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Literature summary extracted from
- Some distinctions between flavin-containing and cytochrome P450 monooxygenases (2005), Biochem. Biophys. Res. Commun., 338, 599-604.
Activating Compound
| EC Number | Activating Compound | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.14.13.8 | additional information | FMO is not induced or readily inhibited by drugs in general in contrast to cytochrome P450 monooxygenases | Homo sapiens | |
| 1.14.14.1 | additional information | a drug-induced enzyme | Homo sapiens |
Application
| EC Number | Application | Comment | Organism |
|---|---|---|---|
| 1.14.13.8 | drug development | the enzyme is not affected by drugs in contrast to cytochrome P450 monooxygenases, EC 1.14.14.1, by incorporating FMO detoxication pathways into drug candidates, more drug-like materials may emerge | Homo sapiens |
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 1.14.13.8 | additional information | occuring single nucleotide polymorphisms are associated with dramatic functional differences in selective functional enzyme activity, overview | Homo sapiens |
| 1.14.14.1 | 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 | Homo sapiens |
General Stability
| EC Number | General Stability | Organism |
|---|---|---|
| 1.14.13.8 | NADPH stabilizes the enzyme | Homo sapiens |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.14.13.8 | additional information | FMO is not induced or readily inhibited by drugs in general in contrast to cytochrome P450 monooxygenases | Homo sapiens | |
| 1.14.14.1 | cimetidine | specific inhibition | Homo sapiens |  |
| 1.14.14.1 | Emulgen | a detergent that inactivates the enzyme at high concentrations | Homo sapiens |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 1.14.13.8 | microsome | the highly hydrophobic FMO shows multiple internal sites of membrane association | Homo sapiens | - |
- |
| 1.14.14.1 | microsome | - |
Homo sapiens | - |
- |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.14.13.8 | (S)-nicotine + NADPH + O2 | Homo sapiens | (S)-nicotine N-1'-oxygenation | (S)-nicotine N1-oxide + NADP+ + H2O | - |
? | |
| 1.14.13.8 | benzylamine + [reduced NADPH-hemoprotein reductase] + O2 | Homo sapiens | - |
benzylamine N-oxide + [oxidized NADPH-hemoprotein reductase] + H2O | - |
? | |
| 1.14.13.8 | cimetidine + NADPH + O2 | Homo sapiens | - |
cimetidine S-oxide + NADP+ + H2O | - |
? | |
| 1.14.13.8 | clozapine + NADPH + O2 | Homo sapiens | - |
? | - |
? | |
| 1.14.13.8 | itopride + NADPH + O2 | Homo sapiens | - |
? | - |
? | |
| 1.14.13.8 | additional information | Homo sapiens | enzyme regulation, overview | ? | - |
? | |
| 1.14.13.8 | N,N-dimethylaniline + NADPH + O2 | Homo sapiens | - |
N,N-dimethylaniline N-oxide + NADP+ + H2O | - |
? | |
| 1.14.13.8 | ranitidine + NADPH + O2 | Homo sapiens | - |
? | - |
? | |
| 1.14.13.8 | trimethylamine + NADPH + O2 | Homo sapiens | - |
trimethylamine N-oxide + NADP+ + H2O | - |
? | |
| 1.14.14.1 | additional information | Homo sapiens | in humans, CYP3A4 appears to be the dominant CYP and contributes to over 60% of the metabolism of drugs, the Ah receptor is important in CYP1A1 regulation, a number of mechanisms occur to regulate CYP including enhancement of mRNA stability, modulation of heme degradation, enzyme phosphorylation, and protein-protein interactions | ? | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 1.14.13.8 | Homo sapiens | - |
isozymes FMO1-FMO5 | - |
| 1.14.14.1 | Homo sapiens | - |
- |
- |
Posttranslational Modification
| EC Number | Posttranslational Modification | Comment | Organism |
|---|---|---|---|
| 1.14.13.8 | glycoprotein | FMO1 is selectively N-glycosylated at Asn120, N-glycosylation is not essential for functional activity | Homo sapiens |
Reaction
| EC Number | Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|---|
| 1.14.13.8 | N,N-dimethylaniline + NADPH + H+ + O2 = N,N-dimethylaniline N-oxide + NADP+ + H2O | catalytic reaction mechanism, structure-function relationship, FMO oxygenates soft nucleophiles, and converts lipophilic compounds into more hydrophilic metabolites, the first step for FMO is reduction of the FAD by NADPH, the next step is formation of a C4a-hydroperoxy flavin by addition of molecular oxygen to the reduced FAD, when the substrate is accepted by FMO the enzyme is already in an active form, the protein environment of FMO apparently protects the hydroperoxy flavin from decomposing, conserving NADPH, and affording an effcient two-electron oxygenating agent for nucleophiles with the appropriate size and shape | Homo sapiens | |
| 1.14.14.1 | RH + [reduced NADPH-hemoprotein reductase] + O2 = ROH + [oxidized NADPH-hemoprotein reductase] + H2O | catalytic reaction mechanism, structure-function relationship, CYP can oxidize non-nucleophilic substrates, CYP possesses genetic variability that may contribute to inter-individual variability observed for drug metabolism, the first step of CYP is the addition of substrate to the enzyme followed by electron transfer from the flavoprotein NADPH-CYP reductase to the substrate-bound CYP, then electrons flow to the FMN prosthetic group and then sequentially to the CYP to ultimately afford a reactive iron-oxo species, although other peroxy forms of the hemoprotein are proposed also to be oxidants involved in CYP-dependent metabolism | Homo sapiens |
Source Tissue
| EC Number | Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|---|
| 1.14.13.8 | liver | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.14.13.8 | (S)-nicotine + NADPH + O2 | (S)-nicotine N-1'-oxygenation | Homo sapiens | (S)-nicotine N1-oxide + NADP+ + H2O | - |
? | |
| 1.14.13.8 | benzylamine + [reduced NADPH-hemoprotein reductase] + O2 | - |
Homo sapiens | benzylamine N-oxide + [oxidized NADPH-hemoprotein reductase] + H2O | - |
? | |
| 1.14.13.8 | cimetidine + NADPH + O2 | - |
Homo sapiens | cimetidine S-oxide + NADP+ + H2O | - |
? | |
| 1.14.13.8 | clozapine + NADPH + O2 | - |
Homo sapiens | ? | - |
? | |
| 1.14.13.8 | itopride + NADPH + O2 | - |
Homo sapiens | ? | - |
? | |
| 1.14.13.8 | additional information | enzyme regulation, overview | Homo sapiens | ? | - |
? | |
| 1.14.13.8 | additional information | FMO oxygenates soft nucleophiles, and converts lipophilic compounds into more hydrophilic metabolites, potential adverse drug-drug interactions are minimized for drugs prominently metabolized by FMO, substrate specificities of isozmes, overview | Homo sapiens | ? | - |
? | |
| 1.14.13.8 | N,N-dimethylaniline + NADPH + O2 | - |
Homo sapiens | N,N-dimethylaniline N-oxide + NADP+ + H2O | - |
? | |
| 1.14.13.8 | ranitidine + NADPH + O2 | - |
Homo sapiens | ? | - |
? | |
| 1.14.13.8 | trimethylamine + NADPH + O2 | - |
Homo sapiens | trimethylamine N-oxide + NADP+ + H2O | - |
? | |
| 1.14.14.1 | (S)-nicotine + [reduced NADPH-hemoprotein reductase] + O2 | substrate of CYP3A4, the reaction involves electron transfer via FMN | Homo sapiens | ? | - |
? | |
| 1.14.14.1 | dimethylaniline + [reduced NADPH-hemoprotein reductase] + O2 | substrate of CYP3A4 | Homo sapiens | ? | - |
? | |
| 1.14.14.1 | additional information | in humans, CYP3A4 appears to be the dominant CYP and contributes to over 60% of the metabolism of drugs, the Ah receptor is important in CYP1A1 regulation, a number of mechanisms occur to regulate CYP including enhancement of mRNA stability, modulation of heme degradation, enzyme phosphorylation, and protein-protein interactions | Homo sapiens | ? | - |
? | |
| 1.14.14.1 | additional information | CYP mainly catalyzes C-H abstraction but also oxidizes nitrogen- and sulfur-containing compounds and generally converts lipophilic compounds into more hydrophilic metabolites | Homo sapiens | ? | - |
? | |
Subunits
| EC Number | Subunits | Comment | Organism |
|---|---|---|---|
| 1.14.14.1 | More | structure-function relationship | Homo sapiens |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 1.14.13.8 | flavin-containing-monooxygenase | - |
Homo sapiens |
| 1.14.13.8 | FMO | - |
Homo sapiens |
| 1.14.14.1 | Cyp | - |
Homo sapiens |
| 1.14.14.1 | CYP3A4 | - |
Homo sapiens |
| 1.14.14.1 | cytochrome P450 monooxygenase | - |
Homo sapiens |
Temperature Stability [°C]
| EC Number | Temperature Stability Minimum [°C] | Temperature Stability Maximum [°C] | Comment | Organism |
|---|---|---|---|---|
| 1.14.13.8 | 50 | - |
the enzyme is unstable in absence of NADPH | Homo sapiens |
| 1.14.14.1 | 50 | - |
in absence of NADPH, the enzyme retains about 85% of the CYP functional activity | Homo sapiens |
pH Optimum
| EC Number | pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|---|
| 1.14.13.8 | 9 | 10 | - |
Homo sapiens |
| 1.14.14.1 | 7.4 | - |
inactive at pH 8.49.4 | Homo sapiens |
Cofactor
| EC Number | Cofactor | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.14.13.8 | FAD | - |
Homo sapiens | |
| 1.14.13.8 | NADPH | - |
Homo sapiens | |
| 1.14.14.1 | FMN | - |
Homo sapiens | |
| 1.14.14.1 | NADPH | dependent on | Homo sapiens | |
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