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Information on EC 3.3.2.9 - microsomal epoxide hydrolase
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3.3.2.9 microsomal epoxide hydrolaseIUBMB Comments
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).
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Word Map
- 3.3.2.9
- phenobarbital
- cholesterol
- phospholipid
- hepatocytes
- monooxygenase
- hydroxylase
- triglyceride
- xenobiotics
- steroid
-
nadph-cytochrome
- thyroid
- isozymes
- lipoprotein
- s-transferase
- testosterone
- aniline
-
benzoapyrene
- phosphatidylcholine
-
glucuronidation
- 3-methylcholanthrene
- bile
-
drug-metabolizing
-
arachidonic
- prostaglandin
- acyltransferase
- heme
-
hepatotoxicity
-
nadph-dependent
- cyp2e1
- gsh
- autoimmune
-
apolipoprotein
- cyp1a2
- autoantibody
- biphenyls
-
polycyclic
-
udp-glucuronosyltransferase
- monoxide
- glucose-6-phosphatase
-
tetrachloride
-
polychlorinated
- thyroglobulin
- ketoconazole
- demethylase
- ccl4
-
desaturation
- n-oxide
- androstenedione
-
beta-hydroxysteroid
- 21-hydroxylase
- synthesis
- medicine
- drug development
- analysis
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
Synonyms
microsomal, meh, microsomal epoxide hydrolase, ephx1, mephx, microsomal eh, jh epoxide hydrolase, juvenile hormone epoxide hydrolase, microsomal epoxide hydrolase 1, xenobiotic epoxide hydrolase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
EC 3.3.2.3
-
-
formerly, part transferred
-
EC 4.2.1.63
-
-
formerly, part transferred
-
EC 4.2.1.64
-
-
formerly, part transferred
-
EHb
EPHX1
epoxide hydrolase
mEH
Microsomal epoxide hydrolase
SEH
xenobiotic epoxide hydrolase
additional information
EPHX1
-
-
EPHX1
-
EPHX1 detoxifies genotoxic compounds and participates in the removal of reactive oxygen species
mEH
-
-
mEH
-
mEH is mainly involved in the detoxification of wide variety of endogenous or exogenous carcinogens
mEH
-
-
mEH
-
-
additional information
-
microsomal epoxide hydrolase is a member of the family of epoxide hydrolases
additional information
-
the enzyme belongs to the family of C-X bond hydrolase enzymes
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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
(2)
-
-
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
active site structure, quantitative structure-activity relationships, molecular modelling
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
formation of threo-1,2-diphenyl-1,2-ethanediols from all epoxides involving anti-stereospecific opening of the oxirane ring with about 90% preference for the (S)-carbon to give nearly optically pure (R,R)-diols
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
reaction mechanism, catalytic triad
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
reaction mechanism, catalytic triad
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
reaction mechanism, catalytic triad
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
reaction mechanism, catalytic triad
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
reaction mechanism, catalytic triad
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
reaction mechanism, catalytic triad
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
reaction mechanism, catalytic triad
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
reaction mechanism, catalytic triad
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
reaction mechanism, catalytic triad
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
the catalytic triad is Asp223-Glu402-His429, the active site includes an oxyanion hole
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
the catalytic triad is Asp226-His431-Asp352, catalytic mechanism involving an ester intermediate formed by alkylation of an active site carboxyl group
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
two step mechanism with formation of of a hydroxyl-alkyl-enzyme intermediate, catalytic triad
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
two step mechanism with formation of of a hydroxyl-alkyl-enzyme intermediate, catalytic triad
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
two step mechanism with formation of of a hydroxyl-alkyl-enzyme intermediate, the catalytic triad is Asp226-His431-Glu404 with polarizing residues Tyr299 and Tyr374
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
(1)
-
-
-
cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
ring-opening reaction mechanism, overview
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cyclization
-
In the case of non-ladder polyethers, the majority of epoxide ring opening reactions proceed via attack at the proximal carbon (exo-tet cyclization) while polyether ladder formation requires attack at the distal carbon (endo-tet cyclization)
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
cis-stilbene-oxide hydrolase
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).
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CAS REGISTRY NUMBER
COMMENTARY
9048-63-9
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(3-(4-(2-oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-ethoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone + H2O
(3-[4-[([[3-(hydroxymethyl)oxetan-3-yl]methyl]amino)methyl]phenoxy]azetidin-1-yl)[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]methanone
-
-
-
-
?
(3-(4-(2-oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-ethoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone + H2O
?
-
-
-
-
?
(3-(4-(2-oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-ethoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone + H2O
[3-(4-[[3,3-bis(hydroxymethyl)azetidin-1-yl]methyl]phenoxy)azetidin-1-yl][5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]methanone
-
-
-
-
?
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O
(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid
(5Z,8Z,11Z)-14,15-epoxyeicosa-5,8,11-trienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosa-5,8,11-trienoic acid
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
(5Z,8Z,14Z)-11,12-epoxyeicosa-5,8,14-trienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosa-5,8,14-trienoic acid
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O
(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid
(R)-1,2-epoxybutane + H2O
(2R)-butane-1,2-diol
very limited preference for hydrolysis of the (R)-enantiomer
-
-
?
(R)-epichlorhydrin + H2O
(R)-3-chloro-1,2-propanediol
very limited preference for hydrolysis of the (S)-enantiomer
-
-
?
(R)-glycidyl tosylate + H2O
(2R)-4-(4-methylbenzene-1-sulfonyl)butane-1,2,4-triol
very limited preference for hydrolysis of the (R)-enantiomer
-
-
?
(R)-styrene oxide + H2O
(R)-styrene glycol
preferential hydrolysis of the (R)-enantiomer
-
-
?
(S)-1,2-epoxybutane + H2O
(2S)-butane-1,2-diol
very limited preference for hydrolysis of the (R)-enantiomer
-
-
?
(S)-epichlorhydrin + H2O
(S)-3-chloro-1,2-propanediol
very limited preference for hydrolysis of the (S)-enantiomer
-
-
?
(S)-glycidyl tosylate + H2O
(2S)-4-(4-methylbenzene-1-sulfonyl)butane-1,2,4-triol
very limited preference for hydrolysis of the (R)-enantiomer
-
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
1,2,3,4,9,9-hexachloro-1,4,4a,5,6,7,8,8a-octahydro-1,4-methanonaphthalene-6,7-diol
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
-
-
-
ir
1-[3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]ethan-1-one + H2O
1-[3-[4-([[3-hydroxy-2-(hydroxymethyl)-2-methylpropyl](methyl)amino]methyl)phenoxy]azetidin-1-yl]ethan-1-one
-
[3-hydroxy-2-(hydroxymethyl)-2-methylpropyl](methyl)amino]methyl)phenoxy]azetidin-1-yl]ethan-1-one
-
ir
2,3-epoxypropyl-p-methoxyphenyl ether + H2O
3-(3-methoxyphenoxy)propane-1,2-diol
-
-
-
-
?
2-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]ethan-1-amine + H2O
2-([[2-(4-methoxyphenyl)ethyl](methyl)amino]methyl)-2-methylpropane-1,3-diol
-
-
-
ir
2-methyl styrene oxide + H2O
(2R)-2-phenylpropane-1,2-diol
-
-
highly enantioselective in ionic liquid [bmim][PF6]in presence of 10% water
-
?
4-nitrostyrene 7,8-oxide + H2O
1-(4-nitro)phenyl-ethane-1,2-diol
-
i.e. PNSO
-
-
?
4-t-butylstyrene oxide + H2O
(1R)-1-(4-t-butylphenyl)ethane-1,2-diol
-
-
highly enantioselective in ionic liquid [bmim][PF6]in presence of 10% water
-
?
7,12-dimethylbenz[a]anthracene + 3 H2O
7,12-dimethylbenz[a]anthra-3,4-diol-1,2-epoxide
-
-
-
?
7,12-dimethylbenz[a]anthracene + 3 H2O
7,12-dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide
7-glycidoxycoumarin + H2O
7-(1',2'-dihydroxy-3'-propoxy)coumarin
-
substrate is a stable epoxide
-
-
?
cis-(9R,10S)-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
cis-(9R,10S)-epoxystearic acid methyl ester + H2O
threo-(9R,10R)-dihydroxystearic acid methyl ester + threo-(9S,10S)-dihydroxystearic acid methyl ester
cis-(9S,10R)-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
cis-(9S,10R)-epoxystearic acid methyl ester + H2O
threo-(9R,10R)-dihydroxystearic acid methyl ester + threo-(9S,10S)-dihydroxystearic acid methyl ester
cis-4,4'-dichlorostilbene oxide + H2O
(1R,2R)-1,2-bis(4-chlorophenyl)ethane-1,2-diol
-
-
product identification
-
?
cis-4,4'-diethylstilbene oxide + H2O
(1R,2R)-1,2-bis(4-ethylphenyl)ethane-1,2-diol
-
-
product identification
-
?
cis-4,4'-diisopropylstilbene oxide + H2O
(1R,2R)-1,2-bis(4-isopropylphenyl)ethane-1,2-diol
-
-
product identification
-
?
cis-4,4'-dimethylstilbene oxide + H2O
(1R,2R)-1,2-bis(4-methylphenyl)ethane-1,2-diol
-
-
product identification
-
?
cyano(2-methoxynaphthalen-6-yl)methyl trans-(2-(3-phenyloxiran-2-yl))acetate + H2O
?
-
-
-
?
cyano(6-methoxy-naphthalen-2-yl)methyl oxiran-2-ylmethyl carbonate + H2O
?
-
-
-
?
cyano(6-methoxy-naphthalen-2-yl)methyl trans-[(3-phenyloxiran-2-yl)methyl]carbonate + H2O
?
-
-
-
?
cyano-(6-methoxy-naphthalen-2-yl)-methyl 3,3-dimethyl-oxiranylmethyl carbonate + H2O
?
-
-
-
?
cyano-(6-methoxy-naphthalen-2-yl)-methyl trans-((3-ethyl-oxiran-2-yl)methyl) carbonate + H2O
?
-
-
-
?
cyano-(6-methoxynaphthalen-2-yl)methyl trans-2-pentenylacetate + H2O
?
-
prepared from trans-styrylacetic acid and 7-methoxy-2-naphthaldehyde. Enzyme EH catalyzed hydrolysis of the epoxide substrate produces an intermediate diol which lactonizes to release a fluorescent reporter after hydrolysis of the intermediate cyanohydrin
-
-
?
dihydronaphthalene oxide + H2O
(1S,2S)-1,2,3,4-tetrahydronaphthalene-1,2-diol
-
-
highly enantioselective in ionic liquid [bmim][PF6]in presence of 10% water
-
?
epoxy-stearic acid + H2O
?
-
highly enantiospecific reaction, low activity
-
-
?
racemic cis-9,10-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
trans-4,5-epoxy-hexanol
1-(tetrahydrofuran-2-yl)ethanol
-
exo-tet cyclization reaction
-
-
?
trans-4,5-epoxy-hexanol
2-methyltetrahydro-2H-pyran-3-ol
-
endo-tet cyclization reaction
-
-
?
[3-(4-[[(oxetan-3-yl)amino]methyl]phenoxy)azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone + H2O
[3-(4-[[(1,3-dihydroxypropan-2-yl)amino]methyl]phenoxy)azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone
-
-
-
ir
[3-[4-([((3-methyloxetan-3-yl)methyl)amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone + H2O
[3-[4-([[3-hydroxy-2-(hydroxymethyl)-2-methylpropyl]amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone
-
-
-
ir
[3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone + H2O
[3-[4-([[3-hydroxy-2-(hydroxymethyl)-2-methylpropyl](methyl)amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone
-
-
-
ir
[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-(4-[[(oxetan-3-yl)amino]methyl]phenoxy)azetidin-1-yl]methanone + H2O
[3-(4-[[(1,3-dihydroxypropan-2-yl)amino]methyl]phenoxy)azetidin-1-yl][5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]methanone
-
-
-
ir
[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone + H2O
[3-[4-([[3-hydroxy-2-(hydroxymethyl)-2-methylpropyl](methyl)amino]methyl)phenoxy]azetidin-1-yl][5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]methanone
-
-
-
ir
[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone + H2O
[3-[4-([[3-hydroxy-2-(hydroxymethyl)-2-methylpropyl]amino]methyl)phenoxy]azetidin-1-yl][5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]methanone
-
-
-
ir
[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([[(oxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone + H2O
[3-[4-([[3-hydroxy-2-(hydroxymethyl)propyl]amino]methyl)phenoxy]azetidin-1-yl][5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]methanone
-
-
-
ir
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O
(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O
(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,14Z)-11,12-epoxyeicosa-5,8,14-trienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosa-5,8,14-trienoic acid
-
i.e. 11,12-EET
i.e. 11,12-DHET
-
?
(5Z,8Z,14Z)-11,12-epoxyeicosa-5,8,14-trienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosa-5,8,14-trienoic acid
-
i.e. 11,12-EET
i.e. 11,12-DHET
-
?
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid
-
-
-
-
?
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O
(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid
-
-
-
-
?
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O
(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid
-
-
-
-
?
(R)-styrene oxide + H2O
(1R)-1-phenylethane-1,2-diol
-
R-enantiomer is preferred
-
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
?
-
-
-
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
?
-
-
-
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
?
-
-
-
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
?
-
-
-
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
?
Pigeon
-
-
-
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
?
quail
-
-
-
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
?
-
-
-
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
?
-
-
-
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
?
toad
-
-
-
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
?
trout
-
-
-
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
1,2,3,4,9,9-hexachloro-1,4,4a,5,6,7,8,8a-octahydro-1,4-methanonaphthalene-6,7-diol
-
excellent and selective substrate for mEH
-
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
1,2,3,4,9,9-hexachloro-1,4,4a,5,6,7,8,8a-octahydro-1,4-methanonaphthalene-6,7-diol
-
excellent and selective substrate for mEH
-
-
?
16,17-epoxyandrost-4-en-3-one + H2O
16,17-dihydroxyandrost-4-en-3-one
-
high activity
-
-
?
16,17-epoxyandrost-4-en-3-one + H2O
16,17-dihydroxyandrost-4-en-3-one
-
high activity
-
-
?
16,17-epoxyandrost-4-en-3-one + H2O
16,17-dihydroxyandrost-4-en-3-one
-
high activity
-
-
?
16alpha,17alpha-epoxyandrosten-3-one + H2O
?
-
endogenous substrate of mEH
-
-
?
16alpha,17alpha-epoxyandrosten-3-one + H2O
?
-
endogenous substrate of mEH
-
-
?
4-methyl-2-oxo-2H-chromen-7-yl oxiran-2-ylmethyl carbonate + H2O
?
-
-
-
-
?
4-vinylcyclohexene + H2O
?
-
-
after exposure of ovary to 4-vinylcyclohexene, an inactive tetrol metabolite 4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane can be formed, potentially through detoxification action of mEH
-
?
4-vinylcyclohexene diepoxide + H2O
4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane
-
-
-
-
?
4-vinylcyclohexene diepoxide + H2O
4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane
-
-
-
?
4-vinylcyclohexene diepoxide + H2O
4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane
-
-
-
-
?
4-vinylcyclohexene diepoxide + H2O
4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane
-
-
-
?
4-vinylcyclohexene diepoxide + H2O
4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane
-
-
-
?
7,12-dimethylbenz[a]anthracene + 3 H2O
7,12-dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide
-
-
-
?
7,12-dimethylbenz[a]anthracene + 3 H2O
7,12-dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide
-
-
bioactivation reaction
-
?
7,12-dimethylbenz[a]anthracene + 3 H2O
7,12-dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide
-
-
-
?
benzopyrene 4,5-oxide + H2O
(-)benzopyrene 4,5-dihydrodiol
-
-
-
-
?
benzopyrene 4,5-oxide + H2O
(-)benzopyrene 4,5-dihydrodiol
-
-
-
-
?
benzopyrene 4,5-oxide + H2O
(-)benzopyrene 4,5-dihydrodiol
-
-
-
-
?
benzopyrene 4,5-oxide + H2O
(-)benzopyrene 4,5-dihydrodiol
-
-
-
-
?
benzopyrene 7,8-oxide + H2O
?
-
-
-
-
?
cis-(9R,10S)-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
-
-
enantioselective production of 80% (9R,10R)-diol and 20% (9S,10S)-diol
-
?
cis-(9R,10S)-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
-
-
enantioselective production of 84% (9R,10R)-diol and 16% (9S,10S)-diol
-
?
cis-(9R,10S)-epoxystearic acid methyl ester + H2O
threo-(9R,10R)-dihydroxystearic acid methyl ester + threo-(9S,10S)-dihydroxystearic acid methyl ester
-
-
enantioselective production of 79% (9R,10R)-diol and 21% (9S,10S)-diol
-
?
cis-(9R,10S)-epoxystearic acid methyl ester + H2O
threo-(9R,10R)-dihydroxystearic acid methyl ester + threo-(9S,10S)-dihydroxystearic acid methyl ester
-
-
enantioselective production of 83% (9R,10R)-diol and 17% (9S,10S)-diol
-
?
cis-(9S,10R)-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
-
-
enantioselective production of 39% (9R,10R)-diol and 61% (9S,10S)-diol
-
?
cis-(9S,10R)-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
-
-
enantioselective production of 52% (9R,10R)-diol and 48% (9S,10S)-diol
-
?
cis-(9S,10R)-epoxystearic acid methyl ester + H2O
threo-(9R,10R)-dihydroxystearic acid methyl ester + threo-(9S,10S)-dihydroxystearic acid methyl ester
-
-
enantioselective production of 48% (9R,10R)-diol and 52% (9S,10S)-diol
-
?
cis-(9S,10R)-epoxystearic acid methyl ester + H2O
threo-(9R,10R)-dihydroxystearic acid methyl ester + threo-(9S,10S)-dihydroxystearic acid methyl ester
-
-
enantioselective production of 68% (9R,10R)-diol and 32% (9S,10S)-diol
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
the recombinant enzyme expressed in Escherichia coli acts stereospecifically on the the (R)-styrene
-
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
?
cis-stilbene oxide + H2O
(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
-
?
cis-stilbene oxide + H2O
(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
-
?
cis-stilbene oxide + H2O
(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
-
?
cis-stilbene oxide + H2O
(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
-
?
cyano(2-methoxynaphthalen-6-yl)methyl trans-2-(3-propyloxiran-2-yl)acetate + H2O
?
-
-
-
?
cyano(2-methoxynaphthalen-6-yl)methyl trans-2-(3-propyloxiran-2-yl)acetate + H2O
?
-
-
-
-
?
cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate + H2O
?
-
synthetic fluorescent substrate
-
-
?
cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate + H2O
?
-
synthetic fluorescent substrate
-
-
?
cytochrome P450 isoform 1B1 + H2O
7,12-dimethylbenz(a)anthracene-3,4-diol
-
-
-
-
?
cytochrome P450 isoform 1B1 + H2O
7,12-dimethylbenz(a)anthracene-3,4-diol
-
-
-
-
?
juvenile hormone III + H2O
?
-
activity is less than 4 pmol/min/mg protein
-
?
phenanthrene-9,10-oxide + H2O
?
-
-
-
-
?
racemic cis-9,10-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
-
30% enantioselective (9S,10S)-cis-diol production
-
-
?
racemic cis-9,10-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
-
94% enantioselective (9S,10S)-cis-diol production
-
-
?
racemic cis-9,10-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
-
63.5% enantioselective (9S,10S)-cis-diol production
-
-
?
racemic cis-9,10-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
-
94% enantioselective (9S,10S)-cis-diol production
-
-
?
racemic cis-9,10-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
-
74% enantioselective (9S,10S)-cis-diol production
-
-
?
racemic cis-9,10-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
-
90% enantioselective (9S,10S)-cis-diol production by the constitutive enzyme, 86% by the pathogen-induced enzyme
-
-
?
racemic cis-9,10-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
-
59% enantioselective (9S,10S)-cis-diol production
-
-
?
racemic ethyl 3-phenylglycidate + H2O
(2R,3S)-ethyl 3-phenylglycidate
-
-
production of (2R,3S)-ethyl 3-phenylglycidate with 95% enantiomeric excess and 26% yield in 12 h from 0.2% (w/v) of the racemat
-
?
racemic ethyl 3-phenylglycidate + H2O
(2R,3S)-ethyl 3-phenylglycidate
-
-
production of (2R,3S)-ethyl 3-phenylglycidate with 95% enantiomeric excess and 26% yield in 12 h from 0.2% (w/v) of the racemat
-
?
styrene 7,8-oxide + H2O
styrene glycol
-
-
-
-
?
styrene oxide + H2O
1-phenylethane-1,2-diol
-
recombinant enzyme, low activity
-
-
?
trans-9,10-epoxystearate + H2O
9,10-dihydroxy-octadecanoic acid
-
-
-
-
?
trans-stilbene oxide + H2O
1,2-diphenylethane-1,2-diol
-
-
-
?
trans-stilbene oxide + H2O
?
-
cis-stilbene oxide hydrolase and trans-stilbene hydrolase isoenzymes are not structurally identical
-
-
?
additional information
?
-
-
enantioselectivity with fatty acid epoxide substrates
-
-
?
additional information
?
-
-
enzyme is induced by a number of xenobiotics, the enzyme is thought to play a detoxifying role by preventing epoxides from reacting irreversibly with critical cellular macromolecules. Some evidence exists to support the hypothesis that microsomal epoxide hydrolase is closely associated with at least certain forms of cytochrome P-450, such association may influence the functional role of the microsomal epoxide hydrolase in the various pathways of bioactivation
-
-
?
additional information
?
-
the enzyme in Drosophila melanogaster is involved in xenobiotic biotransformation, but not in juvenile hormone metabolism
-
-
?
additional information
?
-
-
the enzyme in Drosophila melanogaster is involved in xenobiotic biotransformation, but not in juvenile hormone metabolism
-
-
?
additional information
?
-
-
enantioselectivity with fatty acid epoxide substrates
-
-
?
additional information
?
-
no activity with trans-stilbene oxide
-
-
?
additional information
?
-
-
no activity with trans-stilbene oxide
-
-
?
additional information
?
-
-
enzyme is induced by a number of xenobiotics, the enzyme is thought to play a detoxifying role by preventing epoxides from reacting irreversibly with critical cellular macromolecules. Some evidence exists to support the hypothesis that microsomal epoxide hydrolase is closely associated with at least certain forms of cytochrome P-450, such association may influence the functional role of the microsomal epoxide hydrolase in the various pathways of bioactivation
-
-
?
additional information
?
-
-
involved in the biotransformation of epoxides produced from either xeno- or endobiotics. The diols produced are generally detoxification products but in several instances, such as 9,10-epoxybenzopyrene-7,8-diol, they are very potent mutagens and possible carcinogens. The enzyme is induced by phenobarbital
-
-
?
additional information
?
-
-
the enzyme is expected to play a purely protective role with respect to epoxides metabolically produced from pharmaceutical drugs
-
-
?
additional information
?
-
-
genetic polymorphisms of the enzyme are responsible for varying susceptibility of cigarette smoking humans to chronic obstructive pulmonary disease, COPD
-
-
?
additional information
?
-
-
key enzyme in the metabolism of environmental contaminants being responsible for xenobiotic transformations, regulation of the enzyme occurs at transcriptional, translational, and post-translational level, the enzyme is also involved in cytoprotection and steroid metabolism, as well as in cellular responses to glucose metabolism and in Na+-dependent bile acid transport, the enzyme is part of a multi-transport system at the cell surface
-
-
?
additional information
?
-
-
the enzyme is a phase II biotransformation enzyme which detoxifies epoxides, including carcinogens such as polycyclic aromatic hydrocarbons found in cigarette smoke and cooked meats, enzyme polymorphisms are not associated with colon cancer risk
-
-
?
additional information
?
-
-
the enzyme is critical for biotransformations in xenobiotic metabolism and detoxification
-
-
?
additional information
?
-
-
the enzyme is involved in xenobiotic metabolism and detoxification, e.g. of 1,3-butadiene oxide, styrene oxide, and benzo[a]pyrene-4,5-oxide, enzyme deficiency leads to acute and severe phenytoin toxicity in vivo, the enzyme is involved in transport of bile acids in the liver
-
-
?
additional information
?
-
-
mEH prefers mono- and cis-substituted epoxides, low but highly enantioselective activity with epoxy fatty acids
-
-
?
additional information
?
-
-
substrate specificity, no activity with 1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene,i.e. HEOM, 2-acetylaminofluorene, arochlor 1254, and benzopyrene 4,5-oxide, the cytosolic enzyme hydrates epoxides on cyclic sytems very slowly, but hydrates a wide variety of aliphatic epoxides rapidly, trisubstituted terpenoid epoxides show low Km-values, fatty acid and ester epoxides are hydrated very quickly
-
-
?
additional information
?
-
-
wide substrate specificity, epoxide-containing glycerol-phospholipids are poor substrates, the enzyme prefers mono- and cis-1,2-disubstituted epoxides as substrates, while gem-di-, trans-di-, tri- and tetra-substituted epoxides are either low turnover substrates or inhibitors, the enzyme has a tamaoxifen binding site
-
-
?
additional information
?
-
-
EPHX1 detoxifies genotoxic compounds and participates in the removal of reactive oxygen species
-
-
?
additional information
?
-
-
mEH is capable of inactivating a large number of structurally different, highly reactive epoxides and hence is an important part of the enzymatic defence of our organism against adverse effects of foreign compounds
-
-
?
additional information
?
-
-
mEH mediates the transport of bile acid in the liver
-
-
?
additional information
?
-
-
mEH prefers mono- and cis-1,2-disubstituted epoxides, while gem-di-, trans-di-, tri- and tetrasubstituted epoxides are low-turnover substrates or inhibitors
-
-
?
additional information
?
-
-
no activity with 14,15-epoxyexicosatrienoic acid
-
-
?
additional information
?
-
enzyme mEH in collaboration with cytochrome-P-450 (CYP) converts benzo(a)pyrene to more reactive intermediate, benzo(a)pyrene-7,8-dihydrodiol 8,9-epoxide (benzo(a)pyrene diolepoxide, BPDE) which displays higher mutagenic and carcinogenic potential than its substrate
-
-
?
additional information
?
-
-
enzyme mEH in collaboration with cytochrome-P-450 (CYP) converts benzo(a)pyrene to more reactive intermediate, benzo(a)pyrene-7,8-dihydrodiol 8,9-epoxide (benzo(a)pyrene diolepoxide, BPDE) which displays higher mutagenic and carcinogenic potential than its substrate
-
-
?
additional information
?
-
oxetanes are a nonepoxide class of substrates for human mEH, which is known to catalyze the hydrolytic ring opening of electrophilic and potentially toxic epoxide-containing drugs, drug metabolites, and exogenous organochemicals
-
-
?
additional information
?
-
-
oxetanes are a nonepoxide class of substrates for human mEH, which is known to catalyze the hydrolytic ring opening of electrophilic and potentially toxic epoxide-containing drugs, drug metabolites, and exogenous organochemicals
-
-
?
additional information
?
-
the enzyme converts epoxides to diols and is able to either detoxify or bioactivate a wide range of substrates. The prototypical EPHX1 reaction involves conversion of epoxides to trans-dihydrodiols. EPHX1 more readily converts xenobiotics than endogenous substrates
-
-
?
additional information
?
-
-
the enzyme converts epoxides to diols and is able to either detoxify or bioactivate a wide range of substrates. The prototypical EPHX1 reaction involves conversion of epoxides to trans-dihydrodiols. EPHX1 more readily converts xenobiotics than endogenous substrates
-
-
?
additional information
?
-
EPHX1 has a broad substrate specificity. It also metabolizes endocannabinoid 2-arachidonoylglycerol to free arachidonic acid and glycerol
-
-
?
additional information
?
-
-
EPHX1 has a broad substrate specificity. It also metabolizes endocannabinoid 2-arachidonoylglycerol to free arachidonic acid and glycerol
-
-
?
additional information
?
-
no activity with [5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-(4-[[methyl(oxetan-3-yl)amino]methyl]phenoxy)azetidin-1-yl]methanone, [5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-(4-[[(3-methyloxetan-3-yl)amino]methyl]phenoxy)azetidin-1-yl]methanone, 2-(4-methoxyphenyl)-N-[(3-methyloxetan-3-yl)methyl]ethan-1-amine, and 2-(4-methoxyphenyl)-N-methyl-N-[(oxetan-3-yl)methyl]ethan-1-amine
-
-
?
additional information
?
-
-
no activity with [5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-(4-[[methyl(oxetan-3-yl)amino]methyl]phenoxy)azetidin-1-yl]methanone, [5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-(4-[[(3-methyloxetan-3-yl)amino]methyl]phenoxy)azetidin-1-yl]methanone, 2-(4-methoxyphenyl)-N-[(3-methyloxetan-3-yl)methyl]ethan-1-amine, and 2-(4-methoxyphenyl)-N-methyl-N-[(oxetan-3-yl)methyl]ethan-1-amine
-
-
?
additional information
?
-
the microsomal epoxide hydrolase (EPHX1) is inactive with cis- or trans-allylic epoxides, such as 9R,10R-trans-epoxy-13R-hydroxy-octadeca-11E-enoic acid, 9R,10S-cis-epoxy-13R-hydroxyoctadeca-11E-enoic acid, 12,13-trans-epoxy-octadeca-9E-enoic acid, and 12,13-cis-epoxy-octadeca-9E-enoic acid, in contrast to the soluble epoxide hydrolase, (EPHX2 and EPHX3, EC 3.3.2.10)
-
-
?
additional information
?
-
-
the enzyme has the potential to catalyze the critical endo-tet cyclization of epoxy alcohols via a endo-tet cyclization, mechanism, overview. Reaction of polyepoxide pre-momensin to momensin, a polyether, or of another polyepoxide to brevetoxin B
-
-
?
additional information
?
-
-
substrate specificity, no activity with 1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene,i.e. HEOM, 2-acetylaminofluorene, arochlor 1254, and benzopyrene 4,5-oxide, the cytosolic enzyme hydrates epoxides on cyclic systems very slowly, but hydrates a wide variety of aliphatic epoxides rapidly, trisubstituted terpenoid epoxides show low Km-valus, fatty acid and ester epoxides are hydrated very quickly
-
-
?
additional information
?
-
-
the enzyme may play a significant role in the secondary metabolism of juvenile hormone acid generated by juvenile hormone esterase
-
-
?
additional information
?
-
-
enzyme is induced by a number of xenobiotics, the enzyme is thought to play a detoxifying role by preventing epoxides from reacting irreversibly with critical cellular macromolecules. Some evidence exists to support the hypothesis that microsomal epoxide hydrolase is closely associated with at least certain forms of cytochrome P-450, such association may influence the functional role of the microsomal epoxide hydrolase in the various pathways of bioactivation
-
-
?
additional information
?
-
-
the enzyme plays an important role in the metabolism of various xenobiotic compounds including the polycyclic aromatic hydrocarbon carcinogens. It is specifically involved in the formation of the ultimate carcinogen of benzopyrene
-
-
?
additional information
?
-
-
probably represents an important factor in the control of reactive epoxides
-
-
?
additional information
?
-
-
key enzyme in the metabolism of environmental contaminants being responsible for xenobiotic transformations, regulation of the enzyme occurs at transcriptional, translational, and post-translational level. The enzyme is also involved in cytoprotection and steroid metabolism, as well as in cellular responses to glucose metabolism and in Na+-dependent bile acid transport. The enzyme is part of a multi-transport system at the cell surface
-
-
?
additional information
?
-
-
the enzyme is involved in xenobiotic metabolism and detoxification, e.g. of 1,3-butadiene oxide, styrene oxide, and benzo[a]pyrene-4,5-oxide, the enzyme is important in sexual development
-
-
?
additional information
?
-
-
mEH prefers mono- and cis-substituted epoxides, low but highly enantioselective activity with epoxy fatty acids, the enzyme acts as an antiestrogen binding site subunit
-
-
?
additional information
?
-
-
substrate specificity, no activity with 1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene,i.e. HEOM, 2-acetylaminofluorene, arochlor 1254, and benzopyrene 4,5-oxide, the cytosolic enzyme hydrates epoxides on cyclic sytems very slowly, but hydrates a wide variety of aliphatic epoxides rapidly, trisubstituted terpenoid epoxides show low Km-values, fatty acid and ester epoxides are hydrated very quickly
-
-
?
additional information
?
-
-
wide substrate specificity, the enzyme prefers mono- and cis-1,2-disubstituted epoxides as substrates, while gem-di-, trans-di-, tri- and tetra-substituted epoxides are either low turnover substrates or inhibitors
-
-
?
additional information
?
-
-
mEH is capable of inactivating a large number of structurally different, highly reactive epoxides and hence is an important part of the enzymatic defence of our organism against adverse effects of foreign compounds
-
-
?
additional information
?
-
-
mEH mediates the transport of bile acid in the liver
-
-
?
additional information
?
-
-
mEH prefers mono- and cis-1,2-disubstituted epoxides, while gem-di-, trans-di-, tri- and tetrasubstituted epoxides are low-turnover substrates or inhibitors
-
-
?
additional information
?
-
microsomal epoxide hydrolase (mEH) has a wide substrate specificity
-
-
?
additional information
?
-
-
microsomal epoxide hydrolase (mEH) has a wide substrate specificity
-
-
?
additional information
?
-
-
enantioselectivity with fatty acid epoxide substrates
-
-
?
additional information
?
-
-
enantioselectivity with fatty acid epoxide substrates
-
-
?
additional information
?
-
-
substrate specificity, no activity with 1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene,i.e. HEOM, 2-acetylaminofluorene, arochlor 1254, and benzopyrene 4,5-oxide, the cytosolic enzyme hydrates epoxides on cyclic sytems very slowly, but hydrates a wide variety of aliphatic epoxides rapidly, trisubstituted terpenoid epoxides show low Km-values, fatty acid and ester epoxides are hydrated very quickly
-
-
?
additional information
?
-
-
the enzyme shows a broad substrate specificity, all epoxides with a trisubstituted oxirane ring are no or poor substrates, no activity with 5,6alpha-epoxy-5alpha-cholestan-3beta-ol
-
-
?
additional information
?
-
stereoselective hydrolysis of epoxyeicosatrienoic acids (EETs) by sEH
-
-
?
additional information
?
-
-
enantioselectivity with fatty acid epoxide substrates
-
-
?
additional information
?
-
the enzyme exhibits broad hydrolytic activity toward several racemic epoxides including styrene oxide, epichlorohydrin, and 1,2-epoxybutane
-
-
?
additional information
?
-
-
enzyme is induced by a number of xenobiotics, the enzyme is thought to play a detoxifying role by preventing epoxides from reacting irreversibly with critical cellular macromolecules. Some evidence exists to support the hypothesis that microsomal epoxide hydrolase is closely associated with at least certain forms of cytochrome P-450, such association may influence the functional role of the microsomal epoxide hydrolase in the various pathways of bioactivation
-
-
?
additional information
?
-
-
role in benzopyrene-induced mutagenesis and carcinogenesis
-
-
?
additional information
?
-
-
enzyme is involved in the metabolism of steroids, the microsomal enzyme plays a central role in both the inactivation of primary mutagenic and carcinogenic metabolites of polycyclic aromatic hydrocarbons, and in activating these metabolites to even more toxic or mutagenic secondary products, enzyme production is induced by 3-methylcholanthrene, phenobarbital, trans-stilbene oxide, 2(3)-tert-butyl-4-hydroxyanisol or 2-acetylaminofluorene
-
-
?
additional information
?
-
-
potent and selective induction by trans-stilbene oxide
-
-
?
additional information
?
-
-
the enzyme activity in diabetic and in fasted rats is reduced by 60-71%, key enzyme in the metabolism of environmental contaminants being responsible for xenobiotic transformations, regulation of the enzyme occurs at transcriptional, translational, and post-translational level, the enzyme is also involved in cytoprotection and steroid metabolism, as well as in cellular responses to glucose metabolism and in Na+-dependent bile acid transport, the enzyme is part of a multi-transport system at the cell surface
-
-
?
additional information
?
-
-
the enzyme is critical for biotransformations in xenobiotic metabolism and detoxification
-
-
?
additional information
?
-
-
the enzyme is involved in xenobiotic metabolism and detoxification, e.g. of 1,3-butadiene oxide, styrene oxide, and benzo[a]pyrene-4,5-oxide
-
-
?
additional information
?
-
-
the enzyme metabolizes xenobiotic epoxides
-
-
?
additional information
?
-
-
enantioselectivity with fatty acid epoxide substrates
-
-
?
additional information
?
-
-
mEH prefers mono- and cis-substituted epoxides, low but highly enantioselective activity with epoxy fatty acids, the enzyme acts as an antiestrogen binding site subunit
-
-
?
additional information
?
-
-
no activity with 5,6alpha-epoxy-5alpha-cholestan-3beta-ol and 5,6beta-epoxy-5alpha-cholestan-3beta-ol
-
-
?
additional information
?
-
-
substrate specificity, no activity with 1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene,i.e. HEOM, 2-acetylaminofluorene, arochlor 1254, and benzopyrene 4,5-oxide, the cytosolic enzyme hydrates epoxides on cyclic sytems very slowly, but hydrates a wide variety of aliphatic epoxides rapidly, trisubstituted terpenoid epoxides show low Km-values, fatty acid and ester epoxides are hydrated very quickly
-
-
?
additional information
?
-
-
the enzyme is distinct from the microsomal epoxide hydrolase EC 3.3.2.11, which specifically utilizes 5,6alpha-epoxy-5alpha-cholestan-3beta-ol, that is no substrate for EC 3.3.2.9
-
-
?
additional information
?
-
-
the enzyme shows a broad substrate specificity, all epoxides with a trisubstituted oxirane ring are no or poor substrates, no activity with 5,6alpha-epoxy-5alpha-cholestan-3beta-ol
-
-
?
additional information
?
-
-
wide substrate specificity, the enzyme prefers mono- and cis-1,2-disubstituted epoxides as substrates, while gem-di-, trans-di-, tri- and tetra-substituted epoxides are either low turnover substrates or inhibitors
-
-
?
additional information
?
-
-
not active with trans-1,3-diphenylpropene oxide
-
-
?
additional information
?
-
microsomal epoxide hydrolase (mEH) has wide a substrate specificity
-
-
?
additional information
?
-
microsomal epoxide hydrolase (mEH) has wide a substrate specificity
-
-
?
additional information
?
-
-
enantioselectivity with fatty acid epoxide substrates
-
-
?
additional information
?
-
-
enantioselectivity with fatty acid epoxide substrates
-
-
?
additional information
?
-
-
induced about threefold by 5 mM phenobarbital
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O
(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid
(5Z,8Z,11Z)-14,15-epoxyeicosa-5,8,11-trienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosa-5,8,11-trienoic acid
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O
(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid
7,12-dimethylbenz[a]anthracene + 3 H2O
7,12-dimethylbenz[a]anthra-3,4-diol-1,2-epoxide
-
-
-
?
7,12-dimethylbenz[a]anthracene + 3 H2O
7,12-dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide
-
-
-
?
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O
(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O
(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid
-
-
-
-
?
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O
(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid
-
-
-
-
?
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O
(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid
-
-
-
-
?
16,17-epoxyandrost-4-en-3-one + H2O
16,17-dihydroxyandrost-4-en-3-one
-
high activity
-
-
?
16,17-epoxyandrost-4-en-3-one + H2O
16,17-dihydroxyandrost-4-en-3-one
-
high activity
-
-
?
16,17-epoxyandrost-4-en-3-one + H2O
16,17-dihydroxyandrost-4-en-3-one
-
high activity
-
-
?
4-vinylcyclohexene diepoxide + H2O
4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane
-
-
-
?
4-vinylcyclohexene diepoxide + H2O
4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane
-
-
-
?
4-vinylcyclohexene diepoxide + H2O
4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane
-
-
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
?
additional information
?
-
-
enzyme is induced by a number of xenobiotics, the enzyme is thought to play a detoxifying role by preventing epoxides from reacting irreversibly with critical cellular macromolecules. Some evidence exists to support the hypothesis that microsomal epoxide hydrolase is closely associated with at least certain forms of cytochrome P-450, such association may influence the functional role of the microsomal epoxide hydrolase in the various pathways of bioactivation
-
-
?
additional information
?
-
the enzyme in Drosophila melanogaster is involved in xenobiotic biotransformation, but not in juvenile hormone metabolism
-
-
?
additional information
?
-
-
the enzyme in Drosophila melanogaster is involved in xenobiotic biotransformation, but not in juvenile hormone metabolism
-
-
?
additional information
?
-
-
enzyme is induced by a number of xenobiotics, the enzyme is thought to play a detoxifying role by preventing epoxides from reacting irreversibly with critical cellular macromolecules. Some evidence exists to support the hypothesis that microsomal epoxide hydrolase is closely associated with at least certain forms of cytochrome P-450, such association may influence the functional role of the microsomal epoxide hydrolase in the various pathways of bioactivation
-
-
?
additional information
?
-
-
involved in the biotransformation of epoxides produced from either xeno- or endobiotics. The diols produced are generally detoxification products but in several instances, such as 9,10-epoxybenzopyrene-7,8-diol, they are very potent mutagens and possible carcinogens. The enzyme is induced by phenobarbital
-
-
?
additional information
?
-
-
the enzyme is expected to play a purely protective role with respect to epoxides metabolically produced from pharmaceutical drugs
-
-
?
additional information
?
-
-
genetic polymorphisms of the enzyme are responsible for varying susceptibility of cigarette smoking humans to chronic obstructive pulmonary disease, COPD
-
-
?
additional information
?
-
-
key enzyme in the metabolism of environmental contaminants being responsible for xenobiotic transformations, regulation of the enzyme occurs at transcriptional, translational, and post-translational level, the enzyme is also involved in cytoprotection and steroid metabolism, as well as in cellular responses to glucose metabolism and in Na+-dependent bile acid transport, the enzyme is part of a multi-transport system at the cell surface
-
-
?
additional information
?
-
-
the enzyme is a phase II biotransformation enzyme which detoxifies epoxides, including carcinogens such as polycyclic aromatic hydrocarbons found in cigarette smoke and cooked meats, enzyme polymorphisms are not associated with colon cancer risk
-
-
?
additional information
?
-
-
the enzyme is critical for biotransformations in xenobiotic metabolism and detoxification
-
-
?
additional information
?
-
-
the enzyme is involved in xenobiotic metabolism and detoxification, e.g. of 1,3-butadiene oxide, styrene oxide, and benzo[a]pyrene-4,5-oxide, enzyme deficiency leads to acute and severe phenytoin toxicity in vivo, the enzyme is involved in transport of bile acids in the liver
-
-
?
additional information
?
-
-
EPHX1 detoxifies genotoxic compounds and participates in the removal of reactive oxygen species
-
-
?
additional information
?
-
-
mEH is capable of inactivating a large number of structurally different, highly reactive epoxides and hence is an important part of the enzymatic defence of our organism against adverse effects of foreign compounds
-
-
?
additional information
?
-
-
mEH mediates the transport of bile acid in the liver
-
-
?
additional information
?
-
enzyme mEH in collaboration with cytochrome-P-450 (CYP) converts benzo(a)pyrene to more reactive intermediate, benzo(a)pyrene-7,8-dihydrodiol 8,9-epoxide (benzo(a)pyrene diolepoxide, BPDE) which displays higher mutagenic and carcinogenic potential than its substrate
-
-
?
additional information
?
-
-
enzyme mEH in collaboration with cytochrome-P-450 (CYP) converts benzo(a)pyrene to more reactive intermediate, benzo(a)pyrene-7,8-dihydrodiol 8,9-epoxide (benzo(a)pyrene diolepoxide, BPDE) which displays higher mutagenic and carcinogenic potential than its substrate
-
-
?
additional information
?
-
oxetanes are a nonepoxide class of substrates for human mEH, which is known to catalyze the hydrolytic ring opening of electrophilic and potentially toxic epoxide-containing drugs, drug metabolites, and exogenous organochemicals
-
-
?
additional information
?
-
-
oxetanes are a nonepoxide class of substrates for human mEH, which is known to catalyze the hydrolytic ring opening of electrophilic and potentially toxic epoxide-containing drugs, drug metabolites, and exogenous organochemicals
-
-
?
additional information
?
-
the enzyme converts epoxides to diols and is able to either detoxify or bioactivate a wide range of substrates. The prototypical EPHX1 reaction involves conversion of epoxides to trans-dihydrodiols. EPHX1 more readily converts xenobiotics than endogenous substrates
-
-
?
additional information
?
-
-
the enzyme converts epoxides to diols and is able to either detoxify or bioactivate a wide range of substrates. The prototypical EPHX1 reaction involves conversion of epoxides to trans-dihydrodiols. EPHX1 more readily converts xenobiotics than endogenous substrates
-
-
?
additional information
?
-
-
the enzyme may play a significant role in the secondary metabolism of juvenile hormone acid generated by juvenile hormone esterase
-
-
?
additional information
?
-
-
enzyme is induced by a number of xenobiotics, the enzyme is thought to play a detoxifying role by preventing epoxides from reacting irreversibly with critical cellular macromolecules. Some evidence exists to support the hypothesis that microsomal epoxide hydrolase is closely associated with at least certain forms of cytochrome P-450, such association may influence the functional role of the microsomal epoxide hydrolase in the various pathways of bioactivation
-
-
?
additional information
?
-
-
the enzyme plays an important role in the metabolism of various xenobiotic compounds including the polycyclic aromatic hydrocarbon carcinogens. It is specifically involved in the formation of the ultimate carcinogen of benzopyrene
-
-
?
additional information
?
-
-
probably represents an important factor in the control of reactive epoxides
-
-
?
additional information
?
-
-
key enzyme in the metabolism of environmental contaminants being responsible for xenobiotic transformations, regulation of the enzyme occurs at transcriptional, translational, and post-translational level. The enzyme is also involved in cytoprotection and steroid metabolism, as well as in cellular responses to glucose metabolism and in Na+-dependent bile acid transport. The enzyme is part of a multi-transport system at the cell surface
-
-
?
additional information
?
-
-
the enzyme is involved in xenobiotic metabolism and detoxification, e.g. of 1,3-butadiene oxide, styrene oxide, and benzo[a]pyrene-4,5-oxide, the enzyme is important in sexual development
-
-
?
additional information
?
-
-
mEH is capable of inactivating a large number of structurally different, highly reactive epoxides and hence is an important part of the enzymatic defence of our organism against adverse effects of foreign compounds
-
-
?
additional information
?
-
-
mEH mediates the transport of bile acid in the liver
-
-
?
additional information
?
-
stereoselective hydrolysis of epoxyeicosatrienoic acids (EETs) by sEH
-
-
?
additional information
?
-
-
enzyme is induced by a number of xenobiotics, the enzyme is thought to play a detoxifying role by preventing epoxides from reacting irreversibly with critical cellular macromolecules. Some evidence exists to support the hypothesis that microsomal epoxide hydrolase is closely associated with at least certain forms of cytochrome P-450, such association may influence the functional role of the microsomal epoxide hydrolase in the various pathways of bioactivation
-
-
?
additional information
?
-
-
role in benzopyrene-induced mutagenesis and carcinogenesis
-
-
?
additional information
?
-
-
enzyme is involved in the metabolism of steroids, the microsomal enzyme plays a central role in both the inactivation of primary mutagenic and carcinogenic metabolites of polycyclic aromatic hydrocarbons, and in activating these metabolites to even more toxic or mutagenic secondary products, enzyme production is induced by 3-methylcholanthrene, phenobarbital, trans-stilbene oxide, 2(3)-tert-butyl-4-hydroxyanisol or 2-acetylaminofluorene
-
-
?
additional information
?
-
-
potent and selective induction by trans-stilbene oxide
-
-
?
additional information
?
-
-
the enzyme activity in diabetic and in fasted rats is reduced by 60-71%, key enzyme in the metabolism of environmental contaminants being responsible for xenobiotic transformations, regulation of the enzyme occurs at transcriptional, translational, and post-translational level, the enzyme is also involved in cytoprotection and steroid metabolism, as well as in cellular responses to glucose metabolism and in Na+-dependent bile acid transport, the enzyme is part of a multi-transport system at the cell surface
-
-
?
additional information
?
-
-
the enzyme is critical for biotransformations in xenobiotic metabolism and detoxification
-
-
?
additional information
?
-
-
the enzyme is involved in xenobiotic metabolism and detoxification, e.g. of 1,3-butadiene oxide, styrene oxide, and benzo[a]pyrene-4,5-oxide
-
-
?
additional information
?
-
-
the enzyme metabolizes xenobiotic epoxides
-
-
?
additional information
?
-
-
induced about threefold by 5 mM phenobarbital
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Al3+
Ba2+
Ca2+
Cd2+
Co2+
Cu2+
Fe2+
Fe3+
Hg2+
Mg2+
Mn2+
Ni2+
Pb2+
Zn2+
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2R,3R)-1-benzyloxy-2,3-epoxy-3-(4-nitrophenyl)propane
-
9.0% inhibition at 0.1 mM
(2S,3S)-1-benzyloxy-2,3-epoxy-3-(4-nitrophenyl)propane
-
11% inhibition at 0.1 mM
(S)-1-(1-phenylethyl)-3-(3-phenylpropyl)urea
15.4% inhibition at 0.01 mM
Lipid
-
above the critrical micelle concentration gives kinetic pattern that mimics competitive inhibition
Metyrapone
-
strong inhibition of hydration of benzopyrene 11,12-oxide and dibenzoanthracene 5,6-oxide
trans-stilbene oxide
-
inhibits hydration of estroxide, androstene oxide and styrene 7,8-oxide
Cyclohexene oxide
-
inhibits hydration of estroxide, androstene oxide and styrene 7,8-oxide
Cyclohexene oxide
using a post-natal day 4 Fischer 344 rat whole ovary culture system, inhibition of mEH using cyclohexene oxide during 4-vinylcyclohexene exposure results in a greater loss of primordial and small primary follicles relative to 4-vinylcyclohexene-treated ovaries. Also, relative to controls, mEH mRNA is increased on day 4 of 4-vinylcyclohexene exposure, followed by increased mEH protein after 6 days. Inhibition of PI3K signaling increases mEH mRNA and protein expression
Cyclohexene oxide
a post-natal day 4 Fischer 344 rat whole ovary culture system inhibition of mEH using cyclohexene oxide during VCD exposure results in a greater loss of primordial and small primary follicles relative to VCD-treated ovaries
elaidamide
-
most potent inhibitor, has a mix of competitive and non-competitive inhibition kinetics
elaidamide
-
most potent inhibitor, has a mix of competitive and non-competitive inhibition kinetics
trichloropropene oxide
-
inhibits hydration of estroxide, androstene oxide and styrene 7,8-oxide
additional information
HNF3 negatively regulates the transactivation of E1 promoter by GATA-4 in hepatoma cells
-
additional information
-
HNF3 negatively regulates the transactivation of E1 promoter by GATA-4 in hepatoma cells
-
additional information
-
suppression of enzyme expression by glucocorticoid, interacting with the 5'-flanking sequence, and by dexamethasone, gadolinium chloride, acriflavine, lipopolysaccharide, gem-di-, trans-di-, tri- and tetra-substituted epoxides are either low turnover substrates or inhibitors
-
additional information
-
quantitative structure-activity relationships in epoxides inhibiting EH activity, molecular modelling, kinetics, overview
-
additional information
-
metal chelators like 1,10-phenanthroline, 1,7-phenanthroline, EDTA, EGTA, and dipicolinic acid preserve enzyme activity in presence of metal ions
-
additional information
-
not inhibited by trans-4-[4-(1-adamantylcarbamoylamino)cyclohexyloxy] benzoic acid
-
additional information
-
no inhibition by cis-2,3-epoxybutane and 2,3-dimethyl-2,3-epoxybutane
-
additional information
-
no inhibition by 3-phenylglycidol enantiomers, inhibitor synthesis, overview, inhibition mechanisms, overview
-
additional information
-
no inhibition by Co2+ at 1 mM, metal chelators like 1,10-phenanthroline, 1,7-phenanthroline, EDTA, EGTA, and dipicolinic acid preserve enzyme activity in presence of metal ions
-
additional information
-
no inhibition by 5,6alpha-imino-5alpha-cholestane-3beta-ol
-
additional information
enantioselective urea inhibitors of soluble epoxide hydrolase (sEH, EC 3.3.2.9) have mostly no inhibitory effect on the microsomal epoxide hydrolase, mEH, some are slightly activating for mEH. No inhibition by 12-[[(tricyclo[3.3.1.13,7]dec-1-ylamino)carbonyl]amino]-dodecanoic acid (AUDA)
-
additional information
-
5,6alpha-epoxy-5alpha-cholestan-3beta-ol causes down-regulation of the enzyme, no effect by cholestyramine and clofibrate
-
additional information
-
no inhibition by 5,6alpha-imino-5alpha-cholestane-3beta-ol
-
additional information
-
no inhibition by isoquinoline, 7-oxocholesterol, 7-oxocholestanol, and 6-oxocholestanol
-
additional information
-
suppression of enzyme expression by dexamethasone, gadolinium chloride, acriflavine, lipopolysaccharide
-
additional information
-
metal chelators like 1,10-phenanthroline, 1,7-phenanthroline, EDTA, EGTA, and dipicolinic acid preserve enzyme activity in presence of metal ions
-
additional information
not inhibitory: 3-octylthio-1,1,1-trifluoro-2-propanone; not inhibitory: 3-octylthio-1,1,1-trifluoro-2-propanone; not inhibitory: 3-octylthio-1,1,1-trifluoro-2-propanone
-
additional information
not inhibitory: 3-octylthio-1,1,1-trifluoro-2-propanone; not inhibitory: 3-octylthio-1,1,1-trifluoro-2-propanone; not inhibitory: 3-octylthio-1,1,1-trifluoro-2-propanone
-
additional information
not inhibitory: 3-octylthio-1,1,1-trifluoro-2-propanone; not inhibitory: 3-octylthio-1,1,1-trifluoro-2-propanone; not inhibitory: 3-octylthio-1,1,1-trifluoro-2-propanone
-
additional information
-
not inhibitory: 3-octylthio-1,1,1-trifluoro-2-propanone; not inhibitory: 3-octylthio-1,1,1-trifluoro-2-propanone; not inhibitory: 3-octylthio-1,1,1-trifluoro-2-propanone
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(R)-1-(2,3-dihydro-1H-inden-1-yl)-3-(3-phenylpropyl)urea
10% activation at 0.01 mM
(R)-1-(2-hydroxy-1-phenylethyl)-3-(3-phenylpropyl)urea
7% activation at 0.01 mM
(R)-1-(3-phenylpropyl)-3-(1,2,3,4-tetrahydronaphthalen-1-yl)urea
6% activation at 0.01 mM
(S)-1-(1-phenylpropyl)-3-(3-phenylpropyl)urea
6% activation at 0.01 mM
(S)-1-(2,3-dihydro-1H-inden-1-yl)-3-(3-phenylpropyl)urea
12% activation at 0.01 mM
(S)-1-(3-phenylpropyl)-3-(1,2,3,4-tetrahydronaphthalen-1-yl)urea
6% activation at 0.01 mM
3-methylcholanthrene
-
enhances nuclear hydration of phenanthrene-9,10-oxide, benzopyrene-11,12-oxide and octene-1,2-oxide, no significant effect on microsomal hydration
CHAPS
-
stimulates, increases the enantiomeric ratio of activity with R-enantiomer to S-enantiomer of 1,2-epoxyhexane and styrene oxide
cytochrome P450
-
activation of microsomal epoxide hydrolase by interaction with cytochromes P450
-
Digitonin
-
stimulates, increases the enantiomeric ratio of activity with R-enantiomer to S-enantiomer of 1,2-epoxyhexane and styrene oxide
dodecyl maltoside
-
stimulates, increases the enantiomeric ratio of activity with R-enantiomer to S-enantiomer of 1,2-epoxyhexane and styrene oxide
erucin
-
exposure of liver slices to erucin results in elevated glucuronosyl transferase and epoxide hydrolase activities and expression
glucoerucin
-
exposure of liver slices to glucoerucin causes a marked increase in the activity and expression of the microsomal epoxide hydrolase but has no effect on glucuronosyl transferase activity
glucoraphanin
-
exposure of liver slices to glucoraphanin causes a marked increase in the activity and expression of the microsomal epoxide hydrolase but has no effect on glucuronosyl transferase activity
octyl-glucoside
-
stimulates, increases the enantiomeric ratio of activity with R-enantiomer to S-enantiomer of 1,2-epoxyhexane and styrene oxide
phenethyl isothiocyanate
-
exposure of liver slices to phenethyl isothiocyanate results in elevated glucuronosyl transferase and epoxide hydrolase activities and expression
Phenobarbital
-
enhances nuclear and microsomal hydration of phenanthrene-9,10-oxide, benzopyrene-11,12-oxide and octene-1,2-oxide
R-sulforaphane
-
exposure of liver slices to R-sulforaphane causes a marked increase in the activity and expression of the microsomal epoxide hydrolase
sucrose monolaurate
-
stimulates, increases the enantiomeric ratio of activity with R-enantiomer to S-enantiomer of 1,2-epoxyhexane and styrene oxide
Thesit
-
stimulates, increases the enantiomeric ratio of activity with R-enantiomer to S-enantiomer of 1,2-epoxyhexane and styrene oxide
-
Zwittergent 3-12
-
stimulates, increases the enantiomeric ratio of activity with R-enantiomer to S-enantiomer of 1,2-epoxyhexane and styrene oxide
hepatitis B spliced protein
enhances hydrolysis activity of microsomal epoxide hydrolase
-
hepatitis B spliced protein
-
enhances hydrolysis activity of microsomal epoxide hydrolase
-
Metyrapone
-
great stimulation of hydration of styrene 7,8-oxide and octene 1,2-oxide, slight stimulation of hydration of benzopyrane 4,5-oxide
additional information
-
enzyme expression is induced by exogenous beta-amyloid and trimethyl-tin, a neurotoxic agent, beta-amyloid aggregation induces enzyme expression in astrocytes
-
additional information
-
induction of the enzyme by clofibrate and di(2-ethylhexyl)phthalate
-
additional information
-
benzo[a]pyrene, dibenzo[a,h]anthracene and fluoranthene give rise to a statistically significant increase in epoxide hydrolase activity, which is accompanied by a concomitant increase in epoxide hydrolase protein levels, dibenzo[a,l]pyrene, benzo[b]fluoranthene and 1-methylphenanthrene, influence neither activity nor enzyme protein levels
-
additional information
minimally altering the structural elements in the immediate vicinity of the oxetane can greatly modulate the efficiency of hydrolytic ring cleavage. In particular, higher pKa in the vicinity of the oxetane and an increased distance between the oxetane ring and the benzylic nitrogen improve reaction rate, which is further enhanced by the presence of methyl groups near or on the oxetane
-
additional information
-
minimally altering the structural elements in the immediate vicinity of the oxetane can greatly modulate the efficiency of hydrolytic ring cleavage. In particular, higher pKa in the vicinity of the oxetane and an increased distance between the oxetane ring and the benzylic nitrogen improve reaction rate, which is further enhanced by the presence of methyl groups near or on the oxetane
-
additional information
substituted imidazole, metyrapone, and ethanol activate EPHX1 in vitro
-
additional information
-
substituted imidazole, metyrapone, and ethanol activate EPHX1 in vitro
-
additional information
-
induction of the enzyme by clofibrate and di(2-ethylhexyl)phthalate
-
additional information
-
induction of the enzyme by clofibrate and di(2-ethylhexyl)phthalate
-
additional information
-
4-vinylcyclohexene diepoxide (0.005 mM) causes an increase in mEH mRNA by 0.5fold at day 10
-
additional information
-
increased expression of mEH mRNA is detected after 4 days of 4-vinylcyclohexene diepoxide exposure
-
additional information
-
mEH expression is up-regulated after 1-methyl-4-phemyl-1,2,3,6-tetrahydropyridine intoxication
-
additional information
-
induction of the enzyme by clofibrate and di(2-ethylhexyl)phthalate
-
additional information
-
maximal activity with dimethyl formamide as co-solvent, effects of solvents on enzyme activity, overview
-
additional information
-
enzyme expression is induced by neurotoxic agent trimethyl-tin in hippocampus and entorhinal cortex
-
additional information
-
induction of the enzyme by clofibrate and di(2-ethylhexyl)phthalate
-
additional information
-
insulin increases enzyme activity in hepatocyte cell culture
-
additional information
-
no effect by cholestyramine and clofibrate, phenobarbital and isosafrole induce the enzyme expression, it is also induced by trans-stilbene oxide, gamma-chlordane, Aroclor 1254, and 2-acetylamineo-fluorene in liver microsomes
-
additional information
-
benzo[a]pyrene, dibenzo[a,h]anthracene and fluoranthene give rise to a statistically significant increase in epoxide hydrolase activity, which is accompanied by a concomitant increase in epoxide hydrolase protein levels, dibenzo[a,l]pyrene, benzo[b]fluoranthene and 1-methylphenanthrene, influence neither activity nor enzyme protein levels
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.542
(3-(4-(2-oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-ethoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone
-
at pH 7.4 and 37°C
0.352
1-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]methanamine
pH 7.4, 37°C, liver microsomes
0.027 - 0.067
[3-[4-([((3-methyloxetan-3-yl)methyl)amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone
0.028 - 0.089
[3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone
0.05 - 0.051
[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone
0.026 - 0.047
[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone
0.139
2-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]ethan-1-amine
pH 7.4, 37°C, liver microsomes
0.684
2-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]ethan-1-amine
pH 7.4, 37°C, recombinant enzyme
0.022
4-methyl-2-oxo-2H-chromen-7-yl oxiran-2-ylmethyl carbonate
-
pH 9.0, 37°C
0.0023
cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate
-
pH 9.0, 37°C
0.0032
juvenile hormone III
in 100 mM sodium phosphate, pH 8.0, at 30°C
0.027
[3-[4-([((3-methyloxetan-3-yl)methyl)amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone
pH 7.4, 37°C, liver microsomes
0.067
[3-[4-([((3-methyloxetan-3-yl)methyl)amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone
pH 7.4, 37°C, recombinant enzyme
0.028
[3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone
pH 7.4, 37°C, liver microsomes
0.089
[3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone
pH 7.4, 37°C, recombinant enzyme
0.05
[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone
pH 7.4, 37°C, recombinant enzyme
0.051
[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone
pH 7.4, 37°C, liver microsomes
0.026
[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone
pH 7.4, 37°C, liver microsomes
0.047
[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone
pH 7.4, 37°C, recombinant enzyme
additional information
additional information
Michaelis-Menten-type kinetics for native (using liver microsomes) and recombinant enzymes with different substrates
-
additional information
additional information
-
Michaelis-Menten-type kinetics for native (using liver microsomes) and recombinant enzymes with different substrates
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.002
juvenile hormone III
in 100 mM sodium phosphate, pH 8.0, at 30°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
630
juvenile hormone III
in 100 mM sodium phosphate, pH 8.0, at 30°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000072
2-nonylsulfanyl-propionamide
-
in Tris/HCl buffer (0.1 M, pH 9.0), at 30°C
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00016
1,3-dicyclohexylurea
Homo sapiens
-
pH and temperature not specified in the publication
0.00235
N-(phenylcarbamothioyl)acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00129
N-(phenylcarbamothioyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00207
N-(pyridin-4-ylcarbamothioyl)acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00228
N-(pyridin-4-ylcarbamothioyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0027
N-(tert-butylcarbamothioyl)acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00158
N-(tert-butylcarbamothioyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00112
N-acetyl-N'-adamantyl thiourea
Homo sapiens
-
pH and temperature not specified in the publication
0.00139
N-acetyl-N'-[(3-trifluoromethyl-4-bromo)phenyl] thiourea
Homo sapiens
-
pH and temperature not specified in the publication
0.00101
N-benzoyl-N'-adamantyl thiourea
Homo sapiens
-
pH and temperature not specified in the publication
0.00117
N-benzoyl-N'-[(3-trifluoromethyl-4-bromo)phenyl] thiourea
Homo sapiens
-
pH and temperature not specified in the publication
0.00229
N-[(2,6-dichlorophenyl)carbamothioyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00215
N-[(2,6-dichlorophenyl)carbamothioyl]benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00253
N-[(2,6-diethoxyphenyl)carbamothioyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00204
N-[(2,6-diethoxyphenyl)carbamothioyl]benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00169
N-[(2-methoxy-4-methylphenyl)carbamothioyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00254
N-[(2-methoxy-4-methylphenyl)carbamothioyl]benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00187
N-[(2-methoxy-4-nitrophenyl)carbamothioyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00165
N-[(2-methoxy-4-nitrophenyl)carbamothioyl]benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0015
N-[(2-methylphenyl)carbamothioyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00354
N-[(2-methylphenyl)carbamothioyl]benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00242
N-[(4-bromonaphthalen-1-yl)carbamothioyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00188
N-[(4-bromonaphthalen-1-yl)carbamothioyl]benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00164
N-[(4-bromophenyl)carbamothioyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00344
N-[(4-bromophenyl)carbamothioyl]benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00221
N-[(4-chlorophenyl)carbamothioyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00164
N-[(4-chlorophenyl)carbamothioyl]benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0037
N-[(4-phenoxyphenyl)carbamothioyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0021
N-[(4-phenoxyphenyl)carbamothioyl]benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00259
N-[[4-(morpholin-4-yl)phenyl]carbamothioyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00172
N-[[4-(morpholin-4-yl)phenyl]carbamothioyl]benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.063
(9E)-octadec-9-enamide
Rattus norvegicus
-
substrate cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate, pH 9.0, 37°C
0.14
(9E)-octadec-9-enamide
Homo sapiens
-
substrate cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate, pH 9.0, 37°C
0.0011
12-hydroxyoctadecanamide
Rattus norvegicus
-
substrate cis-stilbene oxide, pH 9.0, 37°C
0.123
12-hydroxyoctadecanamide
Rattus norvegicus
-
substrate cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate, pH 9.0, 37°C
0.2
12-hydroxyoctadecanamide
Homo sapiens
-
or above, substrate cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate, pH 9.0, 37°C
0.0004
2-(nonylsulfanyl)propanamide
Rattus norvegicus
-
substrate cis-stilbene oxide, pH 9.0, 37°C
0.0005
2-(nonylsulfanyl)propanamide
Homo sapiens
-
substrate cis-stilbene oxide, pH 9.0, 37°C
0.0042
2-(nonylsulfanyl)propanamide
Rattus norvegicus
-
substrate cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate, pH 9.0, 37°C
0.006
2-(nonylsulfanyl)propanamide
Homo sapiens
-
substrate cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate, pH 9.0, 37°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00003
with cyano(6-methoxy-naphthalen-2-yl)methyl oxiran-2-ylmethyl carbonate as substrate, in 100 mM sodium phosphate, pH 8.0, at 30°C
0.0001
with trans-diphenylpropene oxide as substrate, in 100 mM sodium phosphate, pH 8.0, at 30°C
0.00019
0.0003
with trans-stilbene oxide as substrate, in 100 mM sodium phosphate, pH 8.0, at 30°C
0.00036
with 14,15-epoxyeicosatrienoic acid as substrate, at pH 8.0 and 30°C
0.0013
with trans-diphenylpropene oxide as substrate, at pH 7.0 and 30°C
0.0017
with juvenile hormone III as substrate, in 100 mM sodium phosphate, pH 8.0, at 30°C
0.0037
with cyano-(6-methoxy-naphthalen-2-yl)-methyl 3,3-dimethyl-oxiranylmethyl carbonate as substrate, in 100 mM sodium phosphate, pH 8.0, at 30°C
0.021
-
substrate 4-methyl-2-oxo-2H-chromen-7-yl oxiran-2-ylmethyl carbonate, pH 9.0, 37°C
0.025
-
substrate cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate, pH 9.0, 37°C
0.029
-
substrate 4-nitrophenyl 6-oxabicyclo[3.1.0]hexane-3-carboxylate, pH 9.0, 37°C
0.0293
with juvenile hormone III as substrate, at pH 8.0 and 30°C
0.0458
with cis-stilbene oxide as substrate, in 100 mM sodium phosphate, pH 8.0, at 30°C
0.0475
with cis-stilbene oxide as substrate, at pH 7.0 and 30°C
0.048
-
substrate 4-methyl-2-oxo-2H-chromen-7-yl oxiran-2-ylmethyl carbonate, pH 9.0, 37°C
0.051
-
substrate 4-nitrophenyl 6-oxabicyclo[3.1.0]hexane-3-carboxylate, pH 9.0, 37°C
0.068
-
substrate cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate, pH 9.0, 37°C
0.122
with cyano-(6-methoxy-naphthalen-2-yl)-methyl trans-((3-ethyl-oxiran-2-yl)methyl) carbonate as substrate, in 100 mM sodium phosphate, pH 8.0, at 30°C
0.138
with cyano(2-methoxynaphthalen-6-yl)methyl trans-(2-(3-phenyloxiran-2-yl))acetate as substrate, in 100 mM sodium phosphate, pH 8.0, at 30°C
0.816
with cyano(6-methoxy-naphthalen-2-yl)methyl trans-[(3-phenyloxiran-2-yl)methyl]carbonate as substrate, in 100 mM sodium phosphate, pH 8.0, at 30°C
1.18
with cyano(2-methoxynaphthalen-6-yl)methyl trans-2-(3-propyloxiran-2-yl)acetate as substrate, in 100 mM sodium phosphate, pH 8.0, at 30°C
additional information
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.7
-
cytosolic and microsomal enzyme, hydration of trans-beta-ethylstyrene oxide
7.4
7.4 - 9
8 - 9
8.9
9.4
-
somewhat higher than, hydration of styrene oxide in glycine buffer
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5 - 9.8
-
pH 6.5: about 50% of maximal activity, pH 9.8: about 55% of maximal activity
7 - 10
-
pH 7.0: about 60% of maximal activity, pH 10.0: about 25% of maximal activity
7 - 9.5
-
pH 7.0: about 35% of maximal activity, pH 9.5: about 70% of maximal activity
7.4 - 9
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
26
30
37
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
208877, 208879, 208881, 208884, 208893, 208895, 208900, 208901, 208909, 208911, 208915, 660713, 661418, 661419, 663275, 663432, 663434, 683516, 692205, 695932, 695933, 696572, 697480, 697577, 698150, 699759, 699956, 700328, 700555, 700587, 701185, 701302, 713743
-
-
brenda
isoform EPHX1, patients with a first acute non-fatal myocardial infarction
-
-
brenda
-
208877, 208880, 208881, 208889, 208896, 208901, 208903, 208907, 208911, 660713, 660845, 663275, 684089, 695933, 696572, 699680, 700587, 701301, 701319, 709622, 716954, 731547
-
-
brenda
-
208877, 208878, 208879, 208880, 208884, 208885, 208886, 208887, 208888, 208890, 208892, 208893, 208894, 208895, 208896, 208897, 208899, 208901, 208908, 208915, 208919, 654344, 654503, 657394, 660713, 661476, 663275, 683503, 697312, 699685, 700328, 713743, 713997, 716954
-
-
brenda
enzyme activity is about 2.5 to 3 times higher in male than in female
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
hypophysectomy induces the liver enzyme in females and males
brenda
-
regulation of mEH during the menstrual cycle: during the first half mEH expression is low, increases during the second half and reaches highest levels during pregnancy, immunohistochemical analysis, overview
brenda
additional information
-
mEH distribution, immunohistochemical analysis, overview. mEH immunoreactivity is present in specific neuronal populations of the hippocampus, striatum, amygdala, and cerebellum, as well as in a fraction of astrocytes
brenda
-
mEH distribution, immunohistochemical analysis, overview. mEH immunoreactivity is present in specific neuronal populations of the hippocampus, striatum, amygdala, and cerebellum, as well as in a fraction of astrocytes
-
brenda
-
glial cell culture, enzyme expression is elevated in hippocampus and associated cortex of patients with Alzheimer's disease
brenda
-
-
208879, 208881, 208884, 208893, 208895, 208900, 208901, 208915, 660713, 663275, 663434, 697577, 700328, 708309, 732444, 732905, 736011
brenda
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both the E1 and the E1-b EPHX1 transcripts are detected at high levels in the liver although E1-b is the major hepatic transcript, accounting for about 70% of the total EPHX1 RNA expressed in this tissue
brenda
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208880, 208881, 208889, 208896, 208901, 208903, 208907, 660713, 660845, 661024, 663275, 663434, 731547
brenda
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208878, 208879, 208880, 208881, 208884, 208885, 208886, 208887, 208888, 208890, 208892, 208893, 208895, 208896, 208897, 208899, 208901, 208908, 208915, 208919, 654344, 654503, 657394, 660713, 660782, 661435, 662084, 663434, 697312, 700328
brenda
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in the rat basal lung epoxide hydrolase activity is much lower than liver
brenda
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intra-epithelial, cells show down-regulated enzyme expression
brenda
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neonatal mouse ovarian culture system. Incubation of ovaries in presence of 7,12-dimethylbenz[a]anthracene. At 1 mM 7,12-dimethylbenz[a]anthracene, follicle loss and increased microsomal epoxide hydrolase protein are measured by 6 h. mRNA encoding epoxide hydrolase markedly increases after 2 days of incubation, and this increase precedes accelerated follicle loss at 4 days
brenda
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exposure to 4-vinylcyclohexene results in increased mRNA and protein expression of microsomal epoxide hydrolase, and an inactive tetrol metabolite 4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane can be formed in mouse ovarian follicles, potentially through detoxification action of mEH
brenda
using a post-natal day 4 Fischer 344 rat whole ovary culture system, inhibition of mEH using cyclohexene oxide during 4-vinylcyclohexene exposure results in a greater loss of primordial and small primary follicles relative to 4-vinylcyclohexene-treated ovaries. Also, relative to controls, mEH mRNA is increased on day 4 of 4-vinylcyclohexene exposure, followed by increased mEH protein after 6 days. Inhibition of PI3K signaling increases mEH mRNA and protein expression
brenda
post-natal day 4, both primordial and small primary follicles
brenda
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post-natal day 4, both primordial and small primary follicles
-
brenda
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the transcript of Ephx1 increases in the oviductal epithelium at the estrus stage and in day 3 of pregnancy
brenda
additional information
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wide tissue distribution in mammalian tissue, enzyme levels vary with environmental exposure, sex, and age
brenda
additional information
gene expression of EPHX1 in most tissues and anatomical compartments, by microarray, SAGE, and RNASeq, highest EPHX1 transcript and protein levels in liver and skin, high inter-individual variation among humans. Immunohistochemical EPHX1 protein staining
brenda
additional information
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gene expression of EPHX1 in most tissues and anatomical compartments, by microarray, SAGE, and RNASeq, highest EPHX1 transcript and protein levels in liver and skin, high inter-individual variation among humans. Immunohistochemical EPHX1 protein staining
brenda
additional information
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wide tissue distribution in mammalian tissue, enzyme levels vary with environmental exposure, sex, and age
brenda
additional information
microsomal epoxide hydrolase (mEH) is expressed in multiple tissues, including the ovary
brenda
additional information
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microsomal epoxide hydrolase (mEH) is expressed in multiple tissues, including the ovary
brenda
additional information
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wide tissue distribution in mammalian tissue, enzyme levels vary with environmental exposure, sex, and age, growth hormones are involved in sexually dimorphic liver enzyme expression
brenda
additional information
microsomal epoxide hydrolase (mEH) is expressed in multiple tissues, including the ovary
brenda
additional information
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microsomal epoxide hydrolase (mEH) is expressed in multiple tissues, including the ovary
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brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
type I enzyme form, microsomal epoxide hydrolase (mEH) is expressed on the hepatocyte endoplasmic reticulum membrane in two distinct topological orientations
brenda
additional information
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mEH is also associated with the nuclear and plasma membranes
brenda
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mEH is also associated with the nuclear and plasma membranes
brenda
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orientation of the enzyme depends on the membrane type
brenda
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brenda
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208879, 208881, 208884, 208893, 208895, 208900, 208901, 208909, 208911, 208915, 660713, 661418, 661419, 661658, 663275, 663432, 663434, 692205, 695932, 695933, 696572, 697480, 698150, 699759, 699956, 700328, 700555, 700587, 701302, 708203, 708309, 708408, 709573, 732299, 732444, 732905, 732940, 736011
brenda
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the N-terminal domains of mEHs are characterized by a microsomal domain which may or may not be preceded by an N-terminal membrane anchor, it is absent in the two Karenia brevis mEHs
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brenda
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208880, 208881, 208889, 208896, 208901, 208911, 660713, 660845, 661024, 663275, 663434, 695933, 696572, 699680, 700587, 701301, 701319, 709622, 710118, 731547
brenda
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208878, 208879, 208880, 208881, 208884, 208885, 208887, 208888, 208890, 208893, 208894, 208895, 208896, 208897, 208899, 208901, 208908, 208915, 208919, 654344, 657394, 660713, 660782, 661435, 661476, 661658, 662084, 663275, 663434, 697312, 700328, 716954
brenda
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slightly higher enzyme activity in smooth compared to rough microsomes
-
brenda
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in liver, the catalytic site facing the extracellular medium
brenda
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in liver, the catalytic site facing the cytosol
brenda
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mEH is mostly found attached to the smooth endoplasmic reticulum
brenda
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mEH is mostly found attached to the smooth endoplasmic reticulum
brenda
additional information
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the enzyme shows strong hydrophobic interaction with the membrane, deletion of the N-terminal membrane anchor does not render the enzyme soluble
-
brenda
additional information
the topology of EPHX1 on the cell surface greatly varies between different cell types
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brenda
additional information
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the topology of EPHX1 on the cell surface greatly varies between different cell types
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brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
enzymatic activity of mEH can be greatly increased by a point mutation E404D in the catalytic triad. But this variant is not found in any vertebrate species, despite the obvious advantage of accelerated detoxification. This evolutionary avoidance might be due to the fact that the mEH plays a dualistic role in detoxification and control of endogenous vascular signaling molecules. The critical role for mEH E404D in vasodynamics suggests that deregulation of endogenous signaling pathways is the undesirable gain of function associated with the E404D variant
evolution
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epoxide hydrolases of the alpha,beta-hydrolase type share significant homologies with other hydrolases, including esterases. The two Karenia brevis EHs are similar in that each has two active site Tyrs as well as a Glu located after beta7. Both of the alpha,beta fold type EHs identified in Karenia brevis belong to the mEH class. The lengths of the NC loops of the EHs are 36 and 43 residues, whereas both cap-loops are 14 residues. mEHs are characterized by having long to very long NC-loops (33 or more residues) and short to medium cap-loops. The Karenia brevis NC-loops and cap-loops are considered very long and medium in length, respectively. The length of these domains is believed to govern substrate selectivity of the EH and this combination of long/med NC-loop/cap-loop would suggest selectivity for aromatic epoxides. The EH1 appears to deviate from this generalization as selectivity is observed for aliphatic over aromatic substituted epoxides
evolution
microsomal epoxide hydrolase (EPHX1) is an evolutionarily highly conserved biotransformation enzyme for converting epoxides to diols. EPHX1 belongs to the family of alpha/beta hydrolases
malfunction
-
association of GSTT1 and GSTM1 null genotypes and mEPHX polymorphisms with hepatitis virus-related HCC risk in an Indian population
malfunction
-
genetically reduced EPHX1 activity is not a major risk factor for COPD and asthma, overview
malfunction
95% decrease in microsomal epoxide hydrolase expression levels is associated with a decrease in bile acid transport and severe hypercholanemia. EPHX1 transcription is significantly inhibited by two heterozygous mutations observed in the Old Order Amish population that present numerous hypercholanemic subjects in the absence of liver damage suggesting a defect in bile acid transport into the hepatocyte. High frequency of the H1.2 site polymorphism in the Amish population results in a potential genetic predisposition to hypercholanemia
malfunction
EPHX1 intron-1 heterozygous polymorphism in the human mEH gene (EPHX1) resulting in a 95% decrease in mEH expression. A patient exhibits a 100fold increase in serum bile acids in the absence of liver damage, suggesting a defect in transport while NTCP mRNA and protein expression levels are normal. EPHX1 intron-1 heterozygous polymorphism are previously described in a high percentage of the Lancaster County Old Order Amish population that present numerous hypercholanemic subjects without liver injury, suggesting the loss of transport capacity. No mutations have been detected in the NTCP gene from this population. The mEH intron-1 polymorphism results in a genetic predisposition for hypercholanemia and further supports the significant role of mEH in mediating hepatic sodium-dependent bile acid transport in concert with other transport mechanisms
malfunction
gene knockout mice models (Ephx1-null, mEH-/-) are fertile and have no phenotypic abnormalities, but a lack of bioactivation of 7,12-dimethylbenz[a]anthracene to the carcinogenic metabolite 3,4-diol-1,2-oxide. Disappearance of benzene-induced hematotoxicity and myelotoxicity in mEH-/- mice compared with the wild type ones
malfunction
mutations and polymorphic variants in the EPHX1 gene are associated with susceptibility to several human diseases including cancer. Mutations in EPHX1 may cause preeclampsia, hypercholanemia, and are suspected to contribute to fetal hydantoin syndrome and diphenylhydantoin toxicity. Japanese epilepsy patients carry an EPHX1 diplotype consisting of at least two His alleles in both rs1051740 and rs2234922. These patients show increased plasma carbamazepine-diol/carbamazepine-epoxide ratios. The rs2292566 single-nucleotide polymorphism (SNP) in EPHX1 may affect the maintenance dosage of the widely used anticoagulant warfarin. A significant association of the low EPHX1 activity diplotype harboring the rs1051740 and rs2234922 SNPs with alcohol dependence supports the role of EPHX1 genotype in the risk of alcoholic liver disease. Two non-synonymous EPHX1 SNPs (rs72549341 and rs148240980) are predicted by in silico models as breast cancer susceptibility modifiers. Low activity EPHX1 alleles harboring the rs1051740 SNP increases the risk of localized, but not advanced, prostate carcinoma. The rs1051740 His allele is significantly underrepresented in males with non-Hodgkin's lymphomas compared to healthy control individuals
metabolism
-
epoxide hydrolases comprise a family of enzymes important in detoxification and conversion of lipid signaling molecules, namely epoxyeicosatrienoic acids. Microsomal epoxide hydrolase is involved in the cerebral epoxyeicosatrienoic acid metabolism
metabolism
-
the enzyme plays a role in the endocannabinoid signaling and a new arachidonic acid biosynthetic pathway
metabolism
role of microsomal epoxide hydrolase, Na+-taurocholate cotransporting polypeptide, and organic anion transporting polypeptide in hepatic sodium-dependent bile acid transport
metabolism
-
epoxide hydrolases comprise a family of enzymes important in detoxification and conversion of lipid signaling molecules, namely epoxyeicosatrienoic acids. Microsomal epoxide hydrolase is involved in the cerebral epoxyeicosatrienoic acid metabolism
-
physiological function
-
microsomal epoxide hydrolase and cytochrome P-450 ensure the rapid detoxification of epoxides generated during the oxidative metabolism of xenobiotics
physiological function
enzyme EPHX1 appears to play an important role in organ-specific human physiology . The enzyme is able to either detoxify or bioactivate a wide range of substrates. An EPHX1 transcription-independent (both cis and trans) regulatory role is suggested for E1-b', a distinct EPHX1 transcript generated from the upstream promoter expressed in a tissue-selective manner in ovaries. Complex EPHX1 gene regulation, overview. EPHX1 more readily converts xenobiotics than endogenous substrates and has mostly a detoxifying function. Microsomal EPHX1 plays a dual role in the biotransformation of xenobiotics. While it detoxifies certain carcinogenic compounds, e.g., butadiene, benzene, styrene etc., it can also activate procarcinogens such as polycyclic aromatic hydrocarbons on the other hand. EPHX1 is also expressed on the sinusoidal plasma membrane where it mediates the sodium-dependent transport of bile acids into hepatocytes. Role of EPHX1 in pathogenesis of neurodegeneration with differential expression in patients with Alzheimer's disease. EPHX1 plays a role in the styrene detoxification pathway with genetic susceptibility to DNA damage in exposed subjects
physiological function
EPHX1 is an endogenous modulator of drug dependence in mice. EPHX1 contributes to the cerebral metabolism of epoxyeicosatrienoic acids which might interfere with neuronal signal transmission, vasodilation, cardiovascular homeostasis, and inflammation. Role of mEH in bioactivation of certain polycyclic aromatic hydrocarbons, e.g. 7,12-dimethylbenz[a]anthracene
physiological function
-
epoxide hydrolases are the key enzymes in the biosynthesis of polyether ladder compounds such as the brevetoxins which are produced by the dinoflagellate Karenia brevis, which is the principal HAB organism in the Gulf of Mexico also known as the Florida red tide dinoflagellate. Microsomal epoxide hydrolases, mEHs, are involved in the metabolism of xenobiotics
physiological function
in human liver fractions and hepatocytes, oxetane hydrolysis by mEH is the only oxetane ring-opening metabolic route, with no contribution from soluble epoxide hydrolase (sEH, EC 3.3.2.10) or from cytochrome P450-catalyzed oxidation
physiological function
microsomal epoxide hydrolase (mEH) is a bifunctional protein that plays a central role in the metabolism of numerous xenobiotics as well as mediating the sodium-dependent transport of bile acids into hepatocytes. These compounds are involved in cholesterol homeostasis, lipid digestion, excretion of xenobiotics and the regulation of several nuclear receptors and signaling transduction pathways. The type I form of microsomal epoxide hydrolase (mEH) is expressed on the hepatocyte endoplasmic reticulum membrane plays a central role in the metabolism of numerous xenobiotics. The type II form is targeted to the plasma membrane where it can mediate the sodium-dependent transport of bile acids in parallel with the sodium-taurocholate cotransporting protein (Ntcp)
physiological function
microsomal epoxide hydrolase (mEH) plays a significant role in the hepatic transport of conjugated bile acids
physiological function
Microsomal epoxide hydrolase is a xenobiotic-metabolizing enzyme, which hydrolyzes potentially genotoxic epoxides to less reactive dihydrodiols. Key features of mEH comprise a broad substrate spectrum and almost ubiquitous expression in all body tissues, with particularly high expression in liver and kidney,consistent with a central role in detoxification. Enzyme mEH is also capable of metabolizing endogenous compounds including epoxy steroids and arachidonic acid-derived lipid signaling molecules, so-called epoxyeicosatrienoic acids (EETs). Genetic enhancement of microsomal epoxide hydrolase through mutation E404D improves metabolic detoxification but impairs cerebral blood flow regulation. mEH E404D animals also show faster metabolization of a specific class of endogenous eicosanoids, arachidonic acid-derived epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs). Significantly higher DHETs/EETs ratios are found in mEH E404D liver, urine, plasma, brain and cerebral endothelial cells compared to WT controls, suggesting a broad impact of the mEH mutant on endogenous EETs metabolism
physiological function
soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) in the metabolic pathway of arachidonic acid
physiological function
the microsomal epoxide hydrolase plays a role in detoxification of 4-vinylcyclohexene diepoxide and is regulated by phosphatidylinositol-3 kinase signaling (PI3K). 4-Vinylcyclohexene diepoxide (VCD) is a metabolite of 4-vinylcyclohexene (VCH) which has the potential to be formed in the ovary through CYP2E1 activity. Functional role for mEH in the rat ovary involvement of PI3K signaling in regulation of ovarian xenobiotic metabolism by mEH
physiological function
the microsomal epoxide hydrolase plays a role in detoxification of 4-vinylcyclohexene diepoxide and is regulated by phosphatidylinositol-3 kinase signaling. 4-Vinylcyclohexene diepoxide (VCD) is a metabolite of 4-vinylcyclohexene (VCH) which has the potential to be formed in the ovary through CYP2E1 activity. The inactive tetrol metabolite (4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane) can be formed in mouse ovarian follicles, potentially through detoxification action of mEH. mEH can bioactivate the ovotoxic chemical 7,12-dimethylbenz[a]anthracene (DMBA) to the more toxic compound, DMBA-3,4-diol-1,2-epoxide
physiological function
-
the microsomal epoxide hydrolase plays a role in detoxification of 4-vinylcyclohexene diepoxide and is regulated by phosphatidylinositol-3 kinase signaling (PI3K). 4-Vinylcyclohexene diepoxide (VCD) is a metabolite of 4-vinylcyclohexene (VCH) which has the potential to be formed in the ovary through CYP2E1 activity. Functional role for mEH in the rat ovary involvement of PI3K signaling in regulation of ovarian xenobiotic metabolism by mEH
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additional information
evaluation of different epoxide hydrolase (EH) enzymes in the hydrolysis of skin-relevant fatty acid epoxides and comparison to the products to those of acid-catalyzed hydrolysis
additional information
homology structure modeling of human microsomal epoxide hydrolase using multiple templates, catalytic triad consits of Asp-His-Glu, and role of the oxyanion hole and the conserved motif (HGXP) in epoxide hydrolases, overview. Proposed mechanism for the ring-opening reaction catalyzed by mEH, analysis of substrate-enzyme interactions, docking and molecular dynamic simulation
additional information
-
homology structure modeling of human microsomal epoxide hydrolase using multiple templates, catalytic triad consits of Asp-His-Glu, and role of the oxyanion hole and the conserved motif (HGXP) in epoxide hydrolases, overview. Proposed mechanism for the ring-opening reaction catalyzed by mEH, analysis of substrate-enzyme interactions, docking and molecular dynamic simulation
additional information
mEH phenotyping of wild-type and naturally occuring mutants Y113H and H139R
additional information
-
mEH phenotyping of wild-type and naturally occuring mutants Y113H and H139R
additional information
quantitative structure-activity relationship (QSAR) modeling. The enzyme structure is used for predictions of small molecule binding
additional information
the N-terminal part anchors the EPHX1 protein into the membrane, while the C-terminus contains catalytic residues. The catalytic triad activity consists of fast nucleophilic attack of the substrate by the EPHX1-Asp226 residue forming an enzyme-substrate ester intermediate and subsequent hydrolysis of this complex by activated water. Water activation is fuelled by proton abstraction from the EPHX1-His431-Glu404 charge relay system. Tyr374 of human EPHX1 also performs a significant mechanistic role in substrate activation
additional information
-
the N-terminal part anchors the EPHX1 protein into the membrane, while the C-terminus contains catalytic residues. The catalytic triad activity consists of fast nucleophilic attack of the substrate by the EPHX1-Asp226 residue forming an enzyme-substrate ester intermediate and subsequent hydrolysis of this complex by activated water. Water activation is fuelled by proton abstraction from the EPHX1-His431-Glu404 charge relay system. Tyr374 of human EPHX1 also performs a significant mechanistic role in substrate activation
additional information
transition state of epoxide ring opening catalyzed by sEH, and binding mode of urea which mimic the transition state
additional information
-
two step mechanism of the alpha,beta-hydrolase fold type and endo-tet and exo-tet cyclization mechanisms
Show AA Sequence and Transmembrane Helices (3183 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
130000
49000
49500
50000
600000
-
enzyme aggregate formed in absence of amphiphathic detergents, gel filtration
800000
-
enzyme aggregate formed in absence of amphiphathic detergents, equilibrium sedimentation
additional information
49000
-
x * 49000, SDS-PAGE
additional information
-
enzyme aggregates in absence of amphipathic detergents
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
monomer
1 * 37700, calculated, 1 * 42000, SDS-PAGE of recombinant His-tagged protein
additional information
?
-
x * 49000, SDS-PAGE
additional information
structure comparison of homologous EPHX enzymes with domains of cytosolic and microsomal EPHX enzymes, overview. N-terminal and C-terminal catalytic domains and caps are highly conserved. The NC-loop has a variable length from 16 to 57 residues and the cap-loop has a variable length from five to 59 residues
additional information
structure comparison of homologous EPHX enzymes with domains of cytosolic and microsomal EPHX enzymes, overview. N-terminal and C-terminal catalytic domains and caps are highly conserved. The NC-loop has a variable length from 16 to 57 residues and the cap-loop has a variable length from five to 59 residues
additional information
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the enzyme possesses a long N-terminal transmembrane domain of 20 amino acids which acts as an anchor for cellular membranes
additional information
-
the enzyme possesses an N-terminal strong hydrophobic transmembrane anchor
additional information
the N-terminal part anchors the EPHX1 protein into the membrane, while the C-terminus contains catalytic residues
additional information
-
the N-terminal part anchors the EPHX1 protein into the membrane, while the C-terminus contains catalytic residues
additional information
-
the enzyme possesses a long N-terminal transmembrane domain of 20 amino acids which acts as an anchor for cellular membranes
additional information
structure comparison of homologous EPHX enzymes with domains of cytosolic and microsomal EPHX enzymes, overview. N-terminal and C-terminal catalytic domains and caps are highly conserved. The NC-loop has a variable length from 16 to 57 residues and the cap-loop has a variable length from five to 59 residues
additional information
-
structure analysis, amino acid sequence analysis and comparisons, the enzyme forms an alpha/beta hydrolase fold
additional information
-
the enzyme possesses a long N-terminal transmembrane domain of 20 amino acids which acts as an anchor for cellular membranes
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
molecular modelling of human enzyme by homology with the crystal structure of the Aspergillus niger enzyme at 1.8 A resolution, structure-activity relationships in epoxides inhibiting EH activity
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homology modeling. Structure exhibits a alpha/beta-hydrolase fold main domain with a lid domain over the active site
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A139G
-
a naturally occuring polymorphism, leads to reduced EPHX1 activity, but is not involved in pathogeneiss of asthma and COPD
E404D
-
mutation of the catalytic triad residue leads to increased activity compared to the wild-type enzyme
H139R
R43T
-
mutant shows reduced activity compared to the wild-type enzyme, molecular modelling
T113C
-
a naturally occuring polymorphism, leads to reduced EPHX1 activity, but is not involved in pathogeneiss of asthma and COPD
T275A
-
mutant shows similar activity compared to the wild-type enzyme, molecular modelling
Y113H
Y133H
-
naturally occuring mutation, frequencies in hepatocellular carcinoma, controls, and the chronic viral hepatitis subjects, respectively, overview
E404D
catalytic triad mutation, enzymatic activity of mEH can be greatly increased by a point mutation, leading to an E404D amino acid exchange in its catalytic triad, the mutation improves metabolic detoxification but impairs cerebral blood flow regulation. In liver microsomes from mutant mice, turnover of the xenobiotic compound phenanthrene-9,10-oxide is four times faster compared to wild-type liver microsomes. Hemodynamics are assessed in mEH E404D mutant and WT cerebral cortex and hippocampus using cerebral blood volume (CBV)-based functional magnetic resonance imaging (fMRI). Basal CBV0 levels are similar between mEH E404D and control mice in both brain areas. But vascular reactivity and vasodilation in response to the vasodilatory drug acetazolamide are reduced in mEH E404D forebrain compared to WT controls by factor 3 and 2.6, respectively. Role of mEH E404D in acetazolamide-induced vasodilation in cerebral cortex and hippocampus
additional information
H139R
-
mutant shows increased activity compared to the wild-type enzyme, molecular modelling
H139R
-
natural genotype, frequency of the polymorphism, the mutant enzyme shows 25% increased activity compared to the wild-type enzyme
H139R
-
natural genotype, frequency of the polymorphism, the mutant enzyme shows increased activity compared to the wild-type enzyme
H139R
-
the mutation is a genetic contributor to chronic obstructive pulmonary disease susceptibility
H139R
-
there is a significant association between early-onset lung cancer and the presence of EPHX1 exon 4 variant H139R
H139R
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the naturally occuring mutation is a risk factor for hepatocellular carcinoma with both control and chronic hepatitis-infected individuals, association of GSTT1 and GSTM1 null genotypes and mEPHX polymorphisms with hepatitis virus-related HCC risk in an Indian population. Frequencies in hepatocellular carcinoma, controls, and the chronic viral hepatitis subjects, respectively, overview
H139R
naturally occuring enzyme mutation, a polymorphism in exon 4, involved in development of esophageal squamous cell carcinoma
H139R
rs2234922, A416>G, naturally occuring mutation, used as marker to predict EPHX1 activity
Y113H
-
mutant shows similar activity compared to the wild-type enzyme, molecular modelling
Y113H
-
natural genotype, frequency of the polymorphism, the mutant enzyme shows 40% reduced activity compared to the wild-type enzyme
Y113H
-
natural genotype, frequency of the polymorphism, the mutant enzyme shows reduced activity compared to the wild-type enzyme
Y113H
-
the mutant is associated with 40-50% decrease in microsomal epoxide hydrolase activity
Y113H
-
the mutation is a genetic contributor to chronic obstructive pulmonary disease susceptibility
Y113H
-
the mutation is associated with higher risk of squamous cell esophageal cancer
Y113H
-
the mutation leads to altered enzyme activity, but is not associated with pancreatic diseases
Y113H
naturally occuring enzyme mutation, a polymorphism in exon 3, involved in development of esophageal squamous cell carcinoma (ESCC), exon 3 slow genotype predicts low mEH activity associated with the ESCC risk. Elevated ESCC risk estimates are seen in smokers independent of genotypes but the association is stronger among smokers with exon 3 variant
Y113H
rs1051740, T337>C, naturally occuring mutation, used as marker to predict EPHX1 activity
additional information
-
genotyping of 3553 humans, enzyme polymorphisms are not associated with colon cancer
additional information
-
genotyping of 497 humans, enzyme polymorphisms are associated with esophageal squamous-cell-carcinoma, ESCC, and smoking or areca chewing, higher enzyme activity can contribute to lower the risk of cancer development, overview
additional information
-
naturally occurring genetic polymorphisms of the enzyme are responsible for varying susceptibility of cigarette smoking humans to chronic obstructive pulmonary disease, COPD
additional information
-
genotyping and identifcation of single nucleotide polymorphisms c416A/G, rs2234922, and c337T/C, role of the mutations in carbamazepine treatement of epilepsy, overview
additional information
genotype analysis of the EPHX1 intron 1 polymorphism in the Lancaster County Old Order Amish population, identification of heterozygous mutations in human EPHX1 that result in a 95% decrease in mEH expression levels. EPHX1 transcription is significantly inhibited by two heterozygous mutations observed in the Old Order Amish population that present numerous hypercholanemic subjects in the absence of liver damage suggesting a defect in bile acid transport into the hepatocyte. The identity of the regulatory proteins binding to these sites, established using biotinylated oligonucleotides in conjunction with mass spectrometry is poly(ADP-ribose)polymerase-1 (PARP-1) (bound to the EPHX1 proximal promoter) and a linker histone complex, H1.2/Aly (bound to a regulatory intron 1 site). High frequency of the H1.2 site polymorphism in the Amish population results in a potential genetic predisposition to hypercholanemia
additional information
-
genotype analysis of the EPHX1 intron 1 polymorphism in the Lancaster County Old Order Amish population, identification of heterozygous mutations in human EPHX1 that result in a 95% decrease in mEH expression levels. EPHX1 transcription is significantly inhibited by two heterozygous mutations observed in the Old Order Amish population that present numerous hypercholanemic subjects in the absence of liver damage suggesting a defect in bile acid transport into the hepatocyte. The identity of the regulatory proteins binding to these sites, established using biotinylated oligonucleotides in conjunction with mass spectrometry is poly(ADP-ribose)polymerase-1 (PARP-1) (bound to the EPHX1 proximal promoter) and a linker histone complex, H1.2/Aly (bound to a regulatory intron 1 site). High frequency of the H1.2 site polymorphism in the Amish population results in a potential genetic predisposition to hypercholanemia
additional information
identification of two heterozygous mutations in gene EPHX1 intron-1, heterozygous polymorphism phenotype, overview. EPHX1 intron-1 heterozygous polymorphism are previously described in a high percentage of the Lancaster County Old Order Amish population that present numerous hypercholanemic subjects without liver injury, suggesting the loss of transport capacity. No mutations have been detected in the NTCP gene from this population
additional information
significant interaction is seen between mEH exon 3 and exon 4 genotypes and between predicted mEH activity and positive family history of cancer suggesting an association of ESCC risk with mEH polymorphisms which get modified by tobacco smoking and positive family history of cancer
additional information
-
significant interaction is seen between mEH exon 3 and exon 4 genotypes and between predicted mEH activity and positive family history of cancer suggesting an association of ESCC risk with mEH polymorphisms which get modified by tobacco smoking and positive family history of cancer
additional information
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mEH knockout mice are less sensitive to the carcinogenic activity of 7,12-dimethylbenz[a]anthracene compared to wild-type mice, but show no altered phenotype
additional information
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significant difference in extracellular dopamine uptake is observed between mEH-/- and wild-type mice
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
0°C, 50 mM sodium phosphate buffer, pH 7.0, 2 months, stable
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4C, stable for at least 3 months
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
multiple enzyme forms
partially 2.4fold from liver using PEG precipitation, and to homogeneity by ion exchange, hydrophobic interaction chromatography, and hydroxylapatite chromatography
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partially from liver
partially from liver by micosome preparation, two steps of gel filtration, separation from the cholesterol epoxide hydrolase, EC 3.3.2.11
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preparation of cytosolic fraction by ultracentrifugation
preparation of liver microsomes, separation from the cholesterol 5,6-oxide hydrolase, EC 3.3.2.11, by immunoprecipitation
recombinant His-tagged enzyme from Saccharomyces cerevisiae strain WA6 by nickel affinity chromatography
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recombinant His-tagged mEH isozymes from Escherichia coli by nickel affinity chromatography and dialysis
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to homogeneity from liver of phenobarbital- and isosafrole-treated rats, separation from the cholesterol 5,6-oxide hydrolase, EC 3.3.2.11, by immunoprecipitation
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preparation of liver microsomes, separation from the cholesterol 5,6-oxide hydrolase, EC 3.3.2.11, by immunoprecipitation
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preparation of liver microsomes, separation from the cholesterol 5,6-oxide hydrolase, EC 3.3.2.11, by immunoprecipitation
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
baculovirus expression system
expressed in a baculovirus expression system in High Five insect cell cultures (derived from Trichoplusia ni)
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expressed in Escherichia coli
expression in Escherichia coli
expression of His-tagged enzyme in Saccharomyces cerevisiae strain WA6, the N-terminal His-tag reduces enzyme activity by 75%, therefore a C-terminal His-tag is used
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gene EPHX1 is located on chromosome 1, DNA and amino acid sequence determination and analysis, expression of liver enzyme in Schizosaccharomyces pombe, expression in Cos-1 cells, expression using the baculovirus system
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gene EPHX1, located on chromosome 1 (1q42.12) consists of nine exons, and spans about 35 kb, exons 2-9 of EPHX1 encode three transcription variants differing in the 5'-untranslated region, while each translated protein product has 455 amino acids. Human EPHX1 expression in the liver is selectively driven by the proximal E1 promoter, but an alternative promoter region (E1-b promoter) drives expression in other tissues from both adult and fetal sources, e.g. an EPHX1 transcript (E1-b') generated from the upstream promoter is reported to be expressed in a tissue-selective manner with the highest level in human ovary. The E1-b promoter region harbors several functionally important polymorphisms including a double Alu insertion, which may influence interindividual susceptibility to toxicity of xenobiotics
gene EPHX1, sequencing of the EPHX1 5' region (-784/-1), 9 exons, intron 1, exon intron boundaries and the 3' untranslated region, analysis of EPHX1 transcriptional activity mediated by the proximal promoter region in HepG2 cells
genotyping of patients from the Copenhagen City Heart Study for EPHX1 polymorphisms
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screening of different Karenia brevis transcriptome libraries and enzyme cloning, recombinant expression of His-tagged mEH isozymes in Escherichia coli
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the E1-b promoter functions as the primary driver of EPHX1 expression in human tissues, E1 promoter directs expression only in the liver, analysis of promoters and regulation enzyme expression in tissues, expression in Hep-G2 cells and 293A cells, co-expression of GATA-4, overview
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
4-vinylcyclohexene diepoxide (VCD) increases mRNA and protein expression of microsomal epoxide hydrolase (mEH). mEH mRNA and enzyme activity expression are shown to increase in small pre-antral follicles of mouse ovaries following repeated daily dosing (15d) with VCD
CEBPA (116897) interacts with DNA-bound NFY (A subunit, 189903, B subunit, 189904, C subunit, 605344) as an additional regulator of EPHX1 expression. Nuclear receptors HNF4A (600281), CAR (NR1I3, 603881), and RXR (RXRA, 180245 and RXRB, 180246) also bind to the proximal EPHX1 promoter region and regulate its expression in human hepatocytes
enzyme mRNA and protein level do not change until 4 days after 4-vinylcyclohexene diepoxide exposure (0.03 mM)
exposure to 4-vinylcyclohexene results in increased mRNA and protein expression of microsomal epoxide hydrolase
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GATA4 (OMIM: 600576) is the major activator of EPHX1 expression. EPHX1 expression is induced by phenobarbital, beta-naphthoflavone, benzanthracene, and trans-stilbene oxide in human fetal hepatocytes in vitro
HNF3 (FOXA1, 602294 and FOXB1, 600288) acts as a co-repressor in HepG2 cells
increase of mEH expression after treatment with medroxy-progesterone 17-acetate in the estrogene receptor alpha-containing ECC1-PRAB72 cells, but not in estrogene receptor alpha-negative IKPRAB-36 cells
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inhibition of PI3K signaling increases mEH mRNA and protein expression. In a post-natal day 4 Fischer 344 rat whole ovary culture system, mEH mRNA is increased on day 4 of 4-vinylcyclohexene exposure, followed by increased mEH protein after 6 days
mEH expression is regulated by progesterone, but only in the presence of the progesterone receptors as well as estrogene receptor alpha, overview
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methyl-2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate is a potent inducer of transcription factor Nrf2 (nuclear factor, erythroid derived 2) and significantly alters the expression of EPHX1 protein in mice indicating a potential role of redox homeostasis in EPHX1 expression
relative to controls, meh mRNA is increased on day 4 of 4-vinylcyclohexene diepoxide exposure, followed by increased mEH protein after 6 days. Inhibition of phosphatidyinositol-3 kinase signaling increases mEH mRNA and protein expression
repeated administration of methamphetamine, METH, results in an increase in mEH-positive glia-like cells, mobilization of astroglial cells to synthesize mEH in response to METH
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the enzyme's protein level is significantly increased by phosphatidyinositol-3 kinase inhibition by 221% on day 4 and 14% on day 6 relative to control-treated ovaries
transcripts of Eha can be detected under the ligninolytic and nonligninolytic conditions as well as induced by anthracene
methyl-2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate is a potent inducer of transcription factor Nrf2 (nuclear factor, erythroid derived 2) and significantly alters the expression of EPHX1 protein in mice indicating a potential role of redox homeostasis in EPHX1 expression
methyl-2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate is a potent inducer of transcription factor Nrf2 (nuclear factor, erythroid derived 2) and significantly alters the expression of EPHX1 protein in mice indicating a potential role of redox homeostasis in EPHX1 expression
relative to controls, meh mRNA is increased on day 4 of 4-vinylcyclohexene diepoxide exposure, followed by increased mEH protein after 6 days. Inhibition of phosphatidyinositol-3 kinase signaling increases mEH mRNA and protein expression
relative to controls, meh mRNA is increased on day 4 of 4-vinylcyclohexene diepoxide exposure, followed by increased mEH protein after 6 days. Inhibition of phosphatidyinositol-3 kinase signaling increases mEH mRNA and protein expression
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
drug development
medicine
synthesis
analysis
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development of a fluorescence-based assay using substrate cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate and application as a useful tool for the discovery of structure-activity relationships among mEH inhibitors and for the screening chemical library with high accuracy and with a Z' value of approximately 0.7
analysis
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development of a fluorescence-based assay using substrate cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate and application as a useful tool for the discovery of structure-activity relationships among mEH inhibitors and for the screening chemical library with high accuracy and with a Z' value of approximately 0.7
drug development
the enzyme is an important therapeutic target for chronic diseases such as hypertension, diabetes and inflammation
medicine
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high EPHX1 activity is associated with an increased risk for lifetime asthma, which varies by glutathione S-transferase P1 Ile105Val genotype and by residential proximity to major roads. Among children with glutathione S-transferase P1 105Val/Val genotype, those who have high EPHX1 phenotype have a fourfold increased risk of lifetime asthma. Among children living within 75 metres of a major road, those with high EPHX1 activity had a 3.2-fold higher lifetime asthma risk. The results are similar for current, early persistent and late onset asthma
medicine
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incubation of ovaries in a neonatal mouse ovarian culture system in presence of 7,12-dimethylbenz[a]anthracene. At 1 mM 7,12-dimethylbenz[a]anthracene, follicle loss and increased microsomal epoxide hydrolase protein are measured by 6 h. mRNA encoding epoxide hydrolase markedly increases after 2 days of incubation, and this increase precedes accelerated follicle loss at 4 days
medicine
investigation on the expression and genetic polymorphism of microsomal epoxide hydrolase in non-small cell lung cancer patients. Enzyme is expressed in 83% of biopsies analyzed, and the major allelic expression pattern is fast type (Tyr113) in exon 3 (90.3%) and slow type (His139) in exon 4 (100%). A significant difference in patient survival is found when enzyme expression and adriamycin-containing chemotherapy are used to group patients. With respect to cancer risk and disease progression, the expression level of enzyme seems as important as genetic polymorphism
medicine
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investigation on the influence of single nucleotide polymorphisms in EPHX1 on well characterized chronic obstructive pulmonary disease and intermediate phenotypes. The EPHX1 exon 3 polymorphism is not associated with an increased risk of chronic obstructive pulmonary disease, nor is the EPHX1 exon 4 polymorphism. In addition, none of the EPHX1 haplotypes are associated with an increased risk of any chronic obstructive pulmonary disease phenotype
medicine
-
significant association of prostate cancer risk with exon 3 variant genotypes of microsomal epoxide hydrolase alone or in combination with tobacco users, whereas in exon 4 genotypes, no association is observed. T/C polymorphism of CYPA1 gene is an additional predisposing factor
medicine
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study on polymorphisms of microsomal epoxide hydrolase. Genotype frequencies of exon 3 are Tyr113Tyr 50.4%, Tyr113His 42.1%, His113His 7.5%, and on exon 4 His139His 69.2%, His139Arg 28.6%, Arg133Arg 2.2%
medicine
-
study on the effect of enzyme genotype on risk of myocardial infarction of smokers and non-smokers among patients with a first acute non-fatal myocardial infarction. EPHX1 genotype is not associated with risk of myocardial infarction, regardless of smoking status, and does not play a significant role in the development of coronary heart disease
medicine
-
EPHX1 does not play a role in the initiation of pancreatic inflammation or cancer
medicine
-
genetic mEPHX variants are positively associated with viral-related hepatocellular carcinoma risk
medicine
-
patients with exon 3 genotypes (Tyr113His, His113His) and 113His allele are at risk of squamous cell esophageal cancer, none of haplotype combinations of exon 3 (Y113H) and exon 4 (H139R) polymorphisms show modulation of risk for squamous cell esophageal cancer
medicine
-
polymorphisms in the microsomal epoxide hydrolase gene (EPHX1 His113-His113 genotype) are associated with chronic obstructive pulmonary disease
medicine
-
the exon 3 His genotype of the mEH gene polymorphism alone or in combination with tobacco-users are significantly associated with the risk of sporadic bladder cancer
medicine
-
there is no association of EPHX1 gene variation with susceptibility to chronic obstructive pulmonary disease or disease severity
medicine
-
there is no risk-modifying effect of genetic polymorphisms in microsomal epoxide hydrolase on head and neck carcinogenesis, except for the predicted high activity variant H139R in patients with hypopharyngeal carcinoma
synthesis
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the enantioselective enzyme is useful in production of chiral substances, e.g. production of (2R,3S)-ethyl 3-phenylglycidate with 95% enantiomeric excess and 26% yield in 12 h from 0.2% (w/v) of the racemat by whole cells of Pseudomonas sp. strain BZS21, maximal activity with dimethyl formamide as co-solvent
synthesis
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the purified recombinant enzyme can be used as biocatalyst for kinetic resolution of racemic styrene oxide with the result of over 99% enantiopure (S)-styrene oxide in 23,5% yield
synthesis
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enzyme prefers (R)-styrene oxide. Production of enantiopure (S)-styrene oxide by use of enzyme in batch kinetic resolution of racemic styrene oxide
synthesis
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highly enantioselective synthesis of chiral 1,2 diols from epoxides in ionic liquid [bmim][PF6] or [bmim][Tf2N] in presence of 10% water
synthesis
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the enantioselective enzyme is useful in production of chiral substances, e.g. production of (2R,3S)-ethyl 3-phenylglycidate with 95% enantiomeric excess and 26% yield in 12 h from 0.2% (w/v) of the racemat by whole cells of Pseudomonas sp. strain BZS21, maximal activity with dimethyl formamide as co-solvent
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Release 2023.1 (January 2023)
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