KEGG   ENZYME: 1.14.13.148Help
Entry
EC 1.14.13.148              Enzyme                                 

Name
trimethylamine monooxygenase;
flavin-containing monooxygenase 3;
FMO3;
tmm (gene name)
Class
Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor
BRITE hierarchy
Sysname
N,N,N-trimethylamine,NADPH:oxygen oxidoreductase (N-oxide-forming)
Reaction(IUBMB)
N,N,N-trimethylamine + NADPH + H+ + O2 = N,N,N-trimethylamine N-oxide + NADP+ + H2O [RN:R05623]
Reaction(KEGG)
Substrate
N,N,N-trimethylamine;
NADPH [CPD:C00005];
H+ [CPD:C00080];
O2 [CPD:C00007]
Product
N,N,N-trimethylamine N-oxide;
NADP+ [CPD:C00006];
H2O [CPD:C00001]
Comment
A flavoprotein. The bacterial enzyme enables bacteria to use trimethylamine as the sole source of carbon and energy [1,4]. The mammalian enzyme is involved in detoxification of trimethylamine. Mutations in the human enzyme cause the inheritable disease known as trimethylaminuria (fish odor syndrome) [2,3].
History
EC 1.14.13.148 created 2012
Pathway
ec00680  Methane metabolism
Orthology
K18277  trimethylamine monooxygenase
Genes
STEK: AXG53_01325
PMY: Pmen_3459
PRE: PCA10_14390
PCQ: PcP3B5_34340(hapE_3)
PPG: PputGB1_2270
PPUT: L483_19090
PPUN: PP4_21860
PFS: PFLU_2331
PFE: PSF113_3540
PMAN: OU5_0413
PSET: THL1_1501
PSIL: PMA3_11125
PHA: PSHAa1699
PTN: PTRA_a2101(tmm)
PNG: PNIG_a2218(tmm)
OCE: GU3_01635
BAV: BAV1821
BTRM: SAMEA390648701700(hapE_2)
HAR: HEAR2456
LCH: Lcho_0154
MXA: MXAN_0506
MLO: mlr7328
AMIH: CO731_04990(hapE_2)
SME: SMc04149
SMER: DU99_00555
SMD: Smed_3315
ARA: Arad_8377
RLE: pRL110548
RLG: Rleg_6584
AZC: AZC_1374
MSL: Msil_3604
SIL: SPO1551(tmm)
RDE: RD1_0632
PAMN: pAMV1p0112(tmm)
CID: P73_0139
SSAN: NX02_15600
GXL: H845_65
MVA: Mvan_1201
MGI: Mflv_5135
MPHL: MPHLCCUG_02553(pamO_2)
MVQ: MYVA_1579
CGL: NCgl1096(Cgl1141)
CGB: cg1292
CGU: WA5_1096
CGT: cgR_1225
CGM: cgp_1292
CGJ: AR0_06205
CEF: CE1213
REQ: REQ_34750
RRT: 4535765_01758(hapE_3)
ARM: ART_3120
NAL: B005_2927
TER: Tery_0516
SMIZ: 4412673_01531(hapE)
MPW: MPR_3295
 » show all
Taxonomy
Reference
1  [PMID:4404764]
  Authors
Large PJ, Boulton CA, Crabbe MJ
  Title
The reduced nicotinamide-adenine dinucleotide phosphate- and oxygen-dependent N-oxygenation of trimethylamine by Pseudomonas aminovorans.
  Journal
Biochem J 128:137P-138P (1972)
Reference
2  [PMID:9417913]
  Authors
Dolphin CT, Riley JH, Smith RL, Shephard EA, Phillips IR
  Title
Structural organization of the human flavin-containing monooxygenase 3 gene (FMO3), the favored candidate for fish-odor syndrome, determined directly from genomic DNA.
  Journal
Genomics 46:260-7 (1997)
DOI:10.1006/geno.1997.5031
  Sequence
[hsa:2328]
Reference
3  [PMID:9536088]
  Authors
Treacy EP, Akerman BR, Chow LM, Youil R, Bibeau C, Lin J, Bruce AG, Knight M, Danks DM, Cashman JR, Forrest SM
  Title
Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication.
  Journal
Hum Mol Genet 7:839-45 (1998)
DOI:10.1093/hmg/7.5.839
  Sequence
[rno:84493]
Reference
4  [PMID:22006322]
  Authors
Chen Y, Patel NA, Crombie A, Scrivens JH, Murrell JC
  Title
Bacterial flavin-containing monooxygenase is trimethylamine monooxygenase.
  Journal
Proc Natl Acad Sci U S A 108:17791-6 (2011)
DOI:10.1073/pnas.1112928108
  Sequence
[msl:Msil_3604]
Other DBs
ExplorEnz - The Enzyme Database: 1.14.13.148
IUBMB Enzyme Nomenclature: 1.14.13.148
ExPASy - ENZYME nomenclature database: 1.14.13.148
BRENDA, the Enzyme Database: 1.14.13.148

KEGG   ENZYME: 1.14.13.8Help
Entry
EC 1.14.13.8                Enzyme                                 

Name
flavin-containing monooxygenase;
dimethylaniline oxidase;
dimethylaniline N-oxidase;
FAD-containing monooxygenase;
N,N-dimethylaniline monooxygenase;
DMA oxidase;
flavin mixed function oxidase;
Ziegler's enzyme;
mixed-function amine oxidase;
FMO;
FMO-I;
FMO-II;
FMO1;
FMO2;
FMO3;
FMO4;
FMO5;
flavin monooxygenase;
methylphenyltetrahydropyridine N-monooxygenase;
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine:oxygen N-oxidoreductase;
dimethylaniline monooxygenase (N-oxide-forming)
Class
Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor
BRITE hierarchy
Sysname
N,N-dimethylaniline,NADPH:oxygen oxidoreductase (N-oxide-forming)
Reaction(IUBMB)
N,N-dimethylaniline + NADPH + H+ + O2 = N,N-dimethylaniline N-oxide + NADP+ + H2O [RN:R03344]
Reaction(KEGG)
R03344;
(other) R04523 R08266
Show
Substrate
N,N-dimethylaniline [CPD:C02846];
NADPH [CPD:C00005];
H+ [CPD:C00080];
O2 [CPD:C00007]
Product
N,N-dimethylaniline N-oxide [CPD:C01183];
NADP+ [CPD:C00006];
H2O [CPD:C00001]
Comment
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]
History
EC 1.14.13.8 created 1972 (EC 1.13.12.11 created 1992, part-incorporated 2006), modified 2006
Pathway
ec00982  Drug metabolism - cytochrome P450
ec01120  Microbial metabolism in diverse environments
Orthology
K00485  dimethylaniline monooxygenase (N-oxide forming)
Genes
HSA: 2326(FMO1) 2327(FMO2) 2328(FMO3) 2329(FMO4) 2330(FMO5)
PTR: 449587(FMO2) 456443(FMO4) 456444(FMO1) 457505(FMO3) 469472(FMO5) 469566 469579
PPS: 100968405 100971957(FMO5) 100990554(FMO3) 100990887 100991547(FMO2) 100992347(FMO1) 100992930(FMO4)
GGO: 101125254(FMO3) 101126354(FMO2) 101127061(FMO1) 101127553(FMO5) 101127670(FMO4) 101128983 101129103
PON: 100171678(FMO3) 100171693(FMO2) 100173722(FMO1) 100174599(FMO4) 100437586(FMO5) 103890796
NLE: 100589006(FMO3) 100589800(FMO2) 100590364(FMO1) 100591163(FMO4) 100597798(FMO5) 100605282
MCC: 574244(FMO3) 703639(FMO2) 703743(FMO1) 704074(FMO4) 706438(FMO6) 709691(FMO5)
MCF: 101866762(FMO5) 101925939(FMO2) 102121796(FMO3) 102122444(FMO6) 102123829(FMO1) 102124485(FMO4)
CSAB: 103230592(FMO4) 103230596(FMO1) 103230597(FMO2) 103230598 103230599(FMO3) 103247237(FMO5)
RRO: 104668545(FMO4) 104668546(FMO1) 104668547(FMO2) 104668548 104668549(FMO3) 104678671(FMO5)
CJC: 100406306(FMO5) 100408861(FMO4) 100409221(FMO1) 100409812(FMO2) 100410172(FMO3)
SBQ: 101028797 101042140(FMO4) 101042453(FMO1) 101042967(FMO2) 101043515(FMO3) 101044378(FMO5)
MMU: 14261(Fmo1) 14262(Fmo3) 14263(Fmo5) 226564(Fmo4) 226565(Fmo6) 226601(Gm4846) 226604(Gm4847) 240894(Fmo9) 55990(Fmo2)
RNO: 246245(Fmo2) 246247(Fmo4) 246248(Fmo5) 25256(Fmo1) 289193(Fmo13) 304922(Fmo6) 685351 685365(Fmo9) 84493(Fmo3)
HGL: 101707236(Fmo4) 101708672 101709396(Fmo1) 101710590(Fmo2) 101711325(Fmo3) 101713566 101720451(Fmo5)
CFA: 403603(FMO3) 403604(FMO1) 475819(FMO5) 478994 480076(FMO2) 490345(FMO4) 490346
AML: 100476266(FMO5) 100479303 100480885(FMO4) 100481133(FMO1) 100481383(FMO2) 100481633 100481882(FMO3)
FCA: 101086441 101086867(FMO2) 101087122(FMO1) 101089484(FMO3) 101089734(FMO4) 101092533(FMO5)
PTG: 102951929 102967065(FMO5) 102968491 102968984(FMO2) 102969866(FMO1) 102970152(FMO4) 102971622(FMO3)
AJU: 106965588 106966195(FMO4) 106966196(FMO1) 106966197(FMO2) 106966198 106966227(FMO3) 106985833(FMO5)
BTA: 100140223 281167(FMO3) 504401(FMO2) 508781(FMO1) 517828 539356(FMO4) 788719(FMO5)
BOM: 102264945 102275445(FMO3) 102275664(FMO5) 102275918 102276201(FMO2) 102276494(FMO1) 102276938(FMO4)
PHD: 102321365 102321387(FMO3) 102322213 102324687(FMO4) 102325051(FMO1) 102325639(FMO2) 102340761(FMO5)
OAS: 101104165(FMO3) 101104591 101104842(FMO2) 101105089(FMO1) 101105344(FMO4) 101109936 101113713(FMO5)
SSC: 100151788 100152950(FMO5) 100523562(FMO3) 100523745 100525884(FMO2) 100621718(FMO4) 397132(FMO1)
CFR: 102507943 102520326(FMO2) 102520727(FMO1) 102521121(FMO4) 102522247(FMO5) 102522674 102522935(FMO3)
CDK: 105092755(FMO3) 105092757 105092758(FMO2) 105092759(FMO1) 105092760(FMO4) 105092788 105094318(FMO5)
BACU: 103010111 103010326 103015497(FMO3) 103015980(FMO2) 103016262(FMO1) 103016533(FMO4) 103020235(FMO5)
LVE: 103074331(FMO3) 103074606(FMO1) 103074887(FMO4) 103078477(FMO2) 103089199 103091362(FMO5)
ECB: 100052022(FMO3) 100052080(FMO4) 100059647(FMO2) 100059719(FMO1) 100060824 100065455(FMO5)
EAI: 106833813(FMO3) 106833815(FMO2) 106833816(FMO1) 106833817(FMO4) 106847662(FMO5)
MYB: 102252019(FMO5) 102255895 102256395(FMO2) 102256699(FMO1)
MYD: 102751999(FMO5) 102755753(FMO3) 102756035(FMO2) 102756302(FMO1)
RSS: 109436015 109439642(FMO5) 109439758 109453944(FMO3) 109454578(FMO2) 109455612(FMO1) 109456251(FMO4)
PALE: 102884478(FMO4) 102884727(FMO1) 102884985(FMO3) 102885412(FMO2) 102893106(FMO5) 102897341
GGA: 100857694(FMO5) 100857724(DM5L) 395267(FMO3)
APLA: 101791690 101799765(FMO3) 101800205(FMO4) 101804116(FMO5)
TGU: 100222819(FMO1) 100225686(FMO4) 100229443
CMY: 102929468 102929691(FMO3) 102929904(FMO1) 102931687 102936211(FMO2) 102936435(FMO4) 102938406(FMO5)
DRE: 557628(si:dkey-239i20.4) 794311(fmo5)
DME: Dmel_CG3006(Fmo-1)
FCD: 110843767
CEL: CELE_F53F4.5(fmo-4) CELE_H24K24.5(fmo-5) CELE_K08C7.2(fmo-1) CELE_K08C7.5(fmo-2) CELE_Y39A1A.19(fmo-3)
CBR: CBG04445(Cbr-fmo-2) CBG11527(Cbr-fmo-4) CBG18329(Cbr-fmo-3)
TSP: Tsp_08526
OBI: 106875875
HMG: 100201422
ATH: AT1G19250(FMO1) AT5G45180
ALY: ARALYDRAFT_312863(FMO1)
THJ: 104809046
LJA: Lj1g3v3330000.1(Lj1g3v3330000.1) Lj4g3v2215030.1(Lj4g3v2215030.1) Lj6g3v1162950.1(Lj6g3v1162950.1)
DOSA: Os03t0182000-00(Os03g0182000) Os04t0223500-01(Os04g0223500) Os04t0223901-00(Os04g0223901) Os06t0203200-01(Os06g0203200) Os06t0203400-00(Os06g0203400) Os09t0548400-01(Os09g0548400) Os09t0548700-01(Os09g0548700) Os09t0549300-00(Os09g0549300)
ATS: 109734060(LOC109734060) 109734066(LOC109734066) 109738317(LOC109738317) 109742912(LOC109742912) 109751035(LOC109751035) 109774790(LOC109774790) 109774817(LOC109774817) 109774818(LOC109774818) 109774820(LOC109774820) 109774830(LOC109774830) 109779581(LOC109779581) 109779582(LOC109779582) 109779583(LOC109779583) 109779585(LOC109779585) 109779586(LOC109779586) 109782061(LOC109782061) 109783416(LOC109783416) 109785629(LOC109785629)
MGR: MGG_05942
SSCK: SPSK_09027
MBE: MBM_06716
PTE: PTT_15510
SMIN: v1.2.012115.t1(symbB.v1.2.012115.t1) v1.2.019830.t1(symbB.v1.2.019830.t1) v1.2.020877.t1(symbB.v1.2.020877.t1) v1.2.035653.t1(symbB.v1.2.035653.t1)
MVS: MVIS_2965
TMO: TMO_c0822
PNL: PNK_1803
 » show all
Taxonomy
Reference
1  [PMID:4381353]
  Authors
Ziegler DM, Pettit FH.
  Title
Microsomal oxidases. I. The isolation and dialkylarylamine oxygenase activity of pork liver microsomes.
  Journal
Biochemistry 5:2932-8 (1966)
Reference
2  [PMID:3262153]
  Authors
Chiba K, Kubota E, Miyakawa T, Kato Y, Ishizaki T.
  Title
Characterization of hepatic microsomal metabolism as an in vivo detoxication pathway of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice.
  Journal
J Pharmacol Exp Ther 246:1108-15 (1988)
Reference
3
  Authors
Cashman, J.R.
  Title
Structural and catalytic properties of the mammalian flavin-containing monooxygenase.
  Journal
Chem Res Toxicol 8:165-181 (1995)
Reference
4  [PMID:16402899]
  Authors
Cashman JR, Zhang J.
  Title
Human flavin-containing monooxygenases.
  Journal
Annu Rev Pharmacol Toxicol 46:65-100 (2006)
DOI:10.1146/annurev.pharmtox.46.120604.141043
Reference
5  [PMID:3949735]
  Authors
Jones KC, Ballou DP.
  Title
Reactions of the 4a-hydroperoxide of liver microsomal flavin-containing monooxygenase with nucleophilic and electrophilic substrates.
  Journal
J Biol Chem 261:2553-9 (1986)
Reference
6  [PMID:7672012]
  Authors
Chiba K, Kobayashi K, Itoh K, Itoh S, Chiba T, Ishizaki T, Kamataki T.
  Title
N-oxygenation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by the rat liver flavin-containing monooxygenase expressed in yeast cells.
  Journal
Eur J Pharmacol 293:97-100 (1995)
Other DBs
ExplorEnz - The Enzyme Database: 1.14.13.8
IUBMB Enzyme Nomenclature: 1.14.13.8
ExPASy - ENZYME nomenclature database: 1.14.13.8
BRENDA, the Enzyme Database: 1.14.13.8
CAS: 37256-73-8

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