].

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Structural data: CSA , EC2PDB
Gene Ontology: GO:0004301
CAS Registry Number: 9048-63-9
UniProtKB/Swiss-Prot: (51) [show] [UniProt]


  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 created 2006 (EC part-incorporated 2006)]