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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:03:34 UTC
HMDB IDHMDB00925
Secondary Accession NumbersNone
Metabolite Identification
Common NameTrimethylamine N-oxide
DescriptionTrimethylamine N-oxide (TMAO) is an oxidation product of trimethylamine and a common metabolite in animals and humans. In particular, trimethylamine-N-oxide is biosynthesized endogenously from trimethylamine, which is derived from choline, which can be derived from dietary lecithin (phosphatidylcholines) or dietary carnitine. TMAO decomposes to trimethylamine (TMA), which is the main odorant that is characteristic of degrading seafood. TMAO is an osmolyte that the body will use to counteract the effects of increased concentrations of urea (due to kidney failure) and high levels can be used as a biomarker for kidney problems. Fish odor syndrome or trimethylaminuria is a defect in the production of the enzyme flavin containing monooxygenase 3 (FMO3) causing incomplete breakdown of trimethylamine from choline-containing food into trimethylamine oxide. Trimethylamine then builds up and is released in the person's sweat, urine, and breath, giving off a strong fishy odor. The concentration of TMAO in the blood increases after consuming foods containing carnitine or lecithin (phosphatidylcholines), if the bacteria that convert those substances to TMAO are present in the gut (PMID: 23614584 ). High concentrations of carnitine are found in red meat, some energy drinks, and certain dietary supplements; lecithin is found in eggs and is commonly used as an ingredient in processed food. High levels of TMAO are found in many seafoods. Some types of normal gut bacteria (e.g. species of Acinetobacter) in the human gut convert dietary carnitine and dietary lecithin to TMAO (PMID: 21475195 ). TMAO alters cholesterol metabolism in the intestines, in the liver and in arterial wall. When TMAO is present, cholesterol metabolism is altered and there is an increased deposition of cholesterol within, and decreased removal of cholesterol from, peripheral cells such as those in the artery wall (PMID: 23563705 ).
Structure
Thumb
Synonyms
ValueSource
(CH3)3NOChEBI
Me3n(+)O(-)ChEBI
Me3n(O)ChEBI
N(CH3)3OChEBI
TMAOChEBI
Trimethylamine oxideChEBI
TrimethylaminoxidChEBI
TrimethyloxamineChEBI
N,N-Dimethylmethanamine N-oxideHMDB
TMA-oxideHMDB
Trimethylamine-N-oxideHMDB
TrioxHMDB
Chemical FormulaC3H9NO
Average Molecular Weight75.1097
Monoisotopic Molecular Weight75.068413915
IUPAC NameN,N-dimethylmethanamine oxide
Traditional Nametrimethylamine-n-oxide
CAS Registry Number1184-78-7
SMILES
C[N+](C)(C)[O-]
InChI Identifier
InChI=1S/C3H9NO/c1-4(2,3)5/h1-3H3
InChI KeyInChIKey=UYPYRKYUKCHHIB-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as trisubstituted amine oxides and derivatives. These are amine oxides where the N atom is trisubstituted with three organic groups.
KingdomOrganic compounds
Super ClassOrganonitrogen compounds
ClassAmines
Sub ClassAmine oxides and derivatives
Direct ParentTrisubstituted amine oxides and derivatives
Alternative Parents
Substituents
  • Trisubstituted n-oxide
  • Hydrocarbon derivative
  • Organic salt
  • Organic zwitterion
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Drug metabolite
  • Endogenous
  • Microbial
Biofunction
  • Osmolyte
  • Waste products
ApplicationNot Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point95 - 99 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility454 mg/mLNot Available
LogPNot AvailableNot Available
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
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
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
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
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Blood
  • Feces
  • Saliva
  • Urine
Tissue Location
  • Epidermis
  • Kidney
  • Liver
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified38.81 +/- 20.37 uMAdult (>18 years old)BothNormal details
BloodDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
BloodDetected and Quantified37.8 +/- 20.4 uMAdult (>18 years old)BothNormal details
FecesDetected and Quantified3.30 (2.01–4.59) ppmInfant (0-1 year old)Not Specified
Normal
details
FecesDetected and Quantified4.15 (2.15–6.15) ppmInfant (0-1 year old)Not Specified
Normal
details
FecesDetected and Quantified6.76 (1.73–11.79) ppmInfant (0-1 year old)Not Specified
Normal
details
FecesDetected but not QuantifiedNot ApplicableChildren (1-13 years old)Not Specified
Normal
details
SalivaDetected and Quantified>10 uMAdult (>18 years old)BothNormal details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)MaleNormal details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothNormal details
UrineDetected and Quantified33.70 umol/mmol creatinineAdult (>18 years old)MaleNormal
    • Shaykhutdinov RA,...
details
UrineDetected and Quantified74.4 +/- 76.6 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified67.1 +/- 45.8 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified69.88 +/- 55.003 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected and Quantified91 (4.8-509) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified118.7 (35.5-202.1) umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified99.72 +/- 31.82 uMAdult (>18 years old)Bothuremia details
BloodDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothColorectal cancer details
BloodDetected and Quantified99.9 +/- 31.9 uMAdult (>18 years old)Both
Kidney disease
details
BloodDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Pancreatic
details
FecesDetected but not QuantifiedNot ApplicableChildren (1-13 years old)Not Specified
Treated celiac disease
details
UrineDetected and Quantified54.493 +/- 50.173 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified143 umol/mmol creatinineAdult (>18 years old)FemaleRhabdomyolysis details
UrineDetected and Quantified78 +/- 71 umol/mmol creatinineAdult (>18 years old)BothLung cancer details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothColorectal cancer details
UrineDetected and Quantified15.7 umol/mmol creatinineAdult (>18 years old)MaleTrimethylaminuria details
UrineDetected and Quantified66 +/- 1.3 umol/mmol creatinineAdult (>18 years old)Both3-Hydroxy-3- methylglutaryl-CoA lyase (HL) deficency details
UrineDetected and Quantified74 +/- 2.2 umol/mmol creatinineAdult (>18 years old)Both3-Hydroxy-3- methylglutaryl-CoA lyase (HL) deficency details
UrineDetected and Quantified38.1 +/- 2.9 umol/mmol creatinineAdult (>18 years old)BothArgininosuccinic aciduria (ASL) details
UrineDetected and Quantified2144.7 +/- 123.4 umol/mmol creatinineAdult (>18 years old)BothPropionic acidemia details
UrineDetected and Quantified140.5 +/- 14.1 umol/mmol creatinineAdult (>18 years old)BothPropionic acidemia details
UrineDetected and Quantified36.4 +/- 1.1 umol/mmol creatinineAdult (>18 years old)BothTyrosinemia I details
UrineDetected and Quantified16.1 +/- 1.5 umol/mmol creatinineAdult (>18 years old)BothTyrosinemia I details
UrineDetected and Quantified33.1 +/- 1.9 umol/mmol creatinineAdult (>18 years old)BothMaple syrup urine disease details
Associated Disorders and Diseases
Disease References
Trimethylaminuria
  1. 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. [9246418 ]
Kidney disease
  1. Bain MA, Faull R, Fornasini G, Milne RW, Evans AM: Accumulation of trimethylamine and trimethylamine-N-oxide in end-stage renal disease patients undergoing haemodialysis. Nephrol Dial Transplant. 2006 May;21(5):1300-4. Epub 2006 Jan 9. [16401621 ]
Lung Cancer
  1. Stretch C, Eastman T, Mandal R, Eisner R, Wishart DS, Mourtzakis M, Prado CM, Damaraju S, Ball RO, Greiner R, Baracos VE: Prediction of skeletal muscle and fat mass in patients with advanced cancer using a metabolomic approach. J Nutr. 2012 Jan;142(1):14-21. doi: 10.3945/jn.111.147751. Epub 2011 Dec 7. [22157537 ]
Rhabdomyolysis
  1. Bairaktari E, Seferiadis K, Liamis G, Psihogios N, Tsolas O, Elisaf M: Rhabdomyolysis-related renal tubular damage studied by proton nuclear magnetic resonance spectroscopy of urine. Clin Chem. 2002 Jul;48(7):1106-9. [12089184 ]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDDBMET00513
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB010413
KNApSAcK IDNot Available
Chemspider ID1113
KEGG Compound IDC01104
BioCyc IDTRIMENTHLAMINE-N-O
BiGG IDNot Available
Wikipedia LinkTrimethylamine oxide
NuGOwiki LinkHMDB00925
Metagene LinkHMDB00925
METLIN ID5876
PubChem Compound1145
PDB IDTMO
ChEBI ID15724
References
Synthesis ReferenceHazard, Rene; Cheymol, Jean; Chabrier, Pierre. Trimethylamine oxide. (1962), 1 p.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. 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. [7762816 ]
  2. 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. [8257730 ]
  3. 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. [12097436 ]
  4. 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. [16082628 ]
  5. 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. [9665433 ]
  6. 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. [9246418 ]
  7. 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. [15304308 ]
  8. Thithapandha A: A pharmacogenetic study of trimethylaminuria in Orientals. Pharmacogenetics. 1997 Dec;7(6):497-501. [9429235 ]
  9. On SL, Holmes B: Effect of inoculum size on the phenotypic characterization of Campylobacter species. J Clin Microbiol. 1991 May;29(5):923-6. [2056060 ]
  10. 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. [15784681 ]
  11. 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. [15563884 ]
  12. 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. [16086821 ]
  13. 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. [15641800 ]
  14. 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. [23614584 ]
  15. 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. [21475195 ]
  16. 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. [23563705 ]

Enzymes

General function:
Involved in flavin-containing monooxygenase activity
Specific function:
In contrast with other forms of FMO it does not seem to be a drug-metabolizing enzyme.
Gene Name:
FMO5
Uniprot ID:
P49326
Molecular weight:
32480.04
Reactions
Trimethylamine + NADPH + Hydrogen Ion + Oxygen → Trimethylamine N-oxide + NADP + Waterdetails
General function:
Involved in flavin-containing monooxygenase activity
Specific function:
Catalyzes the N-oxidation of certain primary alkylamines to their oximes via an N-hydroxylamine intermediate. Inactive toward certain tertiary amines, such as imipramine or chloropromazine. Can catalyze the S-oxidation of methimazole. The truncated form is catalytically inactive.
Gene Name:
FMO2
Uniprot ID:
Q99518
Molecular weight:
53643.29
Reactions
Trimethylamine + NADPH + Hydrogen Ion + Oxygen → Trimethylamine N-oxide + NADP + Waterdetails
General function:
Involved in flavin-containing monooxygenase activity
Specific function:
This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides.
Gene Name:
FMO4
Uniprot ID:
P31512
Molecular weight:
63342.055
Reactions
Trimethylamine + NADPH + Hydrogen Ion + Oxygen → Trimethylamine N-oxide + NADP + Waterdetails
General function:
Involved in flavin-containing monooxygenase activity
Specific function:
Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an important role in the metabolism of trimethylamine (TMA), via the production of TMA N-oxide (TMAO). Is also able to perform S-oxidation when acting on sulfide compounds.
Gene Name:
FMO3
Uniprot ID:
P31513
Molecular weight:
60032.975
Reactions
Trimethylamine + NADPH + Oxygen → Trimethylamine N-oxide + NADP + Waterdetails
Trimethylamine + NADPH + Hydrogen Ion + Oxygen → Trimethylamine N-oxide + NADP + Waterdetails
General function:
Involved in flavin-containing monooxygenase activity
Specific function:
This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. Form I catalyzes the N-oxygenation of secondary and tertiary amines.
Gene Name:
FMO1
Uniprot ID:
Q01740
Molecular weight:
60310.285
Reactions
Trimethylamine + NADPH + Hydrogen Ion + Oxygen → Trimethylamine N-oxide + NADP + Waterdetails