soluble epoxide hydrolase / lipid-phosphate phosphatase [EC:3.3.2.10 3.1.3.76]

PMID:12574510

Newman JW, Morisseau C, Harris TR, Hammock BD

The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity.

Proc Natl Acad Sci U S A 100:1558-63 (2003)
DOI:10.1073/pnas.0437724100

[hsa:2053]

Hydrolases;
Acting on ether bonds;
Ether hydrolases

epoxide hydrolase

an epoxide + H2O = a glycol [RN:R02822]

R02822 > R05842 R07108 R07109 R07110 R07111

epoxide [CPD:C00722];
H2O [CPD:C00001]

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 (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 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-icosatetraenoic 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].

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

1  [PMID:12574510]

Newman JW, Morisseau C, Harris TR, Hammock BD.

The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity.

Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 1558-63.

[hsa:2053]

2  [PMID:12574508]

Cronin A, Mowbray S, Durk H, Homburg S, Fleming I, Fisslthaler B, Oesch F, Arand M.

The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase.

Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 1552-7.

[hsa:2053] [rno:65030]

3  [PMID:4584115]

Oesch F.

Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds.

Xenobiotica. 3 (1973) 305-40.

4  [PMID:15822179]

Morisseau C, Hammock BD.

Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles.

Annu. Rev. Pharmacol. Toxicol. 45 (2005) 311-33.

5  [PMID:11090543]

Yu Z, Xu F, Huse LM, Morisseau C, Draper AJ, Newman JW, Parker C, Graham L, Engler MM, Hammock BD, Zeldin DC, Kroetz DL.

Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids.

Circ. Res. 87 (2000) 992-8.

6

Lacourciere, G.M. and Armstrong, R.N.

The catalytic mechanism of microsomal epoxide hydrolase involves an ester intermediate.

J. Am. Chem. Soc. 115 (1993) 10466-10456.

7  [PMID:11154734]

Fretland AJ, Omiecinski CJ.

Epoxide hydrolases: biochemistry and molecular biology.

Chem. Biol. Interact. 129 (2000) 41-59.

8  [PMID:7840649]

Zeldin DC, Wei S, Falck JR, Hammock BD, Snapper JR, Capdevila JH.

Metabolism of epoxyeicosatrienoic acids by cytosolic epoxide hydrolase: substrate structural determinants of asymmetric catalysis.

Arch. Biochem. Biophys. 316 (1995) 443-51.

9  [PMID:3009453]

Haeggstrom J, Meijer J, Radmark 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) 6332-7.

10 [PMID:15748653]

Newman JW, Morisseau C, Hammock BD.

Epoxide hydrolases: their roles and interactions with lipid metabolism.

Prog. Lipid. Res. 44 (2005) 1-51.