KEGG   ENZYME: 3.3.2.9Help
Entry
EC 3.3.2.9                  Enzyme                                 

Name
microsomal epoxide hydrolase;
microsomal oxirane/oxetane hydrolase;
epoxide hydratase (ambiguous);
microsomal epoxide hydratase (ambiguous);
epoxide hydrase;
microsomal epoxide hydrase;
arene-oxide hydratase (ambiguous);
benzo[a]pyrene-4,5-oxide hydratase;
benzo(a)pyrene-4,5-epoxide hydratase;
aryl epoxide hydrase (ambiguous);
cis-epoxide hydrolase;
mEH;
EPHX1 (gene name)
Class
Hydrolases;
Acting on ether bonds;
Ether hydrolases
BRITE hierarchy
Sysname
cis-stilbene-oxide hydrolase
Reaction(IUBMB)
(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]
Reaction(KEGG)
Substrate
cis-stilbene oxide [CPD:C16014];
H2O [CPD:C00001];
1-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]methanamine [CPD:C21775]
Product
(1R,2R)-1,2-diphenylethane-1,2-diol;
2-({[(4-methoxyphenyl)methyl](methyl)amino}methyl)-2-methylpropane-1,3-diol [CPD:C21776]
Comment
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).
History
EC 3.3.2.9 created 2006 (EC 3.3.2.3 created 1978, modified 1999, part incorporated 2006), modified 2017
Pathway
ec00980  Metabolism of xenobiotics by cytochrome P450
Orthology
K01253  microsomal epoxide hydrolase
Genes
HSA: 2052(EPHX1)
PTR: 457777(EPHX1)
PPS: 100995858(EPHX1)
GGO: 101130068(EPHX1)
PON: 100173792(EPHX1)
NLE: 100592261
MCC: 700180(EPHX1)
MCF: 101866419(EPHX1)
CSAB: 103230002(EPHX1)
RRO: 104660094
RBB: 108538734(EPHX1)
CJC: 100409580(EPHX1)
SBQ: 101029266(EPHX1)
MMU: 13849(Ephx1)
RNO: 25315(Ephx1)
CGE: 100758590
HGL: 101725522(Ephx1)
CCAN: 109691483
OCU: 100009104(EPHX1)
TUP: 102495357(EPHX1)
CFA: 480113(EPHX1)
AML: 100477671(EPHX1)
UMR: 103669061(EPHX1)
ORO: 101368385(EPHX1)
FCA: 101085519(EPHX1)
PTG: 102949568(EPHX1)
AJU: 106968617(EPHX1)
BTA: 535293(EPHX1)
BOM: 102267623(EPHX1)
BIU: 109570425(EPHX1)
PHD: 102316040(EPHX1)
CHX: 100860945(EPHX1)
OAS: 101111038(EPHX1)
SSC: 397639(EPHX1)
CFR: 102519415(EPHX1)
CDK: 105099693(EPHX1)
BACU: 103003233(EPHX1)
LVE: 103074317(EPHX1)
OOR: 101288139(EPHX1)
ECB: 100054269(EPHX1)
EPZ: 103543505(EPHX1)
EAI: 106844729(EPHX1)
MYB: 102263401(EPHX1)
MYD: 102767193(EPHX1)
HAI: 109391461(EPHX1)
RSS: 109446996(EPHX1)
PALE: 102883919(EPHX1)
LAV: 100673770(EPHX1)
TMU: 101360751
MDO: 100025778(EPHX1)
SHR: 100925093(EPHX1)
OAA: 100081956(EPHX1)
GGA: 421321(EPHX1) 421447(EPHX1L)
MGP: 100539493 100545721(EPHX1)
CJO: 107311037(EPHX1) 107311272
APLA: 101790722 101801005(EPHX1)
ACYG: 106031535(EPHX1)
TGU: 100222959(EPHX1) 100227392
GFR: 102041759(EPHX1) 102042334
FAB: 101806940(EPHX1) 101814529
PHI: 102100615 102109472(EPHX1)
PMAJ: 107201817(EPHX1)
CCW: 104684354 104685565(EPHX1)
FPG: 101912868 101914944(EPHX1)
FCH: 102050687 102059804(EPHX1)
CLV: 102085632(EPHX1) 102092641
AAM: 106482713(EPHX1) 106485556
ASN: 102368835(EPHX1) 102386213
AMJ: 102571832 102577262(EPHX1)
PSS: 102456152 102457257(EPHX1)
CMY: 102934448(EPHX1) 102942209
CPIC: 101936865(EPHX1) 101949762
ACS: 100554472 100555586(ephx1)
PVT: 110075401(EPHX1)
PBI: 103058096(EPHX1)
GJA: 107119060(EPHX1)
XLA: 108716563 432100(ephx1.L)
XTR: 100158543(ephx1)
NPR: 108787057(EPHX1)
DRE: 394043(ephx1)
SRX: 107732537
SANH: 107690044(ephx1)
SGH: 107601524
CCAR: 109080243
IPU: 108263372(ephx1)
AMEX: 103040834(ephx1)
TRU: 101066103(ephx1)
LCO: 104918259 104918311(ephx1)
NCC: 104963447(ephx1)
MZE: 101463752 101487605(ephx1)
OLA: 101166982 101172051(ephx1)
XMA: 102229129 102230310(ephx1)
PRET: 103477226
CSEM: 103380678(ephx1)
LCF: 108901766(ephx1)
HCQ: 109516170
BPEC: 110154206(ephx1)
ELS: 105017773(ephx1)
SFM: 108925178(ephx1)
LCM: 102353239(EPHX1)
CMK: 103181611
CIN: 100176449
SPU: 588166
APLC: 110978249
SKO: 100371948
CEL: CELE_W01A11.1(W01A11.1)
CBR: CBG18950
BMY: Bm1_48070
TSP: Tsp_04403
LAK: 106154062
EPA: 110242247
PIC: PICST_38202(SEH1)
ANI: AN3017.2
ANG: ANI_1_312144(An16g02170)
CNE: CNN02220
HNE: HNE_2052
PUB: SAR11_0803(ephX1)
BCL: ABC1387
MBB: BCG_1185(ephC) BCG_1977(ephB) BCG_3200c(mesTb) BCG_3201c(mesTa) BCG_3728(ephE)
 » show all
Taxonomy
Reference
1  [PMID:4998715]
  Authors
Oesch F, Daly J.
  Title
Solubilization, purification, and properties of a hepatic epoxide hydrase.
  Journal
Biochim. Biophys. Acta. 227 (1971) 692-7.
Reference
2
  Authors
Jakoby, W.B. and Fjellstedt, T.A.
  Title
Epoxidases.
  Journal
In: Boyer, P.D. (Ed.), The Enzymes, 3rd ed., vol. 7, Academic Press, New York, 1972, p. 199-212.
Reference
3  [PMID:4584115]
  Authors
Oesch F.
  Title
Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds.
  Journal
Xenobiotica. 3 (1973) 305-40.
Reference
4  [PMID:4463951]
  Authors
Oesch F.
  Title
Purification and specificity of a human microsomal epoxide hydratase.
  Journal
Biochem. J. 139 (1974) 77-88.
Reference
5  [PMID:240858]
  Authors
Lu AY, Ryan D, Jerina DM, Daly JW, Levin W.
  Title
Liver microsomal expoxide hydrase. Solubilization, purification, and characterization.
  Journal
J. Biol. Chem. 250 (1975) 8283-8.
Reference
6  [PMID:7986671]
  Authors
Bellucci G, Chiappe C, Ingrosso G.
  Title
Kinetics and stereochemistry of the microsomal epoxide hydrolase-catalyzed hydrolysis of cis-stilbene oxides.
  Journal
Chirality. 6 (1994) 577-82.
Reference
7  [PMID:11154734]
  Authors
Fretland AJ, Omiecinski CJ.
  Title
Epoxide hydrolases: biochemistry and molecular biology.
  Journal
Chem. Biol. Interact. 129 (2000) 41-59.
Reference
8  [PMID:15822179]
  Authors
Morisseau C, Hammock BD.
  Title
Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles.
  Journal
Annu. Rev. Pharmacol. Toxicol. 45 (2005) 311-33.
Reference
9  [PMID:15748653]
  Authors
Newman JW, Morisseau C, Hammock BD.
  Title
Epoxide hydrolases: their roles and interactions with lipid metabolism.
  Journal
Prog. Lipid. Res. 44 (2005) 1-51.
Reference
10 [PMID:28600384]
  Authors
Toselli F, Fredenwall M, Svensson P, Li XQ, Johansson A, Weidolf L, Hayes MA
  Title
Oxetane Substrates of Human Microsomal Epoxide Hydrolase.
  Journal
Drug. Metab. Dispos. 45 (2017) 966-973.
Other DBs
ExplorEnz - The Enzyme Database: 3.3.2.9
IUBMB Enzyme Nomenclature: 3.3.2.9
ExPASy - ENZYME nomenclature database: 3.3.2.9
BRENDA, the Enzyme Database: 3.3.2.9

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