Information on EC 1.14.14.1 - unspecific monooxygenase and Organism(s) Homo sapiens and UniProt Accession P10635

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Homo sapiens
UNIPROT: P10635
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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
1.14.14.1
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RECOMMENDED NAME
GeneOntology No.
unspecific monooxygenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
RH + [reduced NADPH-hemoprotein reductase] + O2 = ROH + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Deamination
-
-
-
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desulfation
-
-
-
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epoxidation
-
-
-
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hydroxylation
-
-
-
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N-dealkylation
-
-
-
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N-oxidation
-
-
-
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O-dealkylation
-
-
-
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oxidation
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redox reaction
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reduction
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reduction of azo, nitro, N-oxide groups
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-
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S-dealkylation
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-
-
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sulfoxidation
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-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
1,5-anhydrofructose degradation
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acetone degradation I (to methylglyoxal)
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acetone degradation III (to propane-1,2-diol)
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Amaryllidacea alkaloids biosynthesis
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Aminobenzoate degradation
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Arachidonic acid metabolism
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Biosynthesis of secondary metabolites
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bupropion degradation
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Caffeine metabolism
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Drug metabolism - cytochrome P450
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Fatty acid degradation
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Linoleic acid metabolism
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melatonin degradation I
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Metabolic pathways
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Metabolism of xenobiotics by cytochrome P450
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Microbial metabolism in diverse environments
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nicotine degradation IV
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nicotine degradation V
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Retinol metabolism
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Steroid hormone biosynthesis
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Tryptophan metabolism
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vanillin biosynthesis I
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arachidonic acid metabolism
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SYSTEMATIC NAME
IUBMB Comments
substrate,NADPH-hemoprotein reductase:oxygen oxidoreductase (RH-hydroxylating or -epoxidizing)
A group of P-450 heme-thiolate proteins, acting on a wide range of substrates including many xenobiotics, steroids, fatty acids, vitamins and prostaglandins; reactions catalysed include hydroxylation, epoxidation, N-oxidation, sulfooxidation, N-, S- and O-dealkylations, desulfation, deamination, and reduction of azo, nitro and N-oxide groups. Together with EC 1.6.2.4, NADPH---hemoprotein reductase, it forms a system in which two reducing equivalents are supplied by NADPH. Some of the reactions attributed to EC 1.14.15.3, alkane 1-monooxygenase, belong here.
CAS REGISTRY NUMBER
COMMENTARY hide
62213-32-5
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
cytochrome P450-dependent metabolism of omega-6 polyunsaturated fatty acids, overview
physiological function
additional information
-
loss of CYP3A4 activity may result in increased risk of drug toxicities and adverse drug reactions in patients with NADPH-P450 reductase mutations
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin + O2 + NADPH
?
show the reaction diagram
-
-
-
?
fenthion + O2 + NADPH
?
show the reaction diagram
fenthion-sulfoxide and fenthion-oxon, are formed by some CYPs although at very different levels, depending on the relative CYP hepatic content. Fenthion-oxon formation is favored and at low fenthion concentrations CYP2B6 and CYP1A2 are mainly involved in its formation. At higher levels, a more widespread CYP involvement is evident, as in the case of fenthion-sulfoxide
-
-
?
(S)-nicotine + O2 + NADPH
?
show the reaction diagram
-
substrate of CYP3A4, the reaction involves electron transfer via FMN
-
-
?
2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine + NADH + H+ + O2
?
show the reaction diagram
-
CYP1A2 catalyzes the first step of activation of the xenobiotic compound and its genotoxic effect, the second step is catalyzed by the sulfotransferase 1A1-1
-
-
?
2-amino-3-methylimidazo[4,5-f]quinoline + NADH + H+ + O2
?
show the reaction diagram
-
CYP1A2 catalyzes the first step of activation of the xenobiotic compound and its genotoxic effect, the second step is catalyzed by the N(O)-acetyltransferase.
-
-
?
3-cyano-7-ethoxycoumarin + O2 + NADPH
?
show the reaction diagram
4-(methylnitrosamino)-1-(3pyridyl)-1-butanone + O2 + reduced flavoprotein
?
show the reaction diagram
7-ethoxycoumarin + NADPH + O2 + FAD
7-hydroxycoumarin + NADP+ + FADH2 + ?
show the reaction diagram
-
wild-type enzyme and recombinant enzyme P4502B6 fused to yeast reductase and expressed in transgenic tobacco plants
-
-
?
7-ethoxyresorufin + O2 + NADPH
?
show the reaction diagram
7-methoxy-4-(trifluoromethyl)-coumarin + O2 + NADPH
?
show the reaction diagram
7-methoxyresorufin + O2 + NADPH
?
show the reaction diagram
-
-
-
-
?
adrenic acid + NADPH + H+ + O2
?
show the reaction diagram
-
i.e. all-cis-7,10,13,16-docosatetraenoic acid
-
-
?
aminopyrine + O2 + 2 H+
? + formaldehyde + H2O
show the reaction diagram
-
-
-
-
?
amiprofos-methyl + reduced flavoprotein + O2
? + oxidized flavoprotein + H2O
show the reaction diagram
-
-
-
-
?
arachidonic acid + NADPH + H+ + O2
?
show the reaction diagram
-
-
-
-
?
arachidonic acid + O2 + NADPH
20-hydroxyeicosatetraenoic acid + H2O + NADP+
show the reaction diagram
-
-
i.e. 20-HETE, a potent constrictor of renal microvessels and inhibits Na+ reabsorption in the proximal tubule and thick ascending limb, i.e.20-HETE
-
?
chlorotoluron + NADPH + O2 + FAD
?
show the reaction diagram
-
recombinant wild-type enzyme and enzyme mutant fused to yeast reductase expressed in transgenic potato plants
-
-
?
chlorotoluron + reduced flavoprotein + O2
? + oxidized flavoprotein + H2O
show the reaction diagram
-
-
-
-
?
chlorzoxazone + O2 + NADPH
?
show the reaction diagram
-
-
-
-
?
dibenzylfluorescein + O2 + NADPH
?
show the reaction diagram
dimethylaniline + O2 + NADPH
?
show the reaction diagram
-
substrate of CYP3A4
-
-
?
docosahexaenoic acid + NADPH + H+ + O2
22-hydroxydocosahexaenoic acid + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
eicosapentaenoic acid + NADPH + H+ + O2
20-hydroxyeicosapentaenoic acid + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
erythromycin + O2 + 2 H+
? + formaldehyde + H2O
show the reaction diagram
-
-
-
-
?
fenthion + O2 + NADPH
?
show the reaction diagram
fenthion-sulfoxide and fenthion-oxon, are formed by some CYPs although at very different levels, depending on the relative CYP hepatic content. Fenthion-oxon formation is favored and at low fenthion concentrations CYP2B6 and CYP1A2 are mainly involved in its formation. At higher levels, a more widespread CYP involvement is evident, as in the case of fenthion-sulfoxide
-
-
?
fenthion-sulfoxide + O2 + NADPH
fenthion-sulfone
show the reaction diagram
fluoxetine + O2 + 2 H+
? + formaldehyde + H2O
show the reaction diagram
-
-
-
-
?
linoleic acid + NADPH + H+ + O2
(9Z,12Z)-18-hydroxyoctadeca-9,12-dienoic acid + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
mefenacet + reduced flavoprotein + O2
? + oxidized flavoprotein + H2O
show the reaction diagram
-
-
-
-
?
N'-nitrosonornicotine + O2 + reduced flavoprotein
?
show the reaction diagram
norflurazon + reduced flavoprotein + O2
? + oxidized flavoprotein + H2O
show the reaction diagram
-
-
-
-
?
p-nitrophenol + O2 + NADPH
?
show the reaction diagram
CYP2E1
-
-
?
pendimethalin + reduced flavoprotein + O2
? + oxidized flavoprotein + H2O
show the reaction diagram
-
-
-
-
?
pyributicarb + reduced flavoprotein + O2
? + oxidized flavoprotein + H2O
show the reaction diagram
-
-
-
-
?
quinine + NADPH + H+ + O2
3-hydroxyquinine + NADP+ + H2O
show the reaction diagram
S-mephenytoin + O2 + 2 H+
?
show the reaction diagram
-
-
-
-
?
sertraline + O2 + 2 H+
demethylsertraline + formaldehyde + H2O
show the reaction diagram
-
i.e. (1S,4S)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine, a one-step oxidative N-demethylation
-
-
?
testosterone + O2 + NADPH
?
show the reaction diagram
CYP3A4
-
-
?
testosterone + O2 + NADPH + H+
6beta-hydroxytestosterone + NADP+ + H2O
show the reaction diagram
CYP3A4
-
-
?
tolbutamide + O2 + NADPH
?
show the reaction diagram
CYP2C9
-
-
?
trifluralin + reduced flavoprotein + O2
? + oxidized flavoprotein + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
4-(methylnitrosamino)-1-(3pyridyl)-1-butanone + O2 + reduced flavoprotein
?
show the reaction diagram
-
nicotine oxidase activity of CYP2A6, activates the tobacco-derived carcinogens to mutagenic products
-
-
?
7-ethoxycoumarin + NADPH + O2 + FAD
7-hydroxycoumarin + NADP+ + FADH2 + ?
show the reaction diagram
-
wild-type enzyme and recombinant enzyme P4502B6 fused to yeast reductase and expressed in transgenic tobacco plants
-
-
?
arachidonic acid + O2 + NADPH
20-hydroxyeicosatetraenoic acid + H2O + NADP+
show the reaction diagram
-
-
i.e. 20-HETE, a potent constrictor of renal microvessels and inhibits Na+ reabsorption in the proximal tubule and thick ascending limb
-
?
chlorotoluron + NADPH + O2 + FAD
?
show the reaction diagram
-
recombinant wild-type enzyme and enzyme mutant fused to yeast reductase expressed in transgenic potato plants
-
-
?
N'-nitrosonornicotine + O2 + reduced flavoprotein
?
show the reaction diagram
-
nicotine oxidase activity of CYP2A6, activates the tobacco-derived carcinogens to mutagenic products
-
-
?
quinine + NADPH + H+ + O2
3-hydroxyquinine + NADP+ + H2O
show the reaction diagram
-
in the microsomal membranes, CYP3A4 interacts with the NADPH-P450 reductase to receive electrons used in metabolism of drugs and xenobiotics. The heme unit in CYP3A4 is the catalytic center and electrons are transferred through reduced FMN to heme through electrostatic interactions
-
-
?
sertraline + O2 + 2 H+
demethylsertraline + formaldehyde + H2O
show the reaction diagram
-
i.e. (1S,4S)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine, a one-step oxidative N-demethylation
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cytochrome P450
-
-
-
flavoprotein
-
-
-
heme
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the heme unit in CYP3A4 is the catalytic center and electrons are transferred through reduced FMN to heme through electrostatic interactions
NADH
-
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NADPH
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
methanol
partially affects (10-20%) activity of the active recombinant enzyme
quinidine
-
1-aminobenzotriazole
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moderately prohibits spontaneous mutations of V79-hCYP2E1-hSULT1A1 cells. In combination with SULT1A1 inhibitor pentachlorophenol completely prohibits spontaneous mutations of V79-hCYP2E1-hSULT1A1 cells
17alpha-ethynylestradiol
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reactive intermediates of 17alpha-ethynylestradiol inactivate P450s in a NADPH-dependent mechanism-based manner by a combination of heme alkylation and apoprotein modification
8-methoxypsoralen
-
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anastrozole
-
profiling inhibition of probe 1 labeling of P450 19A1, inhibits labeling of P450 2C9 by probe 5
bifonazole
CYP19
cimetidine
-
specific inhibition
diethyldithiocarbamate
CYP2E1
Emulgen
-
a detergent that inactivates the enzyme at high concentrations
-
formestane
-
profiling inhibition of probe 1 labeling of P450 19A1, decreases probe 5 labeling of P450 2C19 and 1 labeling of P450 3A4
furafylline
ketoconazole
methanol
sulfaphenazole
ticlopidine
CYP2B6 and CYP2C19, 40% loss of sulfoxide formation. Decrease in fenthion-oxon formation by 71% and 64% at 0.005 mM or 0.1 mM fenthion concentrations, respectively, which is mainly attributable to CYP2B6
Tranylcypromine
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
anastrozole
-
increases labeling of P450 1A2 by probe 3 up to 175% of control values
NADPH-P450 reductase
-
supports the CYP3A4 activity through providing NADPH, mutations in NADPH-P450 reductase, identified in patients with disordered steroidogenesis/Antley-Bixler syndrome, reduce CYP3A4 activity. NADPH-P450 reductase mutants Y181D, A457H, Y459H, V492E and R616X loose more than 99% of CYP3A4 activity, while NADPH-P450 reductase mutations A287P, C569Y and V608F loose 60-85% activity
-
additional information
-
a drug-induced enzyme
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0016 - 0.131
fenthion
0.018
fenthion-sulfoxide
CYP2C19
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001
anastrozole
Homo sapiens
-
P450 19A1
0.00043
formestane
Homo sapiens
-
P450 19A1
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
CYP1A1 and CYP1A2
Manually annotated by BRENDA team
-
CYP1A1, CYP1A2 and CYP1B1
Manually annotated by BRENDA team
additional information
-
isozyme tissue-specific expression analysis, regulation by PPAR
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
CYP24A1 and CYP27A1
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
52000
-
x * 52000, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50
-
in absence of NADPH, the enzyme retains about 85% of the CYP functional activity
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partially by microsome preparation
-
recombinant enzyme from Escherichia coli by anion exchange chromatography and gel filtration to homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
baculovirus-infected insect cells expressing single c-DNA-derived CYPs
microsomes derived from baculovirus infected insect cells expressing CYP2D6
baculovirus-infected insect cells expressing single c-DNA-derived CYPs
coexpression of CYP1A2 with the Y459H and V492E mutant POR alleles in tBTC1A2_POR cell-models
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expression analysis of human CYPS, overvuew, expression in Escherichia coli without the N-terminal leader sequence
-
expression in V79 Chinese hamster fibroblasts and Hep-G2 cells, coexpression with N(O)-acetyltransferase or sulfotransferase 1A1-1
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expression of recombinant human P4502B6 and yeast reductase fused enzyme in transgenic tobacco plants, integration into the tobacco genome, functional expression of CYP1A1 and CYP1A1-yeast reductase fused enzyme in transgenic potato plants, genetic transformation is mediated by Agrobacterium tumefaciens
-
microsomes derived from baculovirus infected insect cells expressing CYP1A2
microsomes derived from baculovirus infected insect cells expressing CYP2B6
microsomes derived from baculovirus infected insect cells expressing CYP2C8
microsomes derived from baculovirus infected insect cells expressing CYP2C9, CYP2C19, CYP2E1, CYP3A4, or CYP19
microsomes derived from baculovirus infected insect cells expressing CYP3A5
microsomes derived from baculovirus infected insect cells expressing CYP3A7
recombinant cDNA P450s coexpressed with cytochrome P450 reductase in insect cell microsomes
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recombinant expression in Escherichia coli
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V79-hCYP2E1 (constructed by transfection of CYP2E1-expressing vector pSV together with vector pSV2neo containing a G418-selective marker into V79-Mz cells) and SULT1A1 expression vector introduced into this cell line
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
0.0001 mM dioxin treatment for 24, 48, and 72 h induces CYP1A1, CYP1A2 and CYP1B1 mRNA levels
-
beta-naphthoflavone (0.05 mM) causes a 9fold increase in CYP1A2-dependent activity and a 25fold increase in CYP1A2 mRNA expression in hepatocyte microsomes
-
dexamethasone (0.05 mM) and rifampicin (0.01 mM) increase CYP3A4 mRNA expression by a mean of 14fold in hepatocytes
-
in hepatocyte cultures, treatment with 0.05 mM Andrographis paniculata extract results in a slight decrease of CYP1A2 (30%) enzymatic activities
-
in hepatocyte cultures, treatment with 0.05 mM Andrographis paniculata extract results in a slight decrease of CYP2E1 (20%) enzymatic activities, whereas CYP2C9- and CYP3A4-dependent monooxygenase activities are significantly decreased by 40% and 60%, respectively. Andrographolide causes a 30% decrease in CYP2C9- and CYP3A4-dependent monooxygenase activities, which is not significant
-
mutations in NADPH-P450 reductase, identified in patients with disordered steroidogenesis/Antley-Bixler syndrome, reduce CYP3A4 activity. NADPH-P450 reductase mutants Y181D, A457H, Y459H, V492E and R616X loose more than 99% of CYP3A4 activity, while NADPH-P450 reductase mutations A287P, C569Y and V608F loose 60-85% activity
-
resveratrol inhibits dioxin-induced expression of CYP1A1, CYP1A2 and CYP1B1 by directly or indirectly inhibiting the recruitment of the transcription factors aryl hydrocarbon receptor and aryl hydrocarbon nuclear translocator to the xenobiotic response elements of the corresponding genes
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V79-hCYP2E1-hSULT1A1 cells contain a higher level of hCYP2E1 protein than the parental V79-hCYP2E1 line (by a factor of 3–4)
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
genetic variations, substantial effects of single nucleotide polymorphisms, e.g. CYP2D6 and CYP2C19 SNPs show large e.ects on metabolism of debrisoquine and (S)-mephenytoin, respectively, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
agriculture
-
enzyme expressed in Oryza sativa results in high tolerance to herbicides mefenacet, pyributicarb, amiprofos-methyl, trifluralin, pendimethalin, norflurazon, chlorotoluron and five chloroacetamides
biotechnology
most Cree anti-diabetic plant ethanolic extracts have the potential to affect CYP2C- and 3A4-mediated metabolism, and have the potential to affect the bioavailability and pharmacokinetics of conventional and traditional medicines during concomitant use, thus there is a potential risk of interactions if these traditional medicines are used with conventional therapeutic products, but several extracts may also have the potential to pharmacoenhance the activity of some medicines
medicine
-
plasma concentration of 4beta-hydroxycholesterol may be used as an endogenous marker of CYP3A activity. Concentration of 4beta-hydroxycholesterol increases with the number of active CYP3A5 alleles in Koreans, Swedes and Tanzanians