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Information on EC 1.6.5.2 - NAD(P)H dehydrogenase (quinone) and Organism(s) Rattus norvegicus and UniProt Accession P05982
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1.6.5.2 NAD(P)H dehydrogenase (quinone)IUBMB Comments
A flavoprotein. The enzyme catalyses a two-electron reduction and has a preference for short-chain acceptor quinones, such as ubiquinone, benzoquinone, juglone and duroquinone . The animal, but not the plant, form of the enzyme is inhibited by dicoumarol.
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Word Map
- 1.6.5.2
- s-transferase
- dismutase
- oxygenase-1
- catalase
- gst
-
chemopreventive
-
detoxify
-
two-electron
- dicoumarol
-
2-related
-
erythroid
-
cytoprotective
- hydroquinone
-
bioreductive
- mitomycin
- sulforaphane
- isothiocyanate
- cyp1a1
- nitroreductase
-
decolor
- hepa
-
one-electron
-
glutamate-cysteine
-
benzoapyrene
-
nrf2-mediated
- semiquinone
-
chemoprotective
-
nadph-cytochrome
-
nrf2-dependent
-
kelch-like
-
drug-metabolizing
-
nf-e2-related
-
anticarcinogenic
- medicine
- glucosinolates
- plastoquinone
- nadph-d
-
textile
-
ech-associated
- 3-methylcholanthrene
-
xenobiotic-metabolizing
-
nrf2-are
-
udp-glucuronosyltransferase
-
erythroid-derived
-
ethoxyresorufin
- beta-naphthoflavone
- tert-butylhydroquinone
-
ferredoxin-nadp+
-
peitc
- pharmacology
- drug development
- analysis
- degradation
- methemoglobinemia
-
pentoxyresorufin
- biotechnology
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
dt-diaphorase, diaphorase, quinone reductase, azoreductase, nad(p)h:quinone oxidoreductase 1, nad(p)h:quinone oxidoreductase, nad(p)h dehydrogenase, nad(p)h quinone oxidoreductase 1, ndh complex, nad(p)h quinone oxidoreductase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
azoreductase
-
-
-
-
dehydrogenase, reduced nicotinamide adenine dinucleotide (phosphate, quinone)
-
-
-
-
diaphorase
-
-
-
-
DT-diaphorase
DTD
-
-
-
-
flavoprotein NAD(P)H-quinone reductase
-
-
-
-
Menadione oxidoreductase
-
-
-
-
Menadione reductase
-
-
-
-
NAD(P)H dehydrogenase
-
-
-
-
NAD(P)H menadione reductase
-
-
-
-
NAD(P)H-quinone dehydrogenase
-
-
-
-
NAD(P)H-quinone oxidoreductase
-
-
-
-
NAD(P)H: (quinone-acceptor)oxidoreductase
-
-
-
-
NAD(P)H: menadione oxidoreductase
-
-
-
-
NADH-menadione reductase
-
-
-
-
Naphthoquinone reductase
-
-
-
-
NQO1
-
-
p-Benzoquinone reductase
-
-
-
-
Phylloquinone reductase
-
-
-
-
QR1
QR2
-
-
-
-
Quinone reductase
-
-
-
-
Reduced NAD(P)H dehydrogenase
-
-
-
-
reduced nicotinamide-adenine dinucleotide (phosphate) dehydrogenase
-
-
-
-
Viologen accepting pyridine nucleotide oxidoreductase
-
-
-
-
Vitamin K reductase
vitamin-K reductase
-
-
-
-
DT-diaphorase
-
-
-
-
QR1
-
-
-
-
Vitamin K reductase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -
SYSTEMATIC NAME
IUBMB Comments
NAD(P)H:quinone oxidoreductase
A flavoprotein. The enzyme catalyses a two-electron reduction and has a preference for short-chain acceptor quinones, such as ubiquinone, benzoquinone, juglone and duroquinone [6]. The animal, but not the plant, form of the enzyme is inhibited by dicoumarol.
CAS REGISTRY NUMBER
COMMENTARY
9032-20-6
-
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
1,8-dihydroxy-9,10-anthraquinone + NADPH
1,8-dihydroxy-9,10-anthraquinol + NADP+
-
-
-
-
?
1-hydroxy-2-[2-(nitrooxy)ethyl]-1-oxo-2-(2,4,6-trinitro-3-(nitro[2-(nitrooxy)ethyl]amino)phenyl)diazanium + NAD(P)H + H+
reduced 1-hydroxy-2-[2-(nitrooxy)ethyl]-1-oxo-2-(2,4,6-trinitro-3-(nitro[2-(nitrooxy)ethyl]amino)phenyl)diazanium + NAD(P)+
-
-
ratio kcat to Km value is 52000 per M and s
-
?
1-hydroxy-9,10-anthraquinone + NADPH
1-hydroxy-9,10-anthraquinol + NADP+
-
-
-
-
?
2,3-diglutathionyl-1,4-naphthoquinone + NADPH
2,3-diglutathionyl-1,4-naphthoquinol + NADP+
-
-
-
-
?
2,4,6-trinitrotoluene + NAD(P)H +
reduced 2,4,6-trinitrotoluene + NAD(P)+
-
-
ratio kcat to Km value is 670 per M and s
-
?
2,5-bis(ethylamine)-3,6-diaziridinyl-1,4-benzoquinone + NADPH
2,5-bis(ethylamine)-3,6-diaziridinyl-1,4-benzoquinol + NADP+
-
-
-
-
?
2,5-diaziridinyl-1,4-benzoquinone + NADPH
2,5-diaziridinyl-1,4-benzoquinol + NADP+
-
-
-
-
?
2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone + NADPH
2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinol + NADP+
-
-
-
-
?
2,5-dihydroxy-1,4-naphthoquinone + NADPH
2,5-dihydroxy-1,4-naphthoquinol + NADP+
-
-
-
-
?
2,5-dimethyl-1,4-benzoquinone + NADPH
2,5-dimethyl-1,4-benzoquinol + NADP+
-
-
-
-
?
2,5-dimethyl-1,4-naphthoquinone + NADPH
2,5-dimethyl-1,4-naphthoquinol + NADP+
-
-
-
-
?
2,5-dimethyl-3,6-diaziridinyl-1,4-benzoquinone + NADPH
2,5-dimethyl-3,6-diaziridinyl-1,4-benzoquinol + NADP+
-
-
-
-
?
2,6-dimethyl-1,4-benzoquinone + NADPH
2,6-dimethyl-1,4-benzoquinol + NADP+
-
-
-
-
?
2-hydroxy-1,4-naphthoquinone + NADPH
2-hydroxy-1,4-naphthoquinol + NADP+
-
-
-
-
?
2-methyl-1,4-benzoquinone + NADPH
2-methyl-1,4-benzoquinol + NADP+
-
-
-
-
?
2-methyl-1,4-naphthoquinone + NADH
2-methyl-1,4-naphthoquinol + NAD+
-
-
-
-
?
2-methyl-1,4-naphthoquinone + NADPH
2-methyl-1,4-naphthoquinol + NADp+
-
-
-
-
?
2-methyl-3-glutathionyl-5-hydroxy-1,4-naphthoquinone + NADPH
2-methyl-3-glutathionyl-5-hydroxy-1,4-naphthoquinol + NADP+
-
-
-
-
?
2-methyl-3-hydroxy-1,4-naphthoquinone + NADPH
2-methyl-3-hydroxy-1,4-naphthoquinol + NADP+
-
-
-
-
?
2-methyl-3-phytyl-1,4-naphthoquinone + NAD(P)H
2-methyl-3-phytyl-1,4-naphthohydroquinone + NAD(P)+
2-methyl-5-aziridinyl-1,4-benzoquinone + NADPH
2-methyl-5-aziridinyl-1,4-benzoquinol + NADP+
-
-
-
-
?
2-methyl-5-hydroxy-1,4-naphthoquinone + NADPH
2-methyl-5-hydroxy-1,4-naphthoquinol + NADP+
-
-
-
-
?
2-[nitro(2,4,6-trinitrophenyl)amino]ethyl nitrate + NAD(P)H +
reduced 2-[nitro(2,4,6-trinitrophenyl)amino]ethyl nitrate + NAD(P)+
-
-
ratio kcat to Km value is 570000 per M and s
-
?
4,5,6,7-tetranitro-1,3-dihydro-2H-benzimidazol-2-one + NAD(P)H +
reduced 4,5,6,7-tetranitro-1,3-dihydro-2H-benzimidazol-2-one + NAD(P)+
-
-
ratio kcat to Km value is 5000000 per M and s
-
?
4,5,6-trinitro-1,3-dihydro-2H-benzimidazol-2-one + NAD(P)H +
reduced 4,5,6-trinitro-1,3-dihydro-2H-benzimidazol-2-one + NAD(P)+
-
-
ratio kcat to Km value is 26000 per M and s
-
?
5,8-dihydroxy-1,4-naphthoquinone + NADPH
5,8-dihydroxy-1,4-naphthoquinol + NADP+
-
-
-
-
?
5-(1-aziridinyl)-3-(hydroxymethyl)-2-(3-hydroxy-1-propenyl)-1-methyl-1H-indole-4,7-dione + NAD(P)H
5-(1-aziridinyl)-3-(hydroxymethyl)-2-(3-hydroxy-1-propenyl)-1-methyl-1H-indole-4,7-diol + NAD(P)+
-
-
-
?
5-(aziridin-1-yl)-2,4-dinitrobenzamide + NAD(P)H
5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide + NAD(P)+
-
-
-
?
5-(aziridin-1-yl)-2,4-dinitrobenzamide + reduced dihydronicotineamide riboside
5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide + oxidized dihydronicotineamide riboside
-
-
-
?
5-hydroxy-1,4-naphthoquinone + NADPH
5-hydroxy-1,4-naphthosemiquinone + NADP+
-
-
-
-
?
9,10-phenanthrene quinone + NADPH
9,10-phenanthrene quinol + NADP+
-
-
-
-
?
alpha-tocopherolquinone + NAD(P)H
reduced alpha-tocopherolquinone + NAD(P)+
-
-
-
-
?
benzo[a]pyrene 3,6-quinone + NAD(P)H
benzo[a]pyrene 3,6-quinol
-
-
-
?
cyclized-dopamine o-quinone + NAD(P)H
cyclized-dopamine o-hydroquinone + NADP+
-
-
-
?
ethyl 5-aziridin-1-yl-2,4-dinitrobenzoate + NAD(P)H +
reduced ethyl 5-aziridin-1-yl-2,4-dinitrobenzoate + NAD(P)+
-
-
ratio kcat to Km value is 20000 per M and s
-
?
hydroxy(oxo)(3,6,8-trinitro-9H-carbazol-1-yl)ammonium + NAD(P)H +
reduced 2-[nitro(2,4,6-trinitrophenyl)amino]ethyl nitrate + NAD(P)+
-
-
ratio kcat to Km value is 500000 per M and s
-
?
menadione + reduced nicotinamide 2-azidoadenine dinucleotide
reduced menadione + oxidized nicotinamide 2-azidoadenine dinucleotide
-
-
-
?
menadione + reduced nicotinamide 8-azidoadenine dinucleotide
reduced menadione + oxidized nicotinamide 8-azidoadenine dinucleotide
-
-
-
?
N-methyl-N,2,4,6-tetranitroaniline + NAD(P)H +
reduced N-methyl-N,2,4,6-tetranitroaniline + NAD(P)+
-
-
ratio kcat to Km value is 260000 per M and s
-
?
N-methyl-N,2,4-trinitroaniline + NAD(P)H +
reduced N-methyl-N,2,4-trinitroaniline + NAD(P)+
-
-
ratio kcat to Km value is 52000 per M and s
-
?
NAD(P)H + H+ + oxidized 2,6-dichlorophenolindophenol
NAD(P)+ + reduced 2,6-dichlorophenolindophenol
NADH + H+ + 2-methyl-1,4-naphthoquinone
NAD+ + 2-methyl-1,4-naphthoquinol
-
-
-
-
?
NADPH + H+ + 2-methyl-1,4-naphthoquinone
NADP+ + 2-methyl-1,4-naphthoquinol
-
-
-
-
?
NADPH + H+ + oxidized 2,6-dichlorophenolindophenol
NADP+ + reduced 2,6-dichlorophenolindophenol
-
-
-
-
?
NADPH + H+ + quinone
NADP+ + ?
-
TNF alpha and LPS induce Nqo1 mRNA expression
-
-
?
nitracrine + NAD(P)H +
reduced nitracrine + NAD(P)+
-
-
i.e. N,N-dimethyl-N'-(1-nitro-9,10-dihydroacridin-9-yl)propane-1,3-diamine, ratio kcat to Km value is 1800 per M and s
-
?
oxidized 2,6-dichlorophenolindophenol + NADH + H+
reduced 2,6-dichlorophenolindophenol + NAD+
-
-
-
-
r
quinone + NAD(P)H
hydroquinone + NAD(P)+
-
protection of cells against damage by reactive oxygen species generated during oxidative cycling of quinones and semiquinone radicals
-
?
tetramethyl-1,4-benzoquinone + NADPH
tetramethyl-1,4-benzoquinol + NADP+
-
-
-
-
?
2-methyl-1,4-naphthoquinone + NAD(P)H
2-methyl-1,4-naphthoquinol + NAD(P)+
-
-
-
?
2-methyl-1,4-naphthoquinone + NAD(P)H
2-methyl-1,4-naphthoquinol + NAD(P)+
-
microsomal enzyme
-
?
2-methyl-1,4-naphthoquinone + NAD(P)H
2-methyl-1,4-naphthoquinol + NAD(P)+
-
artificial acceptor, trivial name menadione
-
?
2-methyl-1,4-naphthoquinone + NAD(P)H
2-methyl-1,4-naphthoquinol + NAD(P)+
-
artificial acceptor, trivial name menadione
-
?
2-methyl-1,4-naphthoquinone + NAD(P)H
2-methyl-1,4-naphthoquinol + NAD(P)+
-
artificial acceptor, trivial name menadione
-
?
2-methyl-1,4-naphthoquinone + NAD(P)H
2-methyl-1,4-naphthoquinol + NAD(P)+
-
artificial acceptor, trivial name menadione
-
?
2-methyl-3-phytyl-1,4-naphthoquinone + NAD(P)H
2-methyl-3-phytyl-1,4-naphthohydroquinone + NAD(P)+
-
trivial name vitamin K1
-
?
2-methyl-3-phytyl-1,4-naphthoquinone + NAD(P)H
2-methyl-3-phytyl-1,4-naphthohydroquinone + NAD(P)+
-
trivial name vitamin K1
-
?
NAD(P)H + H+ + oxidized 2,6-dichlorophenolindophenol
NAD(P)+ + reduced 2,6-dichlorophenolindophenol
-
-
-
?
NAD(P)H + H+ + oxidized 2,6-dichlorophenolindophenol
NAD(P)+ + reduced 2,6-dichlorophenolindophenol
-
-
-
?
NAD(P)H + H+ + oxidized 2,6-dichlorophenolindophenol
NAD(P)+ + reduced 2,6-dichlorophenolindophenol
-
-
-
?
NAD(P)H + H+ + oxidized 2,6-dichlorophenolindophenol
NAD(P)+ + reduced 2,6-dichlorophenolindophenol
-
-
-
-
?
NAD(P)H + H+ + oxidized 2,6-dichlorophenolindophenol
NAD(P)+ + reduced 2,6-dichlorophenolindophenol
-
microsomal enzyme
-
?
additional information
?
-
-
plays one of the main roles in the bioactivation of quinoidal drugs
-
-
?
additional information
?
-
-
the enzyme is involved in the metabolic activation of carcinogenic aristolochic acid
-
-
?
additional information
?
-
-
the main cytotoxicity mechanism of antitumour aziridinyl-benzoquinones is their two-electron reduction to alkylating products by NAD(P)H:quinone oxidoreductase. In addition to the activation of NQO1 the oxidative stress, presumably initiated by single-electron enzymatic reduction, plays an important role in the cytotoxicity of aziridinyl-substituted quinones
-
-
?
additional information
?
-
-
naphthoquinone-based vitamin (vitamin K1) is not a substrate for purified rat NQO1
-
-
?
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
NADH + H+ + 2-methyl-1,4-naphthoquinone
NAD+ + 2-methyl-1,4-naphthoquinol
-
-
-
-
?
NADPH + H+ + 2-methyl-1,4-naphthoquinone
NADP+ + 2-methyl-1,4-naphthoquinol
-
-
-
-
?
quinone + NAD(P)H
hydroquinone + NAD(P)+
-
protection of cells against damage by reactive oxygen species generated during oxidative cycling of quinones and semiquinone radicals
-
?
additional information
?
-
-
plays one of the main roles in the bioactivation of quinoidal drugs
-
-
?
additional information
?
-
-
the enzyme is involved in the metabolic activation of carcinogenic aristolochic acid
-
-
?
additional information
?
-
-
the main cytotoxicity mechanism of antitumour aziridinyl-benzoquinones is their two-electron reduction to alkylating products by NAD(P)H:quinone oxidoreductase. In addition to the activation of NQO1 the oxidative stress, presumably initiated by single-electron enzymatic reduction, plays an important role in the cytotoxicity of aziridinyl-substituted quinones
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-hydroxy-2-[2-(nitrooxy)ethyl]-1-oxo-2-(2,4,6-trinitro-3-(nitro[2-(nitrooxy)ethyl]amino)phenyl)diazanium
-
competitive
5,5'-dithiobis(2-nitrobenzoic acid)
-
1 mM, 67% inhibition, 10 mM, complete inhibition
5-hydroxy-7-bromoacetylflavone
-
0.00018 mM, 50% inhibition, irreversible, useful as affinity label
7-bromoacetylflavone
-
time-dependent inactivation within 30 s, 0.00074 mM, 50% inhibition
3,3'-methylene-bis(4-hydroxycoumarin)
-
competitive vs. NADH, uncompetitive vs. vitamin K1
dicoumarol
-
in the presence of 0.050 mM of dicoumarol, the protective effect of bromocriptine against H2O2 is completely abolished
dicoumarol
-
lack of effect of inhibition of DT-diaphorase by dicoumarol, when the cells are incubated with dopamine and reserpine. Significant cell death only when RCSN-3 cells are incubated with reserpine and dopamine together with the DT-diaphorase inhibitor dicoumarol
additional information
-
microsomal enzyme: not inhibited by dicoumarol, lapachol and p-chloromercuribenzoate
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3-nitrobenzanthrone
-
increases protein level and enzymatic activity of NQO1. Up to a 2.5fold increase in NQO1 activity with menadione as substrate in tissues of rats treated with 3-nitrobenzanthrone
alpha-methylbenzyl isothiocyanate
-
in vivo, the organ most susceptible to the inductive activity of the isothiocyanates is the urinary bladder, with alpha-methylbenzyl isothiocyanate and cyclohexylmethyl isothiocyanate being the most effective. Inductive activity in the bladder in vivo does not correlate with that in bladder cells in vitro
bromocriptine
-
significantly upregulates expression and activity (911% of untreated control) of NQO1, attenuates increase in protein-bound quinone in H2O2-treated PC12 cells, and protects PC12 cells against oxidative damage. Bromocriptine increases the expression and nuclear translocation of a basic leucine zipper transcription factor Nrf2, involved in the regulation of the enzyme
cyclohexylmethyl isothiocyanate
-
in vivo, the organ most susceptible to the inductive activity of the isothiocyanates is the urinary bladder, with alpha-methylbenzyl isothiocyanate and cyclohexylmethyl isothiocyanate being the most effective. Inductive activity in the bladder in vivo does not correlate with that in bladder cells in vitro
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.027
5-(1-aziridinyl)-3-(hydroxymethyl)-2-(3-hydroxy-1-propenyl)-1-methyl-1H-indole-4,7-dione
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2000
2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone
-
pH 7.0, 25Ā°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00005
1,amino-4-[(4-amino-3-sulfophenyl)amino]-anthraquinone-2-sulfonic acid
-
-
0.000077
1-amino-4-[(3-carboxyphenyl)amino]-anthraquinone-2-sulfonic acid
-
-
0.095
1-hydroxy-2-[2-(nitrooxy)ethyl]-1-oxo-2-(2,4,6-trinitro-3-(nitro[2-(nitrooxy)ethyl]amino)phenyl)diazanium
-
pH 7.0, 25Ā°C
0.0031
hydroxy(oxo)(3,6,8-trinitro-9H-carbazol-1-yl)ammonium
-
pH 7.0, 25Ā°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00024
0.039
-
activity in liver microsomes, reduction of menadione, cofactor NADPH
0.09
-
in kidney of control rats and in lung of rats treated with 40 mg/kg of 3-nitrobenzanthrone
0.121
-
activity in liver cytosol, reduction of 2,6-dichlorophenolindophenol, cofactor NADPH
0.128
-
activity in liver cytosol, reduction of 2,6-dichlorophenolindophenol, cofactor NADH
0.15
-
in kidney of rats treated with 0.4 or 4 mg/kg of 3-nitrobenzanthrone
0.153
-
activity in liver microsomes, reduction of menadione, cofactor NADH
0.157
-
activity in liver microsomes, reduction of 2,6-dichlorophenolindophenol, cofactor NADPH
0.63
-
activity in liver microsomes, reduction of 2,6-dichlorophenolindophenol, cofactor NADH
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
-
-
14080, 394352, 394354, 394356, 394357, 394362, 394363, 394366, 394371, 394382, 657644, 657654, 658402, 671034, 690145, 695280, 724747
-
in the Sprague Dawley strain, gender dimorphic expression of Nqo1 with female mRNA, protein, and activity levels being significantly higher than in males. Minimal differences in Nqo1 mRNA, protein, and activity levels between August Copenhagen x Irish males and females
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
in addition to protection of b-cells from toxic concentrations of the redox cycling quinone menadione, NQO1 also regulates the basal level of reduced-to-oxidized nucleotides
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). NQO1_RAT
274
0
30947
Swiss-Prot
Mitochondrion (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
32000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop method, crystals from a solution of 10 mg/ml enzyme, 1.45 M ammonium sulfate, 0.5% polyethylene glycol 8000, 30 mM Cibacron blue and 150 mM imidazole, pH 7.0, complex with NADP+ or duroquinone, 2.1 A resolution, structure and substrate binding mechanism
-
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
sucrose, 0.25 M, essential for stabilization during storage at -20Ā°C and purification
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
basal expression of NQO1 and NADPH cytochrome P450 oxidoreductase is comparable in isolated islets and liver
NQO1, but not NADPH cytochrome P450 oxidoreductase , is strongly induced in pancreatic beta-cells exposed to menadione
Sudan I induces NQO1 expression in rat liver, kidney, and lung, real-time polymerase chain reaction expression analysis
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
medicine
drug development
-
cytoprotective effect of bromocriptine involving PI3K- and Nrf2-mediated upregulation of the antioxidant enzyme NQO1, which may be a therapeutic strategy to protect cells from oxidative damage in ParkinsonĀs disease
drug development
-
induction of phase 2 enzymes, e.g. NQO1 increases resistance to chemical carcinogenesis. Isothiocyanates can therefore be valuable chemopreventative agents, and the specificity of these substances toward the urinary bladder suggest that they may be particularly useful for protecting against bladder cancer
medicine
-
3-nitrobenzanthrone is capable to induce NQO1 and CYP1A1 in lungs and kidney of rats thereby enhancing its own genotoxic and carcinogenic potential
medicine
-
acute manganese intoxication, similarly to that of cadmium and other heavy metals, increases both the hepatic level of Nrf2 and its transfer from the cytoplasm to the nucleus where it actively regulates the induction of phase II enzymes, e.g. NQO1
medicine
-
main function of QR1 is probably the detoxification of dietary quinones but it may also contribute to the reduction of vitamin K for its involvement in blood coagluation
medicine
-
neuroprotective role of DT-diaphorase against aminochrome neurotoxicity
medicine
-
strain difference where Sprague Dawley rats possess a sex-dependent expression and activity of Nqo1 and August Copenhagen x Irish rats exhibit no sexual dimorphism may provide an important tool when using these rat models for oxidative stress and cancer studies
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Skelly, J.V.; Suter, D.A.; Knox, R.J.; Garman, E.; Stuart, D.I.; Sanderson, M.R.; Roberts, J.J.; Neidle, S.
Preliminary crystallographic data for NAD(P)H quinone reductase isolated from the Walker 256 rat carcinoma cell line
J. Mol. Biol.
205
623-624
1989
Rattus norvegicus
Sharkis, D.H.; Swenson, R.P.
Purification by cibacron blue F3GA dye affinity chromatography and comparison of NAD(P)H:quinone reductase (E.C.1.6.99.2) from rat liver cytosol and microsomes
Biochem. Biophys. Res. Commun.
161
434-441
1989
Rattus norvegicus
Märki, F.; Martius, C.
Vitamin K-Reduktase, Darstellung und eigenschaften
Biochem. Z.
333
111-135
1960
Bos taurus, Gallus gallus, Oryctolagus cuniculus, Rattus norvegicus, Sus scrofa, Tinca vulgaris, Xenopus laevis
-
Rase, B.; Bartfai, T.; Ernster, L.
Purification of DT-diaphorase by affinity chromatography. Occurrence of two subunits and nonlinear Dixon and Scatchard plots of the inhibition by anticoagulants
Arch. Biochem. Biophys.
172
380-386
1976
Rattus norvegicus
Prestera, T.; Prochaska, H.J.; Talalay, P.
Inhibition of NAD(P)H:(quinone-acceptor) oxidoreductase by cibacron blue and related anthraquinone dyes: a structure-activity study
Biochemistry
31
824-833
1992
Rattus norvegicus
Segura-Aguilar, J.; Kaiser, R.; Lind, C.
Separation and characterization of isoforms of DT-diaphorase from rat liver cytosol
Biochim. Biophys. Acta
1120
33-42
1992
Rattus norvegicus
Deng, P.S.K.; Zhao, S.H.; Iyanagi, T.; Chen, S.
Photodependent inhibition of rat liver NAD(P)H:quinone acceptor oxidoreductase by (A)-2-azido-NAD+ and (A)-8-azido-NAD
Biochemistry
30
6942-6948
1991
Rattus norvegicus
Prochaska, H.J.
Purification and crystallization of rat liver NAD(P)H:(quinone-acceptor) oxidoreductase by cibacron blue affinity chromatography: identification of a new and potent inhibitor
Arch. Biochem. Biophys.
267
529-538
1988
Rattus norvegicus
Fasco, M.J.; Principe, L.M.
Vitamin K1 hydroquinone formation catalyzed by DT-diaphorase
Biochem. Biophys. Res. Commun.
104
187-192
1982
Rattus norvegicus
Lind, C.; Cadenas, E.; Hochstein, P.; Ernster, L.
DT-diaphorase: purification, properties, and function
Methods Enzymol.
186
287-301
1990
Bos taurus, Rattus norvegicus
Wallin, R.
Some molecular properties of NAD(P)H dehydrogenase from rat liver
Biochem. J.
181
127-135
1979
Rattus norvegicus
Chen, S.; Clarke, P.E.; Martino, P.A.; Deng, P.S.K.; Yeh, C.H.; Lee, T.D.; Prochaska, H.J.; Talalay, P.
Mouse liver NAD(P)H:quinone acceptor oxidoreductase: protein sequence analysis by tandem mass spectrometry, cDNA cloning, expression in Escherichia coli, and enzyme activity analysis
Protein Sci.
3
1296-1304
1994
Homo sapiens, Mus musculus, Rattus norvegicus
Li, R.; Bianchet, M.A.; Talalay, P.; Amzel, L.M.
The three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: mechanism of the two-electron reduction
Proc. Natl. Acad. Sci. USA
92
8846-8850
1995
Rattus norvegicus
Chen, S.; Knox, R.; Lewis, A.D.; Friedlos, F.; Workman, P.; Deng, P.S.K.; Fung, M.; Ebenstein, D.; Wu, K.; Tsai, T.M.
Catalytic properties of NAD(P)H:quinone acceptor oxidoreductase: study involving mouse, rat, human, and mouse-rat chimeric enzymes
Mol. Pharmacol.
47
934-939
1995
Homo sapiens, Mus musculus, Rattus norvegicus
Chen, S.; Deng, P.S.K.; Swiderek, K.; Li, M.; Chan, S.I.
Interaction of flavones and their bromoacetyl derivatives with NAD(P)H:quinone acceptor oxidoreductase
Mol. Pharmacol.
47
419-424
1995
Rattus norvegicus
Jaiswal, A.K.
Characterization and partial purification of microsomal NAD(P)H:quinone oxidoreductases
Arch. Biochem. Biophys.
375
62-68
2000
Rattus norvegicus
Anusevicius, Z.; Sarlauskas, J.; Cenas, N.
Two-electron reduction of quinones by rat liver NAD(P)H:quinone oxidoreductase: quantitative structure-activity relationships
Arch. Biochem. Biophys.
404
254-262
2002
Rattus norvegicus
Nemeikaite-Ceniene, A.; Sarlauskas, J.; Anusevicius, Z.; Nivinskas, H.; Cenas, N.
Cytotoxicity of RH1 and related aziridinylbenzoquinones: involvement of activation by NAD(P)H:quinone oxidoreductase (NQO1) and oxidative stress
Arch. Biochem. Biophys.
416
110-118
2003
Rattus norvegicus
Stiborova, M.; Frei, E.; Sopko, B.; Sopkova, K.; Markova, V.; Lankova, M.; Kumstyrova, T.; Wiessler, M.; Schmeiser, H.H.
Human cytosolic enzymes involved in the metabolic activation of carcinogenic aristolochic acid: evidence for reductive activation by human NAD(P)H:quinone oxidoreductase
Carcinogenesis
24
1695-1703
2003
Homo sapiens, Rattus norvegicus
Gustafson, D.L.; Siegel, D.; Rastatter, J.C.; Merz, A.L.; Parpal, J.C.; Kepa, J.K.; Ross, D.; Long, M.E.
Kinetics of NAD(P)H:quinone oxidoreductase I (NQO1) inhibition by mitomycin C in vitro and in vivo
J. Pharmacol. Exp. Ther.
305
1079-1086
2003
Homo sapiens, Mus musculus, Rattus norvegicus
Miseviciene, L.; Anusevicius, Z.; Sarlauskas, J.; Cenas, N.
Reduction of nitroaromatic compounds by NAD(P)H:quinone oxidoreductase (NQO1): the role of electron-accepting potency and structural parameters in the substrate specificity
Acta Biochim. Pol.
53
569-576
2006
Rattus norvegicus
Casalino, E.; Calzaretti, G.; Landriscina, M.; Sblano, C.; Fabiano, A.; Landriscina, C.
The Nrf2 transcription factor contributes to the induction of alpha-class GST isoenzymes in liver of acute cadmium or manganese intoxicated rats: comparison with the toxic effect on NAD(P)H:quinone reductase
Toxicology
237
24-34
2007
Rattus norvegicus
Fuentes, P.; Paris, I.; Nassif, M.; Caviedes, P.; Segura-Aguilar, J.
Inhibition of VMAT-2 and DT-diaphorase induce cell death in a substantia nigra-derived cell line--an experimental cell model for dopamine toxicity studies
Chem. Res. Toxicol.
20
776-783
2007
Rattus norvegicus
Diaz-Veliz, G.; Paris, I.; Mora, S.; Raisman-Vozari, R.; Segura-Aguilar, J.
Copper neurotoxicity in rat substantia nigra and striatum is dependent on DT-diaphorase inhibition
Chem. Res. Toxicol.
21
1180-1185
2008
Rattus norvegicus
Augustine, L.M.; Fisher, C.D.; Lickteig, A.J.; Aleksunes, L.M.; Slitt, A.L.; Cherrington, N.J.
Gender divergent expression of Nqo1 in Sprague Dawley and August Copenhagen x Irish rats
J. Biochem. Mol. Toxicol.
22
93-100
2008
Rattus norvegicus
Colucci, M.A.; Moody, C.J.; Couch, G.D.
Natural and synthetic quinones and their reduction by the quinone reductase enzyme NQO1: from synthetic organic chemistry to compounds with anticancer potential
Org. Biomol. Chem.
6
637-656
2008
Mus musculus, Rattus norvegicus, Homo sapiens (P15559), Homo sapiens
Munday, R.; Zhang, Y.; Munday, C.M.; Bapardekar, M.V.; Paonessa, J.D.
Structure-activity relationships and organ specificity in the induction of GST and NQO1 by alkyl-aryl isothiocyanates
Pharm. Res.
25
2164-2170
2008
Rattus norvegicus
Lim, J.H.; Kim, K.M.; Kim, S.W.; Hwang, O.; Choi, H.J.
Bromocriptine activates NQO1 via Nrf2-PI3K/Akt signaling: novel cytoprotective mechanism against oxidative damage
Pharmacol. Res.
57
325-331
2008
Rattus norvegicus
Stiborova, M.; Dracinska, H.; Mizerovska, J.; Frei, E.; Schmeiser, H.H.; Hudecek, J.; Hodek, P.; Phillips, D.H.; Arlt, V.M.
The environmental pollutant and carcinogen 3-nitrobenzanthrone induces cytochrome P450 1A1 and NAD(P)H:quinone oxidoreductase in rat lung and kidney, thereby enhancing its own genotoxicity
Toxicology
247
11-22
2008
Rattus norvegicus
Bianchet, M.A.; Erdemli, S.B.; Amzel, L.M.
Structure, function, and mechanism of cytosolic quinone reductases
Vitam. Horm.
78
63-84
2008
Homo sapiens, Mesocricetus auratus, Mus musculus, Rattus norvegicus
Nivinskas, H.; Nemeikaite-Ceniene, A.; Maroziene, A.; Normantiene, T.; Cenas, N.
Prooxidant cytotoxicity of chromate in mammalian cells: the opposite roles of DT-diaphorase and glutathione reductase
Z. Naturforsch. C
61
889-895
2007
Ovis aries, Rattus norvegicus
Bafana, A.; Chakrabarti, T.
Lateral gene transfer in phylogeny of azoreductase enzyme
Comput. Biol. Chem.
32
191-197
2008
Rattus norvegicus (P05982), Saccharomyces cerevisiae (Q07923), Mus musculus (Q64669), Cavia porcellus (Q8CHK7)
Stiborova”, M.; Dracinska”, H.; Martinek, V.; Svaskova”, D.; Hodek, P.; Milichovsky, J.; Hejdukova”, Z.; Brotanek, J.; Schmeiser, H.; Frei, E.
Induced expression of cytochrome P450 1A and NAD(P)H:quinone oxidoreductase determined at mRNA, protein, and enzyme activity levels in rats exposed to the carcinogenic azo dye 1-phenylazo-2-naphthol (Sudan I)
Chem. Res. Toxicol.
26
290-299
2013
Rattus norvegicus
Gray, J.P.; Karandrea, S.; Burgos, D.Z.; Jaiswal, A.A.; Heart, E.A.
NAD(P)H-dependent quinone oxidoreductase 1 (NQO1) and cytochrome P450 oxidoreductase (CYP450OR) differentially regulate menadione-mediated alterations in redox status, survival and metabolism in pancreatic beta-cells
Toxicol. Lett.
262
1-11
2016
Rattus norvegicus (P05982)
EXTERNAL LINKS (specific for EC-Number 1.6.5.2)
Transporter Classification Database (TCDB): 2.A.37.1.2, 2.A.37.1.1
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