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Information on EC 1.14.13.8 - flavin-containing monooxygenase and Organism(s) Rattus norvegicus and UniProt Accession P36365
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1.14.13.8 flavin-containing monooxygenaseIUBMB Comments
A flavoprotein. A broad spectrum monooxygenase that accepts substrates as diverse as hydrazines, phosphines, boron-containing compounds, sulfides, selenides, iodide, as well as primary, secondary and tertiary amines [3,4]. This enzyme is distinct from other monooxygenases in that the enzyme forms a relatively stable hydroperoxy flavin intermediate [4,5]. This microsomal enzyme generally converts nucleophilic heteroatom-containing chemicals and drugs into harmless, readily excreted metabolites. For example, N-oxygenation is largely responsible for the detoxification of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [2,6]
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Word Map
- 1.14.13.8
-
orbit
- methimazole
- trimethylamine
- xenobiotics
-
fenna-matthews-olson
- sulfoxide
-
n-oxygenation
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excitonic
-
s-oxidation
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initio
- bacteriochlorophyll
-
frontier
-
n-demethylation
- antenna
- tepidum
-
drug-metabolizing
- thioureas
- n-octylamine
- phenobarbital
-
cdna-expressed
-
light-harvesting
-
pigment-protein
- imipramine
- metyrapone
-
yucca
- chlorobium
-
baeyer-villiger
- cyp2c19
-
n-hydroxylation
-
diels-alder
-
hamiltonians
-
monooxygenation
-
sulfenic
-
p-450-dependent
- trimethylamine-n-oxide
- aestuarii
- cyp2a6
- nitrone
-
malodor
-
hartree-fock
- 1-aminobenzotriazole
-
ifies
-
piperonyl
- drug development
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
fmo, flavin-containing monooxygenase, flavin monooxygenase, flavin-dependent monooxygenase, flavin-containing monooxygenase 3, fad-containing monooxygenase, flavoprotein monooxygenase, hfmo3, flavin-containing mono-oxygenase, flavin-containing monooxygenase 1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dimethylaniline monooxygenase (N-oxide-forming)
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-
-
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dimethylaniline N-oxidase
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-
-
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dimethylaniline oxidase
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-
-
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DMA oxidase
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-
-
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FAD-containing monooxygenase
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-
-
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flavin monooxygenase
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-
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flavin-containing monooxygenase
FMO
FMO 1A1
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-
-
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FMO 1B1
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-
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FMO 1C1
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-
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FMO 1D1
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-
-
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FMO 1E1
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-
-
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FMO-I
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-
-
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FMO-II
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-
-
-
FMO1
FMO2
FMO3
FMO4
FMO5
mixed-function amine oxidase
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-
-
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N,N-dimethylaniline monooxygenase
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-
-
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oxygenase, dimethylaniline mono- (N-oxide-forming)
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-
-
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oxygenase, methylphenyltetrahydropyridine N-mono-
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-
-
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flavin-containing monooxygenase
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-
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FMO
-
-
-
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FMO1
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-
-
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FMO2
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-
-
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FMO3
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-
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FMO5
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
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-
-
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oxidation
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-
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reduction
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-
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SYSTEMATIC NAME
IUBMB Comments
N,N-dimethylaniline,NADPH:oxygen oxidoreductase (N-oxide-forming)
A flavoprotein. A broad spectrum monooxygenase that accepts substrates as diverse as hydrazines, phosphines, boron-containing compounds, sulfides, selenides, iodide, as well as primary, secondary and tertiary amines [3,4]. This enzyme is distinct from other monooxygenases in that the enzyme forms a relatively stable hydroperoxy flavin intermediate [4,5]. This microsomal enzyme generally converts nucleophilic heteroatom-containing chemicals and drugs into harmless, readily excreted metabolites. For example, N-oxygenation is largely responsible for the detoxification of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [2,6]
CAS REGISTRY NUMBER
COMMENTARY
117910-56-2
-
148848-55-9
-
37256-46-5
-
37256-73-8
-
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-methyl-4-phenyl-1,2,3,6-tetrahydropyridine + NADPH + H+ + O2
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine N-oxide + NADP+ + H2O
5-[[3-(dimethylamino)propyl]amino]-8-hydroxy-6H-[1,2,3]triazolo[4,5,1-de]acridin-6-one + NADPH + H+ + O2
5-[[3-(dimethylnitroryl)propyl]amino]-8-hydroxy-6H-[1,2,3]triazolo[4,5,1-de]acridin-6-one + NADP+ + H2O
-
i.e. C-1305
-
-
?
5-[[3-(dimethylamino)propyl]amino]-8-methoxy-6H-[1,2,3]triazolo[4,5,1-de]acridin-6-one + NADPH + H+ + O2
5-[[3-(dimethylnitroryl)propyl]amino]-8-methoxy-6H-[1,2,3]triazolo[4,5,1-de]acridin-6-one + NADP+ + H2O
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i.e. C-1299
-
-
?
L-methionine + NADPH + H+ + O2
methionine S-oxide + NADP+ + H2O
stereochemistry, overview
formation of 80% D-isomer
-
?
L-seleno-methionine + NADPH + O2
L-methionine seleno-oxide + NADP+ + H2O
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purified liver isozymes FMO1 and FMO3
-
-
?
methimazole + NADPH + H+ + O2
methimazole S-oxide + NADP+ + H2O
i.e. N-methyl-2-mercaptoimidazole
-
-
?
N,N-dimethylaniline + NADPH + O2
N,N-dimethylaniline N-oxide + NADP+ + H2O
-
-
-
-
?
S-allyl-L-cysteine + NADPH + H+ + O2
? + NADP+ + H2O
stereochemmistry, overview
-
-
?
S-benzyl-L-cysteine + NADPH + O2
S-benzyl-L-cysteine S-oxide + NADP+ + H2O
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isozyme FMO1
-
-
?
seleno-L-methionine + NADPH + H+ + O2
seleno-L-methionine Se-oxide + NADP+ + H2O
-
-
-
?
1,1-dimethylhydrazine + NADPH + O2
formaldehyde + CH3N2H3 + NADP+
-
-
-
?
1,1-dimethylhydrazine + NADPH + O2
formaldehyde + CH3N2H3 + NADP+
-
possibly, and other 1,1-disubstituted hydrazines
-
?
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine + NADPH + H+ + O2
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine N-oxide + NADP+ + H2O
-
-
-
-
?
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine + NADPH + H+ + O2
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine N-oxide + NADP+ + H2O
-
one of the predominant enzmyes responsible for the oxygenation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
-
-
?
hypotaurine + H2O + NAD+
taurine + NADH
-
metabolism of cysteine
-
?
L-methionine + NADPH + O2
L-methionine S-oxide + NADP+ + H2O
-
free and N-terminally peptide-bound L-methionine, no activity with modified peptide-bound methionine and with N-acetyl-L-methionine, isozymes FMO1-FMO4
stereospecificity for formation of the D-isomer, especially by isozyme FMO3
-
?
methimazole + NADPH + O2
N-methylmethimidazole-2-sulfinic acid + NADP+ + H2O
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-
-
-
?
methimazole + NADPH + O2
N-methylmethimidazole-2-sulfinic acid + NADP+ + H2O
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recombinant protein expressed in E. coli
-
-
?
tamoxifen + NADPH + O2
tamoxifen N-oxide + NADP+ + H2O
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tamoxifen N-oxygenation represents a detoxication pathway
-
-
?
tamoxifen + NADPH + O2
tamoxifen N-oxide + NADP+ + H2O
-
i.e. Z-(1-[4-(2-dimethyl-aminoethoxy)phenyl]-1,2-diphenyl-1-butene)
-
-
?
additional information
?
-
-
FMO oxygenates a number of drugs and xenobiotics containing a soft-nucleophile heteroatom, mostly sulfur- and nitrogen-containing xenobiotics, and is involved in detoxication
-
-
?
additional information
?
-
-
the enzyme plays an important role in drug metabolism, insulin itself has no effect on FMO1 activity in non-diabetic animals, but hepatic isozyme FMO1 and intestinal CYP3A activity are correlated with average blood glucose concentration in untreated diabetic rats, and insulin reduces CYP3A activity, thus also regulates FMO1 indirectly
-
-
?
additional information
?
-
-
stereoselectivity of purified isozymes FMO1 and FMO3, overview
-
-
?
additional information
?
-
-
isozyme FMO5 does not metabolize 5-[[3-(dimethylamino)propyl]amino]-8-hydroxy-6H-[1,2,3]triazolo[4,5,1-de]acridin-6-one (C-1305)
-
-
?
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
1,1-dimethylhydrazine + NADPH + O2
formaldehyde + CH3N2H3 + NADP+
-
possibly, and other 1,1-disubstituted hydrazines
-
?
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine + NADPH + H+ + O2
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine N-oxide + NADP+ + H2O
-
one of the predominant enzmyes responsible for the oxygenation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
-
-
?
hypotaurine + H2O + NAD+
taurine + NADH
-
metabolism of cysteine
-
?
tamoxifen + NADPH + O2
tamoxifen N-oxide + NADP+ + H2O
-
tamoxifen N-oxygenation represents a detoxication pathway
-
-
?
additional information
?
-
-
FMO oxygenates a number of drugs and xenobiotics containing a soft-nucleophile heteroatom, mostly sulfur- and nitrogen-containing xenobiotics, and is involved in detoxication
-
-
?
additional information
?
-
-
the enzyme plays an important role in drug metabolism, insulin itself has no effect on FMO1 activity in non-diabetic animals, but hepatic isozyme FMO1 and intestinal CYP3A activity are correlated with average blood glucose concentration in untreated diabetic rats, and insulin reduces CYP3A activity, thus also regulates FMO1 indirectly
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
insulin itself has no effect on FMO1 activity in non-diabetic animals
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
n-octylamine
-
allosteric activation of pig liver and mouse lung enzymes, not mouse, rabbit or rat liver enzymes
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
kinetics for kidney and liver enzymes, overview
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4 - 8.4
-
the activity is approximately twice as high at pH 8.4 as at pH 7.4
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
highest expression of FMO1 in the perivenous region
FMO3 is expressed in the renal collecting tubules, in renal medulla, and in renal glomerulus
FMO4 is expressed in the renal collecting tubules, in renal medulla, and in renal glomerulus
-
-
highest expression of FMO3 in the perivenous region
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
-
the flavin monooxygenase FMO1 contributes to metabolism of anti-tumor triazoloacridinone C-1305 (5-[[3-(dimethylamino)propyl]amino]-8-hydroxy-6H-[1,2,3]triazolo[4,5,1-de]acridin-6-one) in liver microsomes
physiological function
FMO3 plays an important role in kidney metabolism of xenobiotics containing sulfur and selenium atoms
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). FMO1_RAT
532
1
59825
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
56000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
frozen., 0.1 M Tris-HCl, pH 7.4, 36 h 50% loss of activity, loses total activity within 4 days
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
bacterial lipopolysaccharides lead to enzyme downregulation in the liver, as well as posttranslationally S-nitrosylation by nitric oxide
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Prough, R.A.; Freeman, P.C.; Hines, R.N.
The oxidation of hydrazine derivatives catalyzed by the purified liver microsomal FAD-containing monooxygenase
J. Biol. Chem.
256
4178-4184
1981
Mesocricetus auratus, Rattus norvegicus, Sus scrofa
Tynes, R.E.; Hodgson, E.
Catalytic activity and substrate specificity of the flavin-containing monooxygenase in microsomal systems: characterization of the hepatic, pulmonary and renal enzymes of the mouse, rabbit, and rat
Arch. Biochem. Biophys.
240
77-93
1985
Oryctolagus cuniculus, Mus musculus, Rattus norvegicus, Sus scrofa
Kawaji, A.; Miki, T.; Takabatake, E.
Partial purification and substrate specificity of flavin-containing monooxygenase from rat brain microsomes
Biol. Pharm. Bull.
18
1657-1659
1995
Rattus norvegicus
Lattard, V.; Buronfosse, T.; Lachuer, J.; Longin-Sauvageon, C.; Moulin, C.; Benoit, E.
Cloning, sequencing, tissue distribution, and heterologous expression of rat flavin-containing monooxygenase 3
Arch. Biochem. Biophys.
391
30-40
2001
Rattus norvegicus
Sumizu, K.
Oxidation of hypotaurine in rat liver
Biochim. Biophys. Acta
63
210 - 212
1962
Rattus norvegicus
Chiba, K.; Kobayashi, K.; Itoh, K.; Itoh, S.; Chiba, T.; Ishizaki, T.; Kamataki, T.
N-oxygenation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by the rat liver flavin-containing monooxygenase expressed in yeast cells
Eur. J. Pharmacol.
293
97-100
1995
Rattus norvegicus
Tsutsumi, H.; Katagi, M.; Nishikawa, M.; Tsuchihashi, H.; Kasuya, F.; Igarashi, K.
In vitro confirmation of selegiline N-oxidation by flavin-containing monooxygenase in rat microsome using LC-ESI MS
Biol. Pharm. Bull.
27
1572-1575
2004
Rattus norvegicus
Elfarra, A.A.; Krause, R.J.
Potential roles of flavin-containing monooxygenases in sulfoxidation reactions of L-methionine, N-acetyl-L-methionine and peptides containing L-methionine
Biochim. Biophys. Acta
1703
183-189
2005
Oryctolagus cuniculus, Homo sapiens, Rattus norvegicus
Krueger, S.K.; Vandyke, J.E.; Williams, D.E.; Hines, R.N.
The role of flavin-containing monooxygenase (FMO) in the metabolism of tamoxifen and other tertiary amines
Drug Metab. Rev.
38
139-147
2006
Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Borbas, T.; Benko, B.; Dalmadi, B.; Szabo, I.; Tihanyi, K.
Insulin in flavin-containing monooxygenase regulation. Flavin-containing monooxygenase and cytochrome P450 activities in experimental diabetes
Eur. J. Pharm. Sci.
28
51-58
2006
Rattus norvegicus
Mitchell, S.
Flavin mono-oxygenase (FMO) - The other oxidase
Curr. Drug Metab.
9
280-284
2008
Oryctolagus cuniculus, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Novick, R.M.; Elfarra, A.A.
Purification and characterization of flavin-containing monooxygenase isoform 3 from rat kidney microsomes
Drug Metab. Dispos.
36
2468-2474
2008
Rattus norvegicus (Q9EQ76)
Novick, R.M.; Mitzey, A.M.; Brownfield, M.S.; Elfarra, A.A.
Differential localization of flavin-containing monooxygenase (FMO) isoforms 1, 3, and 4 in rat liver and kidney and evidence for expression of FMO4 in mouse, rat, and human liver and kidney microsomes
J. Pharmacol. Exp. Ther.
329
1148-1155
2009
Homo sapiens, Homo sapiens (P31512), Mus musculus, Rattus norvegicus (P36365), Rattus norvegicus (Q8K4B7), Rattus norvegicus (Q9EQ76)
Fedejko-Kap, B.; Niemira, M.; Radominska-Pandya, A.; Mazerska, Z.
Flavin monooxygenases, FMO1 and FMO3, not cytochrome P450 isoenzymes, contribute to metabolism of anti-tumour triazoloacridinone, C-1305, in liver microsomes and HepG2 cells
Xenobiotica
41
1044-1055
2011
Rattus norvegicus, Homo sapiens (Q01740), Homo sapiens (Q9HA79), Homo sapiens
Taniguchi-Takizawa, T.; Shimizu, M.; Kume, T.; Yamazaki, H.
Benzydamine N-oxygenation as an index for flavin-containing monooxygenase activity and benzydamine N-demethylation by cytochrome P450 enzymes in liver microsomes from rats, dogs, monkeys, and humans
Drug Metab. Pharmacokinet.
30
64-69
2015
Canis lupus familiaris, Macaca fascicularis, Homo sapiens, Rattus norvegicus
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