Hydrolases;
Acting on ether bonds;
Ether hydrolases
BRITE hierarchy

cis-stilbene-oxide hydrolase

(1) cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol [RN:R07627];
(2) 1-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]methanamine + H2O = 2-({[(4-methoxyphenyl)methyl](methyl)amino}methyl)-2-methylpropane-1,3-diol [RN:R11930]

R07627 R11930;
(other) R07013 R07014 R07027 R07071 R07072 R07082 R09410 R09417 R09443
Reaction

cis-stilbene oxide [CPD:C16014];
H2O [CPD:C00001];
1-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]methanamine [CPD:C21775]

This is a key hepatic enzyme that catalyses the hydrolytic ring opening of oxiranes (epoxides) and oxetanes to give the corresponding diols. The enzyme is involved in the metabolism of numerous substrates including the stereoselective hydrolytic ring opening of 7-oxabicyclo[4.1.0]hepta-2,4-dienes (arene oxides) to the corresponding trans-dihydrodiols. The reaction proceeds via a triad mechanism and involves the formation of an hydroxyalkyl-enzyme intermediate. Five epoxide-hydrolase enzymes have been identified in vertebrates 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).

EC 3.3.2.9 created 2006 (EC 3.3.2.3 created 1978, modified 1999, part incorporated 2006), modified 2017

1  [PMID:4998715]

Oesch F, Daly J.

Solubilization, purification, and properties of a hepatic epoxide hydrase.

Biochim Biophys Acta 227:692-7 (1971)
DOI:10.1016/0005-2744(71)90018-0

2

Jakoby, W.B. and Fjellstedt, T.A.

Epoxidases.

In: Boyer, P.D. (Ed.), The Enzymes, 3rd ed., vol. 7, Academic Press, New York, 1972, p. 199-212.

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 3:305-40 (1973)
DOI:10.3109/00498257309151525

4  [PMID:4463951]

Oesch F.

Purification and specificity of a human microsomal epoxide hydratase.

Biochem J 139:77-88 (1974)
DOI:10.1042/bj1390077

5  [PMID:240858]

Lu AY, Ryan D, Jerina DM, Daly JW, Levin W.

Liver microsomal expoxide hydrase. Solubilization, purification, and characterization.

J Biol Chem 250:8283-8 (1975)

6  [PMID:7986671]

Bellucci G, Chiappe C, Ingrosso G.

Kinetics and stereochemistry of the microsomal epoxide hydrolase-catalyzed hydrolysis of cis-stilbene oxides.

Chirality 6:577-82 (1994)
DOI:10.1002/chir.530060711

7  [PMID:11154734]

Fretland AJ, Omiecinski CJ.

Epoxide hydrolases: biochemistry and molecular biology.

Chem Biol Interact 129:41-59 (2000)
DOI:10.1016/S0009-2797(00)00197-6

8  [PMID:15822179]

Morisseau C, Hammock BD.

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

Annu Rev Pharmacol Toxicol 45:311-33 (2005)
DOI:10.1146/annurev.pharmtox.45.120403.095920

9  [PMID:15748653]

Newman JW, Morisseau C, Hammock BD.

Epoxide hydrolases: their roles and interactions with lipid metabolism.

Prog Lipid Res 44:1-51 (2005)
DOI:10.1016/j.plipres.2004.10.001

10 [PMID:28600384]

Toselli F, Fredenwall M, Svensson P, Li XQ, Johansson A, Weidolf L, Hayes MA

Oxetane Substrates of Human Microsomal Epoxide Hydrolase.

Drug Metab Dispos 45:966-973 (2017)
DOI:10.1124/dmd.117.076489