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Literature summary for 1.14.13.8 extracted from

  • Krueger, S.K.; Williams, D.E.
    Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism (2005), Pharmacol. Ther., 106, 357-387.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.14.13.8

Activating Compound

Activating Compound Comment Organism Structure
additional information FMO is not induced by xenobiotics Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
genes FMO1-FMO6, FMO6 is a pseudogene, the genes are organized in two clusters chromosome 1, one of which resides on the long arm of chromosome 1 at q23 –25, the second cluster is composed of 3 genes, that are not pseudogenes Mus musculus
genes FMO1-FMO6, FMO6 is a pseudogene, the genes are organized in two clusters chromosome 1, one of which resides on the long arm of chromosome 1 at q23 –25, the second cluster is composed of 5 pseudogenes Homo sapiens

Protein Variants

Protein Variants Comment Organism
D132H natural genetic variant of isozyme FMO2, substrate specificity, overview Homo sapiens
E132H natural genetic variant of isozyme FMO2, substrate specificity, overview Homo sapiens
E132H/E158K natural genetic variant of isozyme FMO2, substrate specificity, overview Homo sapiens
E158K natural genetic variant of isozymes FMO2 and FMO3, substrate specificity, overview Homo sapiens
E158K/E308G natural genetic variant of isozyme FMO2, substrate specificity, overview Homo sapiens
E308G natural genetic variant of isozyme FMO2, substrate specificity, overview Homo sapiens
F510X natural genetic variant of isozyme FMO2, substrate specificity, overview Homo sapiens
H97Q natural genetic variant of isozyme FMO1, substrate specificity, overview Homo sapiens
I303T natural genetic variant of isozyme FMO1, substrate specificity, overview Homo sapiens
I303V natural genetic variant of isozyme FMO1, substrate specificity, overview Homo sapiens
L360P natural genetic variant of isozyme FMO2, substrate specificity, overview Homo sapiens
additional information three of the five expressed human FMO genes, FMO1, FMO2 and FMO3, exhibit genetic polymorphisms, overview Homo sapiens
R502X natural genetic variant of isozyme FMO1, substrate specificity, overview Homo sapiens
V257M natural genetic variant of isozyme FMO3, substrate specificity, overview Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
additional information the lung isozyme is resistant to detergent inhibition Oryctolagus cuniculus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information
-
 Homo sapiens
additional information
-
 additional information
-
 Sus scrofa
additional information
-
 additional information
-
 Oryctolagus cuniculus

Localization

Localization Comment Organism GeneOntology No. Textmining
microsome
-
 Homo sapiens
-
-
microsome
-
 Sus scrofa
-
-
microsome
-
 Oryctolagus cuniculus
-
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
10-N-(n-octylamino)-2-(trifluoromethyl) phenothiazine + NADPH + O2 Homo sapiens
-
 10-N-(n-octylamino)-2-(trifluoromethyl) phenothiazine N-oxide + NADP+ + H2O
-
 ?
amphetamine + NADPH + O2 Homo sapiens
-
 amphetamine N-oxide + NADP+ + H2O
-
 ?
cysteamine + NADPH + O2 Mus musculus
-
 cysteamine N-oxide + NADP+ + H2O
-
 ?
cysteamine + NADPH + O2 Homo sapiens
-
 cysteamine N-oxide + NADP+ + H2O
-
 ?
cysteamine + NADPH + O2 Sus scrofa
-
 cysteamine N-oxide + NADP+ + H2O
-
 ?
cysteamine + NADPH + O2 Oryctolagus cuniculus
-
 cysteamine N-oxide + NADP+ + H2O
-
 ?
dihydrolipoic acid + NADPH + O2 Sus scrofa
-
 ?
-
 ?
fenthion + NADPH + O2 Homo sapiens
-
 fenthion sulfoxide + NADP+ + H2O
-
 ?
imipramine + NADPH + O2 Homo sapiens
-
 ?
-
 ?
L-methionine + NADPH + O2 Homo sapiens
-
 L-methionine S-oxide + NADP+ + H2O
-
 ?
L-methionine + NADPH + O2 Sus scrofa
-
 L-methionine S-oxide + NADP+ + H2O
-
 ?
L-methionine + NADPH + O2 Oryctolagus cuniculus
-
 L-methionine S-oxide + NADP+ + H2O
-
 ?
lipoic acid + NADPH + O2 Homo sapiens
-
 ?
-
 ?
lipoic acid + NADPH + O2 Sus scrofa
-
 ?
-
 ?
methimazole + NADPH + O2 Homo sapiens
-
 ?
-
 ?
methyl 4-tolyl sulfide + NADPH + O2 Homo sapiens
-
 methyl 4-tolyl sulfoxide + NADP+ + H2O
-
 ?
additional information Homo sapiens nitrogen- and sulfur-containing endogenous substrates and physiologic functions, FMO is not induced by xenobiotics, isozyme FMO3 mutant alleles contribute to the disease known as trimethylaminuria, the enzyme is involved in detoxification and drug metabolism, overview, expression of FMO5 is markedly down-regulated in the liver of humans with type II diabetes, patients diagnosed with atrial fibrillation document a significant increase in the expression of FMO1, FMO may be associated with sideroblastic anemia, FMO3 mutations lead to trimethylaminuria, detailed overview ?
-
 ?
additional information Sus scrofa nitrogen- and sulfur-containing endogenous substrates and physiologic functions, the enzyme is involved in detoxification and drug metabolism, overview ?
-
 ?
additional information Oryctolagus cuniculus nitrogen- and sulfur-containing endogenous substrates and physiologic functions, the enzyme is involved in detoxification and drug metabolism, overview ?
-
 ?
additional information Mus musculus nitrogen- and sulfur-containing endogenous substrates and physiologic functions, the enzyme is involved in detoxification and drug metabolism, overview, hepatic total FMO activity is enhanced in mouse models of type I and type II diabetes ?
-
 ?
N,N-dimethylaniline + NADPH + O2 Mus musculus
-
 N,N-dimethylaniline N-oxide + NADP+ + H2O
-
 ?
N,N-dimethylaniline + NADPH + O2 Homo sapiens
-
 N,N-dimethylaniline N-oxide + NADP+ + H2O
-
 ?
N,N-dimethylaniline + NADPH + O2 Sus scrofa
-
 N,N-dimethylaniline N-oxide + NADP+ + H2O
-
 ?
N,N-dimethylaniline + NADPH + O2 Oryctolagus cuniculus
-
 N,N-dimethylaniline N-oxide + NADP+ + H2O
-
 ?
phenethylamine + NADPH + O2 Homo sapiens isozyme FMO3 phenethylamine N-oxide + NADP+ + H2O
-
 ?
ranitidine + NADPH + O2 Homo sapiens
-
 ?
-
 ?
S-farnesylcysteine + NADPH + O2 Sus scrofa
-
 S-farnesylcysteine S-oxide + NADP+ + H2O
-
 ?
S-farnesylcysteine methyl ester + NADPH + O2 Sus scrofa
-
 ?
-
 ?
trimethylamine + NADPH + O2 Mus musculus
-
 trimethylamine N-oxide + NADP+ + H2O
-
 ?
trimethylamine + NADPH + O2 Homo sapiens
-
 trimethylamine N-oxide + NADP+ + H2O
-
 ?
trimethylamine + NADPH + O2 Sus scrofa
-
 trimethylamine N-oxide + NADP+ + H2O
-
 ?
tyramine + NADPH + O2 Homo sapiens
-
 tyramine N-oxide + NADP+ + H2O
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
 genes FMO1-FMO6, FMO6 is a pseudogene
-
Mus musculus
-
-
-
Oryctolagus cuniculus
-
 tissue-specific isozymes
-
Sus scrofa
-
-
-

Purification (Commentary)

Purification (Comment) Organism
from liver microsomes Sus scrofa
isozyme from lung microsomes Oryctolagus cuniculus

Reaction

Reaction Comment Organism Reaction ID
N,N-dimethylaniline + NADPH + H+ + O2 = N,N-dimethylaniline N-oxide + NADP+ + H2O catalytic cycle and catalytic reaction mechanism, structure-function relationship, FMO oxygenates drugs and xenobiotics containing a soft nucleophile, usually nitrogen or sulfur, utilizing the reducing equivalents of NADPH to reduce 1 atom of molecular oxygen to water, while the other atom is used to oxidize the substrate, FMO does not require a reductase to transfer electrons from NADPH, substrate binding has no effect on velocity, formation of a peroxyflavin intermediate Mus musculus
a
N,N-dimethylaniline + NADPH + H+ + O2 = N,N-dimethylaniline N-oxide + NADP+ + H2O catalytic cycle and catalytic reaction mechanism, structure-function relationship, FMO oxygenates drugs and xenobiotics containing a soft nucleophile, usually nitrogen or sulfur, utilizing the reducing equivalents of NADPH to reduce 1 atom of molecular oxygen to water, while the other atom is used to oxidize the substrate, FMO does not require a reductase to transfer electrons from NADPH, substrate binding has no effect on velocity, formation of a peroxyflavin intermediate Homo sapiens
a
N,N-dimethylaniline + NADPH + H+ + O2 = N,N-dimethylaniline N-oxide + NADP+ + H2O catalytic cycle and catalytic reaction mechanism, structure-function relationship, FMO oxygenates drugs and xenobiotics containing a soft nucleophile, usually nitrogen or sulfur, utilizing the reducing equivalents of NADPH to reduce 1 atom of molecular oxygen to water, while the other atom is used to oxidize the substrate, FMO does not require a reductase to transfer electrons from NADPH, substrate binding has no effect on velocity, formation of a peroxyflavin intermediate Sus scrofa
a
N,N-dimethylaniline + NADPH + H+ + O2 = N,N-dimethylaniline N-oxide + NADP+ + H2O catalytic cycle and catalytic reaction mechanism, structure-function relationship, FMO oxygenates drugs and xenobiotics containing a soft nucleophile, usually nitrogen or sulfur, utilizing the reducing equivalents of NADPH to reduce 1 atom of molecular oxygen to water, while the other atom is used to oxidize the substrate, FMO does not require a reductase to transfer electrons from NADPH, substrate binding has no effect on velocity, formation of a peroxyflavin intermediate Oryctolagus cuniculus
a

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
 Homo sapiens
-
liver
-
 Mus musculus
-
liver
-
 Oryctolagus cuniculus
-
liver isozyme FMO1 Sus scrofa
-
liver isozyme FMO3 Homo sapiens
-
lung isozyme FMO2 Homo sapiens
-
lung lung isozyme FMO2 Oryctolagus cuniculus
-
additional information the lung isozyme FMO2 is distinct from the liver isozyme in having high activity toward primary alkyl amines, restricted substrate specificity related to steric properties, resistance to detergent inhibition and enhanced thermal stability Oryctolagus cuniculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
10-(N,N-dimethylaminoalkyl)-2-(trifluoromethyl) phenothiazines + NADPH + O2 with the alkyl side chain varying in length from 2 to 7 carbons, liver isozyme FMO1 Sus scrofa ?
-
 ?
10-(N,N-dimethylaminoalkyl)-2-(trifluoromethyl) phenothiazines + NADPH + O2 with the alkyl side chain varying in length from 5 to 7 carbons, no activity with shorter side chains by isozyme FMO2 Oryctolagus cuniculus ?
-
 ?
10-N-(n-octylamino)-2-(trifluoromethyl) phenothiazine + NADPH + O2
-
 Homo sapiens 10-N-(n-octylamino)-2-(trifluoromethyl) phenothiazine N-oxide + NADP+ + H2O
-
 ?
10-N-(n-octylamino)-2-(trifluoromethyl) phenothiazine + NADPH + O2 formation of the cis-oxime Homo sapiens 10-N-(n-octylamino)-2-(trifluoromethyl) phenothiazine N-oxide + NADP+ + H2O
-
 ?
amphetamine + NADPH + O2
-
 Homo sapiens amphetamine N-oxide + NADP+ + H2O
-
 ?
chlorpromazine + NADPH + O2 liver isozyme FMO1 Sus scrofa ?
-
 ?
cysteamine + NADPH + O2
-
 Mus musculus cysteamine N-oxide + NADP+ + H2O
-
 ?
cysteamine + NADPH + O2
-
 Homo sapiens cysteamine N-oxide + NADP+ + H2O
-
 ?
cysteamine + NADPH + O2
-
 Sus scrofa cysteamine N-oxide + NADP+ + H2O
-
 ?
cysteamine + NADPH + O2
-
 Oryctolagus cuniculus cysteamine N-oxide + NADP+ + H2O
-
 ?
dihydrolipoic acid + NADPH + O2
-
 Sus scrofa ?
-
 ?
fenthion + NADPH + O2
-
 Homo sapiens fenthion sulfoxide + NADP+ + H2O
-
 ?
fenthion + NADPH + O2 i.e. O,O-dimethyl O-4-methylthio-m-tolyl phosphorothioate, isozymes FMO1 and FMO3, stereospecifc product formation, overview Homo sapiens fenthion sulfoxide + NADP+ + H2O
-
 ?
imipramine + NADPH + O2
-
 Homo sapiens ?
-
 ?
imipramine + NADPH + O2 liver isozyme FMO1 Sus scrofa ?
-
 ?
L-methionine + NADPH + O2
-
 Homo sapiens L-methionine S-oxide + NADP+ + H2O
-
 ?
L-methionine + NADPH + O2
-
 Sus scrofa L-methionine S-oxide + NADP+ + H2O
-
 ?
L-methionine + NADPH + O2
-
 Oryctolagus cuniculus L-methionine S-oxide + NADP+ + H2O
-
 ?
lipoic acid + NADPH + O2
-
 Homo sapiens ?
-
 ?
lipoic acid + NADPH + O2
-
 Sus scrofa ?
-
 ?
methimazole + NADPH + O2
-
 Homo sapiens ?
-
 ?
methyl 4-tolyl sulfide + NADPH + O2
-
 Homo sapiens methyl 4-tolyl sulfoxide + NADP+ + H2O
-
 ?
additional information nitrogen- and sulfur-containing endogenous substrates and physiologic functions, FMO is not induced by xenobiotics, isozyme FMO3 mutant alleles contribute to the disease known as trimethylaminuria, the enzyme is involved in detoxification and drug metabolism, overview, expression of FMO5 is markedly down-regulated in the liver of humans with type II diabetes, patients diagnosed with atrial fibrillation document a significant increase in the expression of FMO1, FMO may be associated with sideroblastic anemia, FMO3 mutations lead to trimethylaminuria, detailed overview Homo sapiens ?
-
 ?
additional information nitrogen- and sulfur-containing endogenous substrates and physiologic functions, the enzyme is involved in detoxification and drug metabolism, overview Sus scrofa ?
-
 ?
additional information nitrogen- and sulfur-containing endogenous substrates and physiologic functions, the enzyme is involved in detoxification and drug metabolism, overview Oryctolagus cuniculus ?
-
 ?
additional information nitrogen- and sulfur-containing endogenous substrates and physiologic functions, the enzyme is involved in detoxification and drug metabolism, overview, hepatic total FMO activity is enhanced in mouse models of type I and type II diabetes Mus musculus ?
-
 ?
additional information FMO oxygenates drugs and xenobiotics containing a soft nucleophile, usually nitrogen or sulfur, isozyme substrate specificity, detailed overview, no activity with 1,3-diphenylthiourea Homo sapiens ?
-
 ?
additional information FMO oxygenates oxygenates a wide range of sulfur- and nitrogen-containing xenobiotics and, in some cases, also oxygenates selenium, iodine, boron, phosphorus and even carbon, it oxidizes drugs and xenobiotics containing a soft nucleophile, usually nitrogen or sulfur, utilizing the reducing equivalents of NADPH to reduce 1 atom of molecular oxygen to water, while the other atom is used to oxidize the substrate, FMO does not require a reductase to transfer electrons from NADPH, liver isozyme FMO1 shows a very promiscuous substrate specificity, isozyme substrate specificity, detailed overview Sus scrofa ?
-
 ?
additional information the lung isozyme is distinct from the liver isozyme in having high activity toward primary alkyl amines, restricted substrate specificity related to steric properties, resistance to detergent inhibition and enhanced thermal stability, and restricted substrate access, no activity of the lung isozyme with 1,3-diphenylthiourea, chlorpromazine and imipramine by isozyme FMO2, isozyme substrate specificity, detailed overview Oryctolagus cuniculus ?
-
 ?
N,N-dimethylaniline + NADPH + O2
-
 Mus musculus N,N-dimethylaniline N-oxide + NADP+ + H2O
-
 ?
N,N-dimethylaniline + NADPH + O2
-
 Homo sapiens N,N-dimethylaniline N-oxide + NADP+ + H2O
-
 ?
N,N-dimethylaniline + NADPH + O2
-
 Sus scrofa N,N-dimethylaniline N-oxide + NADP+ + H2O
-
 ?
N,N-dimethylaniline + NADPH + O2
-
 Oryctolagus cuniculus N,N-dimethylaniline N-oxide + NADP+ + H2O
-
 ?
naphthylthiourea + NADPH + O2 isozyme FMO2 Homo sapiens naphthylthiourea S-oxide + NADP+ + H2O
-
 ?
naphthylthiourea + NADPH + O2 isozyme FMO2 Oryctolagus cuniculus naphthylthiourea S-oxide + NADP+ + H2O
-
 ?
phenethylamine + NADPH + O2 isozyme FMO3 Homo sapiens phenethylamine N-oxide + NADP+ + H2O
-
 ?
phenylthiourea + NADPH + O2 isozyme FMO2 Homo sapiens phenylthiourea S-oxide + NADP+ + H2O
-
 ?
phenylthiourea + NADPH + O2 isozyme FMO2 Oryctolagus cuniculus phenylthiourea S-oxide + NADP+ + H2O
-
 ?
ranitidine + NADPH + O2
-
 Homo sapiens ?
-
 ?
S-farnesylcysteine + NADPH + O2
-
 Sus scrofa S-farnesylcysteine S-oxide + NADP+ + H2O
-
 ?
S-farnesylcysteine methyl ester + NADPH + O2
-
 Sus scrofa ?
-
 ?
S-farnesylcysteine methyl ester + NADPH + O2
-
 Sus scrofa S-farnesylcysteine S-oxide methyl ester + NADP+ + H2O
-
 ?
sulindac sulfide + NADPH + O2
-
 Sus scrofa sulindac + NADP+ + H2O
-
 ?
thiourea + NADPH + O2
-
 Sus scrofa thiourea S-oxide + NADP+ + H2O
-
 ?
thiourea + NADPH + O2 isozyme FMO2 Homo sapiens thiourea S-oxide + NADP+ + H2O
-
 ?
trifluoroperazine + NADPH + O2
-
 Sus scrofa ?
-
 ?
trimethylamine + NADPH + O2
-
 Mus musculus trimethylamine N-oxide + NADP+ + H2O
-
 ?
trimethylamine + NADPH + O2
-
 Homo sapiens trimethylamine N-oxide + NADP+ + H2O
-
 ?
trimethylamine + NADPH + O2
-
 Sus scrofa trimethylamine N-oxide + NADP+ + H2O
-
 ?
tyramine + NADPH + O2
-
 Homo sapiens tyramine N-oxide + NADP+ + H2O
-
 ?

Subunits

Subunits Comment Organism
More structure motifs, overview, structural modeling Mus musculus
More structure motifs, overview, structural modeling Homo sapiens
More structure motifs, overview, structural modeling Sus scrofa
More structure motifs, overview, structural modeling Oryctolagus cuniculus

Synonyms

Synonyms Comment Organism
FMO
-
 Mus musculus
FMO
-
 Homo sapiens
FMO
-
 Sus scrofa
FMO
-
 Oryctolagus cuniculus
More the enzyme belongs to the human FMO functional gene family Homo sapiens

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
additional information
-
 the lung isozyme shows high thermal stability as the liver isozyme Oryctolagus cuniculus

Cofactor

Cofactor Comment Organism Structure
FAD one molecule per enzyme molecule, binding motif Mus musculus
FAD one molecule per enzyme molecule, binding motif Homo sapiens
FAD one molecule per enzyme molecule, binding motif Sus scrofa
FAD one molecule per enzyme molecule, binding motif Oryctolagus cuniculus
additional information the enzyme contains no heme Mus musculus
additional information the enzyme contains no heme Homo sapiens
additional information the enzyme contains no heme Sus scrofa
additional information the enzyme contains no heme Oryctolagus cuniculus
NADPH binding structure Mus musculus
NADPH binding structure Homo sapiens
NADPH binding structure Sus scrofa
NADPH binding structure Oryctolagus cuniculus