KEGG   ENZYME: 3.3.2.9
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
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
HSA2052(EPHX1)
PTR457777(EPHX1)
PPS100995858(EPHX1)
GGO101130068(EPHX1)
PON100173792(EPHX1) 100437687
NLE100592261(EPHX1)
MCC700180(EPHX1)
MCF101866419(EPHX1)
MTHB126937150
CSAB103230002(EPHX1)
CATY105576938(EPHX1)
PANU101012773(EPHX1)
TGE112623225(EPHX1)
RRO104660094(EPHX1)
RBB108538734(EPHX1)
TFN117074936(EPHX1)
PTEH111537082(EPHX1)
CJC100409580(EPHX1)
SBQ101029266(EPHX1)
CSYR103269955(EPHX1)
MMUR105863794(EPHX1)
LCAT123627522(EPHX1)
OGA100943654(EPHX1)
MMU13849(Ephx1)
MCAL110290857(Ephx1)
MPAH110321688(Ephx1)
RNO25315(Ephx1)
MCOC116096986(Ephx1)
MUN110559921(Ephx1)
CGE100750792(Ephx1) 100758590
MAUA101835523 121137159
PLEU114686406
MORG121435840 121435939
MFOT126502146 126502147
AAMP119827559 119828107
NGI103725112 103725113
HGL101725522(Ephx1)
CPOC100721931(Ephx1)
CCAN109691482 109691483
DORD106001117
DSP122102745(Ephx1)
NCAR124961084
OCU100009104(EPHX1)
OPI101530165(EPHX1)
TUP102495357(EPHX1)
CFA480113(EPHX1)
CLUD112648822(EPHX1)
VVP112923564(EPHX1)
VLG121486260(EPHX1)
AML100477671(EPHX1)
UMR103669061(EPHX1)
UAH113262914(EPHX1)
UAR123791844(EPHX1)
ELK111150921
LLV125085943
MPUF106003316(EPHX1)
ORO101368385(EPHX1)
EJU114215601(EPHX1)
ZCA113933305(EPHX1)
MLX118013009(EPHX1)
NSU110571396(EPHX1) 123323815
FCA101085519(EPHX1)
PYU121015164(EPHX1)
PBG122476210(EPHX1)
LRUF124510305
PTG102949568(EPHX1)
PPAD109250808(EPHX1)
AJU106968617(EPHX1)
HHV120234147(EPHX1)
BTA535293(EPHX1)
BOM102267623(EPHX1)
BIU109570425(EPHX1)
BBUB102409402(EPHX1)
CHX100860945(EPHX1)
OAS101111038(EPHX1)
ODA120880347(EPHX1)
CCAD122451836(EPHX1)
SSC397639(EPHX1)
CFR102519415(EPHX1)
CBAI105083879(EPHX1)
CDK105099693(EPHX1)
VPC102527697(EPHX1)
BACU103003233(EPHX1)
LVE103074317(EPHX1)
OOR101288139(EPHX1)
DLE111177519(EPHX1)
PCAD102984566(EPHX1)
PSIU116748723(EPHX1)
ECB100054269(EPHX1)
EPZ103543505(EPHX1)
EAI106844729(EPHX1)
MYB102263401(EPHX1)
MYD102767193(EPHX1)
MMYO118678977(EPHX1)
MNA107543604(EPHX1)
PKL118727632(EPHX1)
HAI109391461(EPHX1)
DRO112318922(EPHX1)
SHON119003202(EPHX1)
AJM119044442(EPHX1)
PDIC114512342(EPHX1)
PHAS123832837(EPHX1)
MMF118640564(EPHX1)
RFQ117018666(EPHX1)
PALE102883919(EPHX1)
PGIG120619125(EPHX1)
PVP105292584(EPHX1)
RAY107517097(EPHX1)
MJV108408993(EPHX1)
TOD119244568(EPHX1)
SARA101537100(EPHX1)
LAV100673770(EPHX1)
TMU101360751
DNM101418215(EPHX1)
MDO100025778(EPHX1)
GAS123245662(EPHX1)
SHR100925093(EPHX1)
PCW110205523(EPHX1)
OAA100081956(EPHX1)
GGA421321(EPHX1) 421447(EPHX1L)
PCOC116229249 116231009(EPHX1)
MGP100539493 100545721(EPHX1)
CJO107311037(EPHX1) 107311272
NMEL110395399(EPHX1) 110396838
APLA101790722 101801005(EPHX1)
ACYG106031535(EPHX1)
AFUL116487216(EPHX1) 116487912
TGU100222959(EPHX1) 100227392
LSR110477509(EPHX1) 110477916
SCAN103817382 103819288(EPHX1)
PMOA120505979(EPHX1) 120506812
OTC121335741 121346931(EPHX1)
PRUF121357056(EPHX1) 121358526
GFR102041759(EPHX1) 102042334
FAB101806940(EPHX1) 101814529
PHI102100615 102109472(EPHX1)
PMAJ107201686 107201817(EPHX1)
CCAE111926266(EPHX1) 111926954
CCW104684354 104685565(EPHX1)
CBRC103612689(EPHX1) 103624121
ETL114059335 114073697(EPHX1)
ZAB102060438 102070896(EPHX1)
ACHL103799966(EPHX1)
FPG101912868 101914944(EPHX1)
FCH102050687 102059804(EPHX1)
CLV102085632(EPHX1) 102092641
EGZ104134609(EPHX1)
NNI104019274(EPHX1)
PLET104618973(EPHX1) 104619723
PCRI104024981 104031194(EPHX1)
ACUN113478105(EPHX1)
TALA104363663 104368663(EPHX1)
PADL103925015(EPHX1)
AFOR103898883(EPHX1) 103902677
ACHC115349892(EPHX1) 115350316
HALD104314305 104325460(EPHX1)
CCRI104161930(EPHX1) 104164844
CSTI104553225(EPHX1) 104557585
EHS104512259 104514942
CMAC104481879(EPHX1) 104486566
MUI104547407
FGA104070751 104073957(EPHX1)
GSTE104259295(EPHX1)
LDI104348936(EPHX1) 104350292
MNB103775848 103777511(EPHX1)
OHA104329296 104331963(EPHX1)
NNT104405042(EPHX1) 104406829
DPUB104299949 104300896(EPHX1)
PGUU104458493(EPHX1) 104459025
ACAR104518807 104527715
AVIT104267999(EPHX1) 104268224
CVF104282324 104294655(EPHX1)
AAM106482713(EPHX1) 106485556
AROW112963396(EPHX1) 112973398
NPD112942790(EPHX1) 112957521
TGT104578955(EPHX1)
DNE112980038(EPHX1) 112997146
SCAM104151569(EPHX1) 104151692
ASN102368835(EPHX1) 102386213
AMJ102571832 102577262(EPHX1)
CPOO109319775(EPHX1) 109319862
GGN109296897(EPHX1)
PSS102456152 102457257(EPHX1)
CMY102934448(EPHX1) 102942209
CPIC101936865(EPHX1) 101949762
TST117874510(EPHX1) 117874592
CABI116819064 116823869(EPHX1)
MRV120400560(EPHX1) 120400786
ACS100554472 100555586(ephx1)
PVT110075401(EPHX1)
SUND121915364(EPHX1) 121934079
PBI103058096(EPHX1)
PMUR107289275(EPHX1)
CTIG120307226(EPHX1) 120307716
TSR106541570 106542798(EPHX1)
PGUT117671761(EPHX1) 117671857
VKO123025614(EPHX1) 123032030
PMUA114594523 114594618(EPHX1)
ZVI118081778 118083220(EPHX1)
GJA107119060(EPHX1)
STOW125425855 125437417(EPHX1)
XLA108716563 432100(ephx1.L)
XTR100158543(ephx1) 105946059
NPR108787057(EPHX1) 108802126
RTEM120937855(EPHX1) 120938076 120938077
BBUF120999601(EPHX1) 120999807 120999808 120999809
BGAR122931001 122931002 122931003 122934641(EPHX1)
DRE394043(ephx1)
SRX107732537
SANH107690044(ephx1)
SGH107553477 107601524
CCAR109080243
CAUA113056744 113062837 113063108 113120712
PPRM120493268(ephx1)
MAMB125278271(ephx1)
IPU108263372(ephx5)
PHYP113542048(ephx1)
SMEO124376972(ephx1)
TFD113647581(ephx1)
AMEX103040834(ephx1)
EEE113587098(ephx1)
TRU101066103(ephx1)
TNGGSTEN00030811G001
LCO104918259 104918311(ephx1)
NCC104963447(ephx1)
CGOB115003531(ephx1) 115020096
ELY117248410(ephx5) 117271285(ephx1)
EFO125897156(ephx1) 125903794(ephx5)
PLEP121954425(ephx5) 121955668(ephx1) 121964048
SLUC116051469(ephx5) 116065557(ephx1)
ECRA117960017(ephx5) 117961646(ephx1)
ESP116705706 116705884(ephx1)
PFLV114571843 114573297(ephx1)
GAT120807746(ephx1) 120820603(ephx5)
PPUG119194870(ephx1) 119214299(ephx5)
MSAM119909018(ephx1) 119916924(ephx5) 119918272
CUD121506648(ephx1) 121510636 121510637 121510638
ALAT119012274(ephx1) 119033157 119033158
MZE101463752 101487605(ephx1)
ONL100693015(ephx1) 100711364 100711636
OAU116314224(ephx1) 116318528
OLA101166982 101172051(ephx1)
OML112141000(ephx1) 112161741(ephx5)
XMA102229129 102230310(ephx1)
XCO114138263 114158698(ephx1)
XHE116713645 116734282(ephx1)
PRET103477226
PFOR103134161(ephx1)
PLAI106961696(ephx1)
PMEI106930043(ephx1)
GAF122824815(ephx1) 122842946(ephx5)
CVG107093270(ephx1)
CTUL119797626(ephx5) 119797636(ephx1)
GMU124859323(ephx5) 124881512(ephx1)
NFU107375461
KMR108233942(ephx5) 108246518(ephx1)
ALIM106515907 106532950(ephx1)
NWH119417756(ephx5) 119417998(ephx1)
AOCE111583489(ephx1) 111585235
MCEP124999376(ephx1) 125019156(ephx5)
CSEM103380678(ephx1)
POV109632306(ephx1)
SSEN122784166(ephx1)
HHIP117758195(ephx1)
HSP118099717(ephx1)
LCF108877099(ephx5) 108901766
SDU111220582 111239530(ephx1)
SLAL111661516(ephx1)
XGL120788741(ephx1) 120796290(ephx5)
HCQ109516170 109524815
BPEC110154206(ephx1)
MALB109958771(ephx1)
BSPL114870553(ephx5)
SASA106571450 106607860
STRU115174737 115192170 115201724
OTW112250359(ephx1) 112261919
OMY110499486(ephx5) 110499548 110522278 110529658
OGO123990800 123995128 124040433(ephx5)
ONE115107806 115118720 115139362 115144473
SALP111954385 111973113
SNH120019006 120024146 120029362 120029363 120029925 120029926
CCLU121547755(ephx5) 121548868 121552613
ELS105017773(ephx1)
SFM108925178(ephx1)
PKI111854029(ephx1)
AANG118217958(ephx5) 118230719(ephx1)
LOC102682886(ephx1) 102687913
PSPA121315717 121315718
ARUT117402351(ephx5) 117402598
LCM102353239(EPHX1)
CMK103181611
RTP109925374(ephx1)
BFO118403733 118403746 118404497 118404498 118404531 118418327
BBEL109476326 109476397
CIN100176449
SCLV120335264
SPU588166
APLC110978249
SKO100371948
RZE108357011
VPS122631147
HHAL106691877
DPXDAPPUDRAFT_301203
DMK116921463
PVM113814676
PJA122245739 122245740
PCHN125032423 125032480 125032492
HAME121867766
PCLA123770507
PTRU123501561
HAZT108672100
EAF111705076 111705077
DSV119461825
VDE111248235
VJA111259854
TUT107364002
DPTE113797953 113798526
DFR124490217 124493950
CSCU111622807
PTEP107446491
SDM118180616
CELCELE_W01A11.1(W01A11.1)
CBRCBG_18950
LOALOAG_01695
NAINECAME_00373
TSPTsp_04403
LAK106154062
NVE5500949
EPA110242247
ADF107344265
AMIL114972824 114974329
PDAM113677512
SPIS111325313
XEN124459167
TADTRIADDRAFT_63297
QSU112010208
NCRNCU08783
NTENEUTE1DRAFT122640(NEUTE1DRAFT_122640)
SMPSMAC_04550
PANPODANSg1577
MTMMYCTH_2120346
MGRMGG_14882
PPEIPpBr36_06535
SSCKSPSK_07616
FGRFGSG_01765
FPUFPSE_11393
FVRFVEG_12319
FOXFOXG_13212
NHENECHADRAFT_53192
TRETRIREDRAFT_64469
TRRM419DRAFT_36708
MAWMAC_05449
MAJMAA_09463
CMTCCM_05222
CFJCFIO01_01286
CLUPCLUP02_04735 CLUP02_07353
CHIGCH63R_03746 CH63R_06191 CH63R_09604
ELAUCREL1_8323
PFYPFICI_13875
BFUBCIN_14g05560
MBEMBM_02500
PSCOLY89DRAFT_710694
GLZGLAREA_08702 GLAREA_12516
ANIAN3017.2
AFMAFUA_2G14860 AFUA_3G08960
ACTACLA_036930
NFINFIA_068170
AORAO090005001384
ANGANI_1_1072104(An12g08930) ANI_1_312144(An16g02170)
AFVAFLA_004204
ALUCAKAW2_61223A AKAW2_70182A
ACHEACHE_40396A
APUUAPUU_30512A APUU_60886A
PCSPc20g03890
PDPPDIP_08560
TMFPMAA_029110
TRGTRUGW13939_03191 TRUGW13939_06026
PBNPADG_00494
BGHBDBG_05030
PNOSNOG_02284
PTEPTT_15786
BZECOCCADRAFT_33094
BSCCOCSADRAFT_185751
BORCOCMIDRAFT_107314
AALTCC77DRAFT_1022077 CC77DRAFT_801013
ZTRMYCGRDRAFT_71676
PFJMYCFIDRAFT_52339
FFUCLAFUR5_02648 CLAFUR5_03954 CLAFUR5_04468 CLAFUR5_14183
BCOMBAUCODRAFT_490072
NPAUCRNP2_8786
CNECNN02220
CNBCNBN2260
CNGCNAG_06497
CGICGB_N3310C
TMSTREMEDRAFT_45464
TASAA1Q1_01368
BURBcep18194_B1704
PUBSAR11_0803(ephX1)
BCLABC1387
FRAFrancci3_2199
FALFRAAL2594 FRAAL3740
 » show all
Reference
1  [PMID:4998715]
  Authors
Oesch F, Daly J.
  Title
Solubilization, purification, and properties of a hepatic epoxide hydrase.
  Journal
Biochim Biophys Acta 227:692-7 (1971)
DOI:10.1016/0005-2744(71)90018-0
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 3:305-40 (1973)
DOI:10.3109/00498257309151525
Reference
4  [PMID:4463951]
  Authors
Oesch F.
  Title
Purification and specificity of a human microsomal epoxide hydratase.
  Journal
Biochem J 139:77-88 (1974)
DOI:10.1042/bj1390077
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 250:8283-8 (1975)
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 6:577-82 (1994)
DOI:10.1002/chir.530060711
Reference
7  [PMID:11154734]
  Authors
Fretland AJ, Omiecinski CJ.
  Title
Epoxide hydrolases: biochemistry and molecular biology.
  Journal
Chem Biol Interact 129:41-59 (2000)
DOI:10.1016/S0009-2797(00)00197-6
Reference
8  [PMID:15822179]
  Authors
Morisseau C, Hammock BD.
  Title
Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles.
  Journal
Annu Rev Pharmacol Toxicol 45:311-33 (2005)
DOI:10.1146/annurev.pharmtox.45.120403.095920
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 44:1-51 (2005)
DOI:10.1016/j.plipres.2004.10.001
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 45:966-973 (2017)
DOI:10.1124/dmd.117.076489
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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