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Literature summary for 1.14.13.8 extracted from

  • Phillips, I.R.; Shephard, E.A.
    Flavin-containing monooxygenases: mutations, disease and drug response (2008), Trends Pharmacol. Sci., 29, 294-301.
    View publication on PubMed
Search for more literature for 1.14.13.8

Activating Compound

Activating Compound Comment Organism Structure
additional information FMO1 expression is increased in the myocardial tissue of patients with atrial fibrillation Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene FMO1, genes FMO1 to FMO4 are clustered on chromosome 1 at q24.3, along with a pseudogene FMO6P Homo sapiens
gene FMO2, genes FMO1 to FMO4 are clustered on chromosome 1 at q24.3, along with a pseudogene FMO6P Homo sapiens
gene FMO3, genes FMO1 to FMO4 are clustered on chromosome 1 at q24.3, along with a pseudogene FMO6P Homo sapiens

Protein Variants

Protein Variants Comment Organism
E158K naturally occuring single nucleotide polymorphism of FMO3 in Europeans and Asians, the mutation slightly affects enzyme activity, substrate-dependent reduced activity, phenotype, overview Homo sapiens
E158K/E308G naturally occuring single nucleotide polymorphism of FMO3 in Europeans and Asians, the mutation affects enzyme activity, substrate-dependent reduced activity, phenotype, overview Homo sapiens
E308G naturally occuring single nucleotide polymorphism of FMO3 in Europeans and Asians, the mutation slightly affects enzyme activity, substrate-dependent reduced activity, phenotype, overview Homo sapiens
L360P naturally occuring single nucleotide polymorphism of FMO3, the mutant shows increased activity Homo sapiens
additional information FMO3 is highly polymorphic, with as many as 15 nonsynonymous single nucleotide polymorphisms identified, many of which are present at relatively high frequency, several single nucleotide polymorphisms cause loss of function mutation of FMO3 resulting in trimethylaminuria or fish-odor-syndrome, the mutant enzymes are incapable of metabolizing trimethylamine to its non-odorous N-oxide, haplotypes and phenotypes, overview Homo sapiens
additional information most humans are homozygous for a nonsense mutation that inactivates FMO2. But a substantial proportion of sub-Saharan Africans express functional FMO2 and, thus, are predicted to respond differently to drugs and other foreign chemicals Homo sapiens
N61K naturally occuring single nucleotide polymorphism of FMO3, the mutant shows reduced activity Homo sapiens
N61S loss of function mutation of FMO3 results in trimethylaminuria or fish-odor-syndrome, the mutant enzyme is incapable of metabolizing trimethylamine to its non-odorous N-oxide, nuta this mutant is still active with methimazole, phenotype, overview Homo sapiens
Q472X naturally occuring single nucleotide polymorphism of FMO2, inactive mutant Homo sapiens
R205C naturally occuring single nucleotide polymorphism of FMO3, the mutant shows highly reduced activity Homo sapiens
R502X naturally occuring single nucleotide polymorphism of FMO1, the mutant shows substrate-dependent reduced activity compared to the wild-type enzyme Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
additional information the FMO1 gene is downregulated in the spinal cord of patients with the neurodegenerative disease amyotrophic lateral sclerosis Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
 Saccharomyces cerevisiae 5829
-
microsome
-
 Homo sapiens
-
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens drug metabolism, overview, enzyme mutations are involved in development of trimethylaminuria or fish-odor-syndrome, overview ?
-
 ?
additional information Homo sapiens drug metabolism, overview, most humans are homozygous for a nonsense mutation that inactivates FMO2. But a substantial proportion of sub-Saharan Africans express functional FMO2 and, thus, are predicted to respond differently to drugs and other foreign chemicals ?
-
 ?
additional information Homo sapiens drug metabolism, overview, the FMO1 gene is downregulated in the spinal cord of patients with the neurodegenerative disease amyotrophic lateral sclerosis, but is upregulated in the myocardial tissue of patients with atrial fibrillation ?
-
 ?
additional information Saccharomyces cerevisiae the substrate specificity of Saccharomyces cerevisiae FMO is more restricted than that of mammalian FMOs, reflecting its role in maintaining redox balance in the cell ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P31513 FMO3
-
Homo sapiens Q01740 FMO1
-
Homo sapiens Q99518 FMO2
-
Saccharomyces cerevisiae
-
-
-

Reaction

Reaction Comment Organism Reaction ID
N,N-dimethylaniline + NADPH + H+ + O2 = N,N-dimethylaniline N-oxide + NADP+ + H2O catalytic cycle, reaction mechanism and structure-function relationship, overview Homo sapiens
a

Source Tissue

Source Tissue Comment Organism Textmining
kidney adult and fetal, high expression level of FMO1 Homo sapiens
-
liver adult and fetal Homo sapiens
-
lung
-
 Homo sapiens
-
small intestine
-
 Homo sapiens
-
spinal cord reduced expression in amyotrophic lateral sclerosis Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
amphetamine + NADPH + H+ + O2 an antipsychotic agent, is converted to the hydroxylamine Homo sapiens ?
-
 ?
chlorpromazine + NADPH + H+ + O2 a dopemaine D2 antagonist Homo sapiens chlorpromazine N-oxide + NADP+ + H2O
-
 ?
clozapine + NADPH + H+ + O2 an antipsychotic agent, is converted to the N-oxide Homo sapiens clozapine N-oxide + NADP+ + H2O
-
 ?
deprenyl + NADPH + H+ + O2 a monoamine oxidase type B inhibitor, is converted to the hydroxylamine Homo sapiens ?
-
 ?
ethionamide + NADPH + H+ + O2 an antibiotic agent Homo sapiens ?
-
 ?
imipramine + NADPH + H+ + O2 an antidepressant, is converted to the N-oxide Homo sapiens imipramine N-oxide + NADP+ + H2O
-
 ?
itopride + NADPH + H+ + O2 a dopamine D2 receptor antagonist, is converted to the N-oxide Homo sapiens itopride N-oxide + NADP+ + H2O
-
 ?
methamphetamine + NADPH + H+ + O2 a psychostimulant, is converted to the hydroxylamine Homo sapiens ?
-
 ?
additional information drug metabolism, overview, enzyme mutations are involved in development of trimethylaminuria or fish-odor-syndrome, overview Homo sapiens ?
-
 ?
additional information drug metabolism, overview, most humans are homozygous for a nonsense mutation that inactivates FMO2. But a substantial proportion of sub-Saharan Africans express functional FMO2 and, thus, are predicted to respond differently to drugs and other foreign chemicals Homo sapiens ?
-
 ?
additional information drug metabolism, overview, the FMO1 gene is downregulated in the spinal cord of patients with the neurodegenerative disease amyotrophic lateral sclerosis, but is upregulated in the myocardial tissue of patients with atrial fibrillation Homo sapiens ?
-
 ?
additional information the substrate specificity of Saccharomyces cerevisiae FMO is more restricted than that of mammalian FMOs, reflecting its role in maintaining redox balance in the cell Saccharomyces cerevisiae ?
-
 ?
olopatadine + NADPH + H+ + O2 an antihistamininc drug, is converted to the N-oxide Homo sapiens olopatadine N-oxide + NADP+ + H2O
-
 ?
tamoxifen + NADPH + H+ + O2 an estrogen receptor modulator, is converted to the N-oxide Homo sapiens tamoxifen N-oxide + NADP+ + H2O
-
 ?
thiacetazone + NADPH + H+ + O2 an antibiotic agent, is converted to the sulfinic acid/carbodiimide Homo sapiens ?
-
 ?
thiacetazone + NADPH + H+ + O2 an antibiotic agent, is converted to the sulfinic acid/carbodiimide Homo sapiens thiacetazone N-oxide + NADP+ + H2O
-
 ?

Synonyms

Synonyms Comment Organism
FMO
-
 Saccharomyces cerevisiae
FMO1
-
 Homo sapiens
FMO2
-
 Homo sapiens
FMO3
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
FAD
-
 Saccharomyces cerevisiae
FAD
-
 Homo sapiens
NADPH
-
 Saccharomyces cerevisiae
NADPH
-
 Homo sapiens