Any feedback?
Information on EC 3.3.2.9 - microsomal epoxide hydrolase and Organism(s) Rattus norvegicus and UniProt Accession P07687
for references in articles please use BRENDA:EC3.3.2.9Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
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).
Specify your search results
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 taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
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, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
mEH
-
-
additional information
-
the enzyme belongs to the family of C-X bond hydrolase enzymes
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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 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
-
PATHWAY SOURCE
PATHWAYS
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).
CAS REGISTRY NUMBER
COMMENTARY
9048-63-9
-
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
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
-
-
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
?
-
-
-
-
?
16,17-epoxyandrost-4-en-3-one + H2O
16,17-dihydroxyandrost-4-en-3-one
-
high activity
-
-
?
2,3-epoxypropyl-p-methoxyphenyl ether + H2O
3-(3-methoxyphenoxy)propane-1,2-diol
-
-
-
-
?
2-methyl styrene oxide + H2O
(2R)-2-phenylpropane-1,2-diol
-
-
highly enantioselective in ionic liquid [bmim][PF6]in presence of 10% water
-
?
4-methyl-2-oxo-2H-chromen-7-yl oxiran-2-ylmethyl carbonate + H2O
?
-
-
-
-
?
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
-
?
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 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-(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 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-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
-
?
cis-stilbene oxide + H2O
(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
-
?
cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate + H2O
?
-
synthetic fluorescent substrate
-
-
?
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
-
?
phenanthrene-9,10-oxide + H2O
?
-
-
-
-
?
styrene 7,8-oxide + H2O
styrene glycol
-
-
-
-
?
additional information
?
-
microsomal epoxide hydrolase (mEH) has wide a substrate specificity
-
-
?
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
-
-
?
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
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
-
-
-
?
cis-stilbene oxide + H2O
(+)-(1R,2R)-1,2-diphenylethane-1,2-diol
-
-
-
?
16,17-epoxyandrost-4-en-3-one + H2O
16,17-dihydroxyandrost-4-en-3-one
-
high activity
-
-
?
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
?
-
-
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
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
Lipid
-
above the critrical micelle concentration gives kinetic pattern that mimics competitive inhibition
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
trichloropropene oxide
-
inhibits hydration of estroxide, androstene oxide and styrene 7,8-oxide
additional information
-
5,6alpha-epoxy-5alpha-cholestan-3beta-ol causes down-regulation of the enzyme, no effect by cholestyramine and clofibrate
-
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
-
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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
cytochrome P450
-
activation of microsomal epoxide hydrolase by interaction with cytochromes P450
-
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
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
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
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.063
(9E)-octadec-9-enamide
Rattus norvegicus
-
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
0.0004
2-(nonylsulfanyl)propanamide
Rattus norvegicus
-
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
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.029
-
substrate 4-nitrophenyl 6-oxabicyclo[3.1.0]hexane-3-carboxylate, pH 9.0, 37°C
0.048
-
substrate 4-methyl-2-oxo-2H-chromen-7-yl oxiran-2-ylmethyl carbonate, pH 9.0, 37°C
0.068
-
substrate cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate, pH 9.0, 37°C
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
8.9
9.4
-
somewhat higher than, hydration of styrene oxide in glycine buffer
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
hypophysectomy induces the liver enzyme in females and males
additional information
-
-
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
-
in the rat basal lung epoxide hydrolase activity is much lower than liver
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
additional information
microsomal epoxide hydrolase (mEH) is expressed in multiple tissues, including the ovary
additional information
-
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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
-
-
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
-
slightly higher enzyme activity in smooth compared to rough microsomes
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). HYEP_RAT
455
0
52582
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
49000
-
x * 49000, SDS-PAGE
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
-
enzyme aggregates in absence of amphipathic detergents
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
?
-
x * 49000, SDS-PAGE
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
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
0°C, 50 mM sodium phosphate buffer, pH 7.0, 2 months, stable
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
preparation of liver microsomes, separation from the cholesterol 5,6-oxide hydrolase, EC 3.3.2.11, by immunoprecipitation
-
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
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in a baculovirus expression system in High Five insect cell cultures (derived from Trichoplusia ni)
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme mRNA and protein level do not change until 4 days after 4-vinylcyclohexene diepoxide exposure (0.03 mM)
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
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
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
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
synthesis
-
highly enantioselective synthesis of chiral 1,2 diols from epoxides in ionic liquid [bmim][PF6] or [bmim][Tf2N] in presence of 10% water
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wixtrom, R.N.; Hammock, B.D.
Membrane-bound and soluble-fraction epoxide hydrolases
Biochem. Pharmacol. Toxicol.
1
1-93
1985
Oryctolagus cuniculus, Homo sapiens, Macaca mulatta, Mus musculus, Rattus norvegicus
-
Seidegard, J.; DePierre, J.W.
Microsomal epoxide hydrolase. Properties, regulation and function
Biochim. Biophys. Acta
695
251-270
1983
Oryctolagus cuniculus, Rattus norvegicus
Lu, A.Y.H.; Miwa, G.T.
Molecular properties and biological functions of microsomal epoxide hydrase
Annu. Rev. Pharmacol. Toxicol.
20
513-531
1980
Homo sapiens, Rattus norvegicus
Oesch, F.
Epoxide hydratase
Prog. Drug Metab.
3
253-301
1979
Cavia porcellus, Oryctolagus cuniculus, Felis catus, Mus musculus, Pigeon, quail, Rattus norvegicus, Sus scrofa, toad, trout
-
Oesch, F.
Epoxide hydratase
Mises Point Biochim. Pharmacol.
1
127-148
1977
Cavia porcellus, Oryctolagus cuniculus, Homo sapiens, Macaca mulatta, Mus musculus, Rattus norvegicus
-
Oesch, F.
Purification and specificity of a human microsomal epoxide hydratase
Biochem. J.
139
77-88
1974
Cavia porcellus, Homo sapiens, Rattus norvegicus
Lu, A.Y.H.; Ryan, D.; Jerina, D.M.; Daly, J.W.; Levin, W.
Liver microsomal expoxide hydrase. Solubilization, purification, and characterization
J. Biol. Chem.
250
8283-8288
1975
Rattus norvegicus
Bentley, P.; Oesch, F.
Purification of rat liver epoxide hydratase to apparent homogeneity
FEBS Lett.
59
291-295
1975
Rattus norvegicus
Knowles, R.G.; Burchell, B.
A simple method for purification of epoxide hydratase from rat liver
Biochem. J.
163
381-383
1977
Rattus norvegicus
Bentley, P.; Oesch, F.
Properties and amino acid composition of pure epoxide hydratase
FEBS Lett.
59
296-299
1975
Rattus norvegicus
Lu, A.Y.H.; Levin, W.
Purification and assay of liver microsomal epoxide hydrase
Methods Enzymol.
52
193-200
1978
Rattus norvegicus
Bindel, U.; Sparrow, A.; Schmassmann, H.; Golan, M.; Bentley, P.; Oesch, F.
Endogenous role of epoxide-hydratase. Development of a steroid epoxide-hydratase assay and properties of the enzyme
Eur. J. Biochem.
97
275-281
1979
Rattus norvegicus
Lu, A.Y.H.; Thomas, P.E.; Ryan, D.; Jerina, D.M.; Levin, W.
Purification of human liver microsomal epoxide hydrase. Differences in the properties of the human and rat enzymes
J. Biol. Chem.
254
5878-5881
1979
Homo sapiens, Rattus norvegicus
Bornstein, W.A.; Levin, W.; Thomas, P.E.; Ryan, D.E.; Bresnick, E.
Comparison of nuclear and microsomal epoxide hydrase from rat liver
Arch. Biochem. Biophys.
197
436-446
1979
Rattus norvegicus
Guengerich, F.P.; Wang, P.; Mitchell, M.B.; Mason, P.S.
Rat and human liver microsomal epoxide hydratase. Purification and evidence for the existence of multiple forms
J. Biol. Chem.
254
12248-12254
1979
Homo sapiens, Rattus norvegicus
Ota, K.; Hammock, B.D.
Cytosolic and microsomal epoxide hydrolases: differential properties in mammalian liver
Science
207
1479-1481
1980
Cavia porcellus, Mus musculus, Rattus norvegicus
Guenthner, T.M.; Bentley, P.; Oesch, F.
Microsomal epoxide hydrolase
Methods Enzymol.
77
344-349
1981
Rattus norvegicus
Vogel-Bindel, U.; Bentley, P.; Oesch, F.
Endogenous role of microsomal epoxide hydrolase. Ontogenesis, induction inhibition, tissue distribution, immunological behaviour and purification of microsomal epoxide hydrolase with 16alpha,17alpha-epoxyandrostene-3-one as substrate
Eur. J. Biochem.
126
425-431
1982
Rattus norvegicus
Guengerich, F.P.
Epoxide hydratase: properties and metabolic roles
Rev. Biochem. Toxicol.
4
5-30
1982
Bos taurus, Cavia porcellus, Homo sapiens, Mus musculus, Rattus norvegicus
-
Bulleid, N.J.; Graham, A.B.; Craft, J.A.
Microsomal epoxide hydrolase of rat liver. Purification and characterization of enzyme fractions with different chromatographic characteristics
Biochem. J.
233
607-611
1986
Rattus norvegicus
Beaune, P.H.; Cresteil, T.; Flinois, J.P.; Leroux, J.P.
Hydrophobic chromatography: a one-step method for the purification of human liver microsomal epoxide hydrolase
J. Chromatogr.
426
169-176
1988
Homo sapiens, Rattus norvegicus
Lacourciere, G.M.; Vakharia, V.N.; Tan, C.P.; Morris, D.I.; Edwards, G.H.; Moos, M.; Armstrong, R.N.
Interaction of hepatic microsomal epoxide hydrolase derived from a recombinent baculovirus expression system with an azarene oxide and an aziridine substrate analogue
Biochemistry
32
2610-2616
1993
Rattus norvegicus
Taura, K.i.; Yamada, H.; Naito, E.; Ariyoshi, N.; Mori, M.a.; Oguri, K.
Activation of microsomal epoxide hydrolase by interaction with cytochromes P450: kinetic analysis of the association and substrate-specific activation of epoxide hydrolase function
Arch. Biochem. Biophys.
402
275-280
2002
Rattus norvegicus
Summerer, S.; Hanano, A.; Utsumi, S.; Arand, M.; Schuber, F.; Blee, E.
Stereochemical features of the hydrolysis of 9,10-epoxystearic acid catalysed by plant and mammalian epoxide hydrolases
Biochem. J.
366
471-480
2002
Apium graveolens, Glycine max, Musa x paradisiaca, Nicotiana tabacum, Oryza sativa, Rattus norvegicus, Solanum tuberosum, Triticum aestivum, Zea mays
DuTeaux, S.B.; Newman, J.W.; Morisseau, C.; Fairbairn, E.A.; Jelks, K.; Hammock, B.D.; Miller, M.G.
Epoxide hydrolases in the rat epididymis: possible roles in xenobiotic and endogenous fatty acid metabolism
Toxicol. Sci.
78
187-195
2004
Rattus norvegicus
Morisseau, C.; Hammock, B.D.
Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles
Annu. Rev. Pharmacol. Toxicol.
45
311-333
2005
Homo sapiens, Mus musculus, Rattus norvegicus
Levin, W.; Michaud, D.P.; Thomas, P.E.; Jerina, D.M.
Distinct rat hepatic microsomal epoxide hydrolases catalyze the hydration of cholesterol 5,6alpha-oxide and certain xenobiotic alkene and arene oxides
Arch. Biochem. Biophys.
220
485-494
1983
Rattus norvegicus
Astroem, A.; Eriksson, M.; Eriksson, L.C.; Birberg, W.; Pilotti, A.; DePierre, J.W.
Subcellular and organ distribution of cholesterol epoxide hydrolase in the rat
Biochim. Biophys. Acta
882
359-366
1986
Rattus norvegicus
Oesch, F.; Timms, C.W.; Walker, C.H.; Guenthner, T.M.; Sparrow, A.; Watabe, T.; Wolf, C.R.
Existence of multiple forms of microsomal epoxide hydrolases with radically different substrate specificities
Carcinogenesis
5
7-9
1984
Oryctolagus cuniculus, Rattus norvegicus
Lacourciere, G.M.; Armstrong, R.N.
Microsomal ans soluble epoxide hydrolases are members of the same family of C-X bond hydrolase enzymes
Chem. Res. Toxicol.
7
121-124
1994
Rattus norvegicus
Liu, M.; Sun, A.; Shin, E.J.; Liu, X.; Kim, S.G.; Runyons, C.R.; Markesbery, W.; KIm, H.C.; Bing, G.
Expression of microsomal epoxide hydrolase is elevated in Alzheimer's hippocampus and induced by exogenous beta-amyloid and trimethyl-tin
Eur. J. Neurosci.
23
2027-2034
2006
Homo sapiens, Rattus norvegicus
Sevanian, A.; McLeod, L.L.
Catalytic properties and inhibition of hepatic cholesterol-epoxide hydrolase
J. Biol. Chem.
261
54-59
1986
Rattus norvegicus
Newman, J.W.; Morisseau, C.; Hammock, B.D.
Epoxide hydrolases: their roles and interactions with lipid metabolism
Prog. Lipid Res.
44
1-51
2005
Homo sapiens, Mus musculus, Rattus norvegicus
Draper, A.J.; Hammock, B.D.
Inhibition of soluble and microsomal epoxide hydrolase by zinc and other metals
Toxicol. Sci.
52
26-32
1999
Homo sapiens, Mus musculus, Rattus norvegicus
Chiappe, C.; Leandri, E.; Hammock, B.D.; Morisseau, C.
Effect of ionic liquids on epoxide hydrolase-catalyzed synthesis of chiral 1,2-diols
Green Chem.
9
162-168
2007
Rattus norvegicus
Morisseau, C.; Newman, J.W.; Wheelock, C.E.; Hill Iii, T.; Morin, D.; Buckpitt, A.R.; Hammock, B.D.
Development of metabolically stable inhibitors of Mammalian microsomal epoxide hydrolase
Chem. Res. Toxicol.
21
951-957
2008
Rattus norvegicus
Rawal, S.; Morisseau, C.; Hammock, B.D.; Shivachar, A.C.
Differential subcellular distribution and colocalization of the microsomal and soluble epoxide hydrolases in cultured neonatal rat brain cortical astrocytes
J. Neurosci. Res.
87
218-227
2009
Rattus norvegicus
Pushparajah, D.S.; Umachandran, M.; Plant, K.E.; Plant, N.; Ioannides, C.
Differential response of human and rat epoxide hydrolase to polycyclic aromatic hydrocarbon exposure: studies using precision-cut tissue slices
Mutat. Res.
640
153-161
2008
Homo sapiens, Rattus norvegicus
Morisseau, C.; Bernay, M.; Escaich, A.; Sanborn, J.R.; Lango, J.; Hammock, B.D.
Development of fluorescent substrates for microsomal epoxide hydrolase and application to inhibition studies
Anal. Biochem.
414
154-162
2011
Homo sapiens, Rattus norvegicus
Abdull Razis, A.F.; Bagatta, M.; De Nicola, G.R.; Iori, R.; Ioannides, C.
Induction of epoxide hydrolase and glucuronosyl transferase by isothiocyanates and intact glucosinolates in precision-cut rat liver slices: importance of side-chain substituent and chirality
Arch. Toxicol.
85
919-927
2011
Rattus norvegicus
Bhattacharya, P.; Sen, N.; Hoyer, P.B.; Keating, A.F.
Ovarian expressed microsomal epoxide hydrolase: Role in detoxification of 4-vinylcyclohexene diepoxide and regulation by phosphatidylinositol-3 kinase signaling
Toxicol. Appl. Pharmacol.
258
118-123
2011
Mus musculus, Rattus norvegicus, Rattus norvegicus (P07687)
Bhattacharya, P.; Sen, N.; Hoyer, P.B.; Keating, A.F.
Ovarian expressed microsomal epoxide hydrolase role in detoxification of 4-vinylcyclohexene diepoxide and regulation by phosphatidylinositol-3 kinase signaling
Toxicol. Appl. Pharmacol.
258
118-23
2012
Rattus norvegicus (P07687), Mus musculus (Q9D379), Mus musculus, Rattus norvegicus Fischer 344 (P07687)
EXTERNAL LINKS (specific for EC-Number 3.3.2.9)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
