Record Information
Version2.0
Creation Date2012-05-31 14:06:52 -0600
Update Date2015-06-03 15:54:48 -0600
Secondary Accession Numbers
  • ECMDB04161
Identification
Name:Trimethylamine N-Oxide
Description:Trimethylamine N-oxide (TMAO) is found at high concentrations in the tissues of fish, and the bacterial reduction of this compound to foul-smelling trimethylamine is a major process in the spoilage of fish. Trimethylamine N-oxide reductase (TOR or TMAO reductase, EC 1.7.2.3) is a microbial enzyme that can reduce TMAO into trimethylamine (TMA), as part of the electron transport chain. The enzyme has been purified from E. coli. It can accept electrons from cytochromes. (Wikipedia; PMID: 1337081; PMID: 11056172)
Structure
Thumb
Synonyms:
  • N,N-Dimethylmethanamine N-oxide
  • TMA-oxide
  • TMAO
  • TMeAla-oxide
  • Trimethylamine N-oxide
  • Trimethylamine oxide
  • Trimethylamine-N-oxide
  • Triox
Chemical Formula:C3H9NO
Weight:Average: 75.1097
Monoisotopic: 75.068413915
InChI Key:UYPYRKYUKCHHIB-UHFFFAOYSA-N
InChI:InChI=1S/C3H9NO/c1-4(2,3)5/h1-3H3
CAS number:1184-78-7
IUPAC Name:N,N-dimethylmethanamine oxide
Traditional IUPAC Name:trimethylamine-n-oxide
SMILES:C[N+](C)(C)[O-]
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as trialkyl amine oxides. These are hydrocarbyl derivatives of the aminoxide anion, with the general formula R3N+[O-] or R3N=O, where R is an alkyl group.
KingdomOrganic compounds
Super ClassOrganic nitrogen compounds
ClassOrganonitrogen compounds
Sub ClassAminoxides
Direct ParentTrialkyl amine oxides
Alternative Parents
Substituents
  • Trialkyl amine oxide
  • Trisubstituted n-oxide
  • N-oxide
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Physical Properties
State:Solid
Charge:0
Melting point:95-99 °C
Experimental Properties:
PropertyValueSource
Water Solubility:454 mg/mL [HMP experimental]PhysProp
Predicted Properties
PropertyValueSource
Water Solubility57.8 mg/mLALOGPS
logP-2ALOGPS
logP-0.93ChemAxon
logS-0.11ALOGPS
pKa (Strongest Basic)4.66ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area26.88 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity22.03 m3·mol-1ChemAxon
Polarizability8.32 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Biological Properties
Cellular Locations:Cytoplasm
Reactions:
SMPDB Pathways:
Collection of Reactions without pathwaysPW001891 Pw001891Pw001891 greyscalePw001891 simple
N-oxide electron transferPW001889 Pw001889Pw001889 greyscalePw001889 simple
KEGG Pathways:
EcoCyc Pathways:
  • NADH to trimethylamine N-oxide electron transfer PWY0-1347
  • formate to trimethylamine N-oxide electron transfer PWY0-1355
Concentrations
Not Available
Spectra
Spectra:
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MSsplash10-06vi-9000000000-426384c1c05ab5b584beView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-056r-9000000000-9ba99fcfab36000c7757View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0a4i-9000000000-77dcb5a2685e3154e9f6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-052f-9000000000-dabc3f78669637484204View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-004i-9000000000-0e637352d88abe7c2b0aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-0a4i-9000000000-d155aab0cf63bd6365caView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-0a4i-9000000000-54c4798b9d38df37e8a2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-0a4i-9000000000-7b4ea1bc9a14eef87f35View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-052f-9000000000-1e5a0675e8b58686f975View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) 30V, Positivesplash10-056r-9000000000-aeb64eb28a53521764cfView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-004i-9000000000-0e637352d88abe7c2b0aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0a4i-9000000000-d155aab0cf63bd6365caView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0a4i-9000000000-54c4798b9d38df37e8a2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0a4i-9000000000-7b4ea1bc9a14eef87f35View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-052f-9000000000-7f27d29305df82f75dfeView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-056r-9000000000-72bdd3a0798c28024038View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-9000000000-ff78646c3e3f75afce16View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-9000000000-ed1a5c9cf14802f3a117View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-056r-9000000000-388e7087787fdbab7a18View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-9000000000-6298f48fa1844aa5f438View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-9000000000-9ca491949ce95689c50cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00di-9000000000-89485046f830076c9234View in MoNA
MSMass Spectrum (Electron Ionization)splash10-056r-9000000000-28a96c1111fa94368c76View in MoNA
1D NMR13C NMR SpectrumNot Available
1D NMR1H NMR SpectrumNot Available
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
References
References:
  • Arata, H., Shimizu, M., Takamiya, K. (1992). "Purification and properties of trimethylamine N-oxide reductase from aerobic photosynthetic bacterium Roseobacter denitrificans." J Biochem 112:470-475. Pubmed: 1337081
  • Chung YL, Rider LG, Bell JD, Summers RM, Zemel LS, Rennebohm RM, Passo MH, Hicks J, Miller FW, Scott DL: Muscle metabolites, detected in urine by proton spectroscopy, correlate with disease damage in juvenile idiopathic inflammatory myopathies. Arthritis Rheum. 2005 Aug 15;53(4):565-70. Pubmed: 16082628
  • Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. Pubmed: 22080510
  • Kenyon S, Carmichael PL, Khalaque S, Panchal S, Waring R, Harris R, Smith RL, Mitchell SC: The passage of trimethylamine across rat and human skin. Food Chem Toxicol. 2004 Oct;42(10):1619-28. Pubmed: 15304308
  • Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. Pubmed: 21097882
  • Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL: Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 May;19(5):576-85. doi: 10.1038/nm.3145. Epub 2013 Apr 7. Pubmed: 23563705
  • Maschke S, Wahl A, Azaroual N, Boulet O, Crunelle V, Imbenotte M, Foulard M, Vermeersch G, Lhermitte M: 1H-NMR analysis of trimethylamine in urine for the diagnosis of fish-odour syndrome. Clin Chim Acta. 1997 Jul 25;263(2):139-46. Pubmed: 9246418
  • Messana I, Forni F, Ferrari F, Rossi C, Giardina B, Zuppi C: Proton nuclear magnetic resonance spectral profiles of urine in type II diabetic patients. Clin Chem. 1998 Jul;44(7):1529-34. Pubmed: 9665433
  • Nicholson JK, Foxall PJ, Spraul M, Farrant RD, Lindon JC: 750 MHz 1H and 1H-13C NMR spectroscopy of human blood plasma. Anal Chem. 1995 Mar 1;67(5):793-811. Pubmed: 7762816
  • On SL, Holmes B: Effect of inoculum size on the phenotypic characterization of Campylobacter species. J Clin Microbiol. 1991 May;29(5):923-6. Pubmed: 2056060
  • Podadera P, Sipahi AM, Areas JA, Lanfer-Marquez UM: Diagnosis of suspected trimethylaminuria by NMR spectroscopy. Clin Chim Acta. 2005 Jan;351(1-2):149-54. Pubmed: 15563884
  • Shepshelovich J, Goldstein-Magal L, Globerson A, Yen PM, Rotman-Pikielny P, Hirschberg K: Protein synthesis inhibitors and the chemical chaperone TMAO reverse endoplasmic reticulum perturbation induced by overexpression of the iodide transporter pendrin. J Cell Sci. 2005 Apr 15;118(Pt 8):1577-86. Epub 2005 Mar 22. Pubmed: 15784681
  • Silwood CJ, Lynch E, Claxson AW, Grootveld MC: 1H and (13)C NMR spectroscopic analysis of human saliva. J Dent Res. 2002 Jun;81(6):422-7. Pubmed: 12097436
  • Sweatman BC, Farrant RD, Holmes E, Ghauri FY, Nicholson JK, Lindon JC: 600 MHz 1H-NMR spectroscopy of human cerebrospinal fluid: effects of sample manipulation and assignment of resonances. J Pharm Biomed Anal. 1993 Aug;11(8):651-64. Pubmed: 8257730
  • Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL: Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013 Apr 25;368(17):1575-84. doi: 10.1056/NEJMoa1109400. Pubmed: 23614584
  • Thithapandha A: A pharmacogenetic study of trimethylaminuria in Orientals. Pharmacogenetics. 1997 Dec;7(6):497-501. Pubmed: 9429235
  • Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL: Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922. Pubmed: 21475195
  • Watt K, Jess TJ, Kelly SM, Price NC, McEwan IJ: Induced alpha-helix structure in the aryl hydrocarbon receptor transactivation domain modulates protein-protein interactions. Biochemistry. 2005 Jan 18;44(2):734-43. Pubmed: 15641800
  • Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. Pubmed: 18331064
  • Wolrath H, Stahlbom B, Hallen A, Forsum U: Trimethylamine and trimethylamine oxide levels in normal women and women with bacterial vaginosis reflect a local metabolism in vaginal secretion as compared to urine. APMIS. 2005 Jul-Aug;113(7-8):513-6. Pubmed: 16086821
Synthesis Reference:Hazard, Rene; Cheymol, Jean; Chabrier, Pierre. Trimethylamine oxide. (1962), 1 p.
Material Safety Data Sheet (MSDS)Not Available
External Links:
ResourceLink
CHEBI ID15724
HMDB IDHMDB00925
Pubchem Compound ID1145
Kegg IDC01104
ChemSpider ID1113
WikipediaTrimethylamine oxide
BioCyc IDTRIMENTHLAMINE-N-O
EcoCyc IDTRIMENTHLAMINE-N-O
Ligand ExpoTMO

Enzymes

General function:
Involved in electron carrier activity
Specific function:
Electron transfer subunit of the terminal reductase during anaerobic growth on various sulfoxide and N-oxide compounds
Gene Name:
ynfG
Uniprot ID:
P0AAJ1
Molecular weight:
22752
General function:
Involved in dimethyl sulfoxide reductase activity
Specific function:
Terminal reductase during anaerobic growth on various sulfoxide and N-oxide compounds. Allows E.coli to grow anaerobically on Me(2)SO as respiratory oxidant
Gene Name:
dmsA
Uniprot ID:
P18775
Molecular weight:
90398
Reactions
Dimethylsulfide + menaquinone + H(2)O = dimethylsulfoxide + menaquinol.
General function:
Involved in electron carrier activity
Specific function:
Electron transfer subunit of the terminal reductase during anaerobic growth on various sulfoxide and N-oxide compounds
Gene Name:
dmsB
Uniprot ID:
P18776
Molecular weight:
22869
General function:
Involved in dimethyl sulfoxide reductase activity
Specific function:
Terminal reductase during anaerobic growth on various sulfoxide and N-oxide compounds
Gene Name:
ynfE
Uniprot ID:
P77374
Molecular weight:
89779
General function:
Involved in dimethyl sulfoxide reductase activity
Specific function:
Terminal reductase during anaerobic growth on various sulfoxide and N-oxide compounds
Gene Name:
ynfF
Uniprot ID:
P77783
Molecular weight:
89986
General function:
Involved in oxidoreductase activity
Specific function:
Reduces trimethylamine-N-oxide (TMAO) into trimethylamine; an anaerobic reaction coupled to energy-yielding reactions. Can also reduce other N- and S-oxide compounds such as 4-methylmorpholine-N-oxide and biotin sulfoxide (BSO), but with a lower catalytic efficiency
Gene Name:
torZ
Uniprot ID:
P46923
Molecular weight:
88964
Reactions
Trimethylamine + 2 (ferricytochrome c)-subunit + H(2)O = trimethylamine N-oxide + 2 (ferrocytochrome c)-subunit + 2 H(+).
General function:
Involved in iron ion binding
Specific function:
Part of the anaerobic respiratory chain of trimethylamine-N-oxide reductase torZ. Required for electron transfer to the torZ terminal enzyme
Gene Name:
torY
Uniprot ID:
P52005
Molecular weight:
40286
General function:
Involved in anaerobic electron transport chain
Specific function:
Terminal reductase during anaerobic growth on various sulfoxide and N-oxide compounds. DmsC anchors the dmsAB dimer to the membrane and stabilizes it
Gene Name:
dmsC
Uniprot ID:
P18777
Molecular weight:
30826
General function:
Involved in oxidoreductase activity
Specific function:
Reduces trimethylamine-N-oxide (TMAO) into trimethylamine; an anaerobic reaction coupled to energy-yielding reactions
Gene Name:
torA
Uniprot ID:
P33225
Molecular weight:
94455
Reactions
Trimethylamine + 2 (ferricytochrome c)-subunit + H(2)O = trimethylamine N-oxide + 2 (ferrocytochrome c)-subunit + 2 H(+).
General function:
Involved in iron ion binding
Specific function:
Part of the anaerobic respiratory chain of trimethylamine-N-oxide reductase torA. Acts by transferring electrons from the membranous menaquinones to torA. This transfer probably involves an electron transfer pathway from menaquinones to the N-terminal domain of torC, then from the N-terminus to the C-terminus, and finally to torA. TorC apocytochrome negatively autoregulates the torCAD operon probably by inhibiting the torS kinase activity
Gene Name:
torC
Uniprot ID:
P33226
Molecular weight:
43606
General function:
Involved in anaerobic electron transport chain
Specific function:
Terminal reductase during anaerobic growth on various sulfoxide and N-oxide compounds. The C subunit anchors the other two subunits to the membrane and stabilize the catalytic subunits
Gene Name:
ynfH
Uniprot ID:
P76173
Molecular weight:
30523

Transporters

General function:
Involved in transporter activity
Specific function:
Non-specific porin
Gene Name:
ompN
Uniprot ID:
P77747
Molecular weight:
41220
General function:
Involved in transporter activity
Specific function:
Uptake of inorganic phosphate, phosphorylated compounds, and some other negatively charged solutes
Gene Name:
phoE
Uniprot ID:
P02932
Molecular weight:
38922
General function:
Involved in transporter activity
Specific function:
OmpF is a porin that forms passive diffusion pores which allow small molecular weight hydrophilic materials across the outer membrane. It is also a receptor for the bacteriophage T2
Gene Name:
ompF
Uniprot ID:
P02931
Molecular weight:
39333
General function:
Involved in transporter activity
Specific function:
Forms passive diffusion pores which allow small molecular weight hydrophilic materials across the outer membrane
Gene Name:
ompC
Uniprot ID:
P06996
Molecular weight:
40368