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Human Metabolome Database Version 3.5

Showing metabocard for Trimethylamine N-oxide (HMDB00925)

• Identification
• Taxonomy
• Ontology
• Physical properties
• Spectra
• Biological properties
• Concentrations
• Links
• References

• Blood
• Urine

Record Information
Version	3.5
Creation Date	2005-11-16 08:48:42 -0700
Update Date	2013-02-08 17:09:36 -0700
HMDB ID	HMDB00925
Secondary Accession Numbers	None
Metabolite Identification
Common Name	Trimethylamine N-oxide
Description	Trimethylamine N-oxide (TMAO) is an oxidation product of trimethylamine and a common metabolite in animals and humans. In particular, trimethylamine-N-oxide is biosynthesized from trimethylamine, which is derived from choline. 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 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.
Structure	Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure
Synonyms	N,N-Dimethylmethanamine N-oxide TMA-oxide TMAO Trimethylamine oxide Trimethylamine-N-oxide Triox
Chemical Formula	C3H9NO
Average Molecular Weight	75.1097
Monoisotopic Molecular Weight	75.068413915
IUPAC Name	N,N-dimethylmethanamine oxide
Traditional IUPAC Name	trimethylamine N-oxide
CAS Registry Number	1184-78-7
SMILES	C[N+](C)(C)[O-]
InChI Identifier	InChI=1S/C3H9NO/c1-4(2,3)5/h1-3H3
InChI Key	UYPYRKYUKCHHIB-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom	Organic Compounds
Super Class	Aliphatic Acyclic Compounds
Class	Organic Oxoazanium Compounds
Sub Class	N/A
Other Descriptors	N-oxide(ChEBI) a small molecule(Cyc)
Substituents	N Oxide
Direct Parent	Organic Oxoazanium Compounds
Ontology
Status	Detected and Quantified
Origin	Endogenous Microbial
Biofunction	Osmolyte
Application	Not Available
Cellular locations	Cytoplasm (predicted from logP)
Physical Properties
State	Solid
Experimental Properties	Property Value Reference Melting Point 95 - 99 °C Not Available Boiling Point Not Available Not Available Water Solubility 454 mg/mL Not Available LogP Not Available Not Available
Predicted Properties	Property Value Source LogP -2.01 ALOGPS LogP -0.93 ChemAxon LogS -0.11 ALOGPS pKa (strongest basic) 4.66 ChemAxon Hydrogen Acceptor Count 1 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 26.88 A2 ChemAxon Rotatable Bond Count 0 ChemAxon Refractivity 22.03 ChemAxon Polarizability 8.32 ChemAxon Formal Charge 0 ChemAxon Physiological Charge 0 ChemAxon
Spectra
	13C NMR Spectrum 1H NMR Spectrum MS/MS Spectrum Quattro_QQQ 10 MS/MS Spectrum Quattro_QQQ 25 MS/MS Spectrum Quattro_QQQ 40 MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 10 MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 20 MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 30 MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 40 MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 50 MS/MS Spectrum LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) 30 [1H,13C] 2D NMR Spectrum
Biological Properties
Cellular Locations	Cytoplasm (predicted from logP)
Biofluid Locations	Blood Saliva Urine
Tissue Location	Epidermis
Pathways	Not Available
Normal Concentrations
	Biofluid Status Value Age Sex Condition Comments Blood Detected and Quantified 37.8 +/- 20.4 uM Adult (>18 years old) Both Normal Not Available Saliva Detected and Quantified >10 uM Adult (>18 years old) Both Normal Not Available Urine Detected and not Quantified Not Applicable Adult (>18 years old) Male Normal Not Available Urine Detected and not Quantified Not Applicable Adult (>18 years old) Both Normal Not Available Urine Detected and Quantified 33.70 umol/mmol creatinine Adult (>18 years old) Male Normal Not Available Urine Detected and Quantified 74.4 +/- 76.6 umol/mmol creatinine Adult (>18 years old) Male Normal Not Available Urine Detected and Quantified 67.1 +/- 45.8 umol/mmol creatinine Adult (>18 years old) Female Normal Not Available Urine Detected and Quantified 0.0012 - 0.0087 umol/mmol creatinine Adult (>18 years old) Both Normal Not Available Urine Detected and Quantified 91 (4.8-509) umol/mmol creatinine Adult (>18 years old) Both Normal urine by NMR Urine Detected and Quantified 118.7 (35.5-202.1) umol/mmol creatinine Adult (>18 years old) Both Normal Not Available
Abnormal Concentrations
	Biofluid Status Value Age Sex Condition Comments Blood Detected and Quantified 99.9 +/- 31.9 uM Adult (>18 years old) Both Kidney disease Patients with end-stage renal disease (ESRD) Urine Detected and Quantified 0.001 - 0.0195 umol/mmol creatinine Adult (>18 years old) Both ADPKD Not Available Urine Detected and Quantified 143 umol/mmol creatinine Adult (>18 years old) Female Rhabdomyolysis Not Available Urine Detected and Quantified 78 +/- 71 umol/mmol creatinine Adult (>18 years old) Both Lung cancer Not Available Urine Detected and Quantified 15.7 umol/mmol creatinine Adult (>18 years old) Male Trimethylaminuria Not Available Urine Detected and Quantified 66 +/- 1.3 umol/mmol creatinine Adult (>18 years old) Both 3-Hydroxy-3- methylglutaryl-CoA lyase (HL) deficency Not Available Urine Detected and Quantified 74 +/- 2.2 umol/mmol creatinine Adult (>18 years old) Both 3-Hydroxy-3- methylglutaryl-CoA lyase (HL) deficency Not Available Urine Detected and Quantified 38.1 +/- 2.9 umol/mmol creatinine Adult (>18 years old) Both Arginosuccinic aciduria Not Available Urine Detected and Quantified 2144.7 +/- 123.4 umol/mmol creatinine Adult (>18 years old) Both Propionic acidemia Not Available Urine Detected and Quantified 140.5 +/- 14.1 umol/mmol creatinine Adult (>18 years old) Both Propionic acidemia Not Available Urine Detected and Quantified 36.4 +/- 1.1 umol/mmol creatinine Adult (>18 years old) Both Tyrosinemia I Not Available Urine Detected and Quantified 16.1 +/- 1.5 umol/mmol creatinine Adult (>18 years old) Both Tyrosinemia I Not Available Urine Detected and Quantified 33.1 +/- 1.9 umol/mmol creatinine Adult (>18 years old) Both Maple syrup urine disease Not Available
Associated Disorders and Diseases
Disease References	Trimethylaminuria 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 Lung Cancer Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B, Hau DD, Psychogios N, Dong E, Bouatra S, Mandal R, Sinelnikov I, Xia J, Jia L, Cruz JA, Lim E, Sobsey CA, Shrivastava S, Huang P, Liu P, Fang L, Peng J, Fradette R, Cheng D, Tzur D, Clements M, Lewis A, De Souza A, Zuniga A, Dawe M, Xiong Y, Clive D, Greiner R, Nazyrova A, Shaykhutdinov R, Li L, Vogel HJ, Forsythe I: HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res. 2008 Oct 25. Pubmed: 18953024 Kidney disease 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. Pubmed: 16401621 Rhabdomyolysis 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. Pubmed: 12089184
Associated OMIM IDs	602079 (Trimethylaminuria) 211980 (Lung Cancer)
External Links
DrugBank ID	Not Available
Phenol Explorer Compound ID	Not Available
Phenol Explorer Metabolite ID	Not Available
FoodDB ID	FDB010413
KNApSAcK ID	Not Available
Chemspider ID	1113
KEGG Compound ID	C01104
BioCyc ID	TRIMENTHLAMINE-N-O
BiGG ID	Not Available
Wikipedia Link	Trimethylamine oxide
NuGOwiki Link	HMDB00925
Metagene Link	HMDB00925
METLIN ID	5876
PubChem Compound	1145
PDB ID	TMO
ChEBI ID	15724
References
Synthesis Reference	Hazard, Rene; Cheymol, Jean; Chabrier, Pierre. Trimethylamine oxide. (1962), 1 p.
Material Safety Data Sheet (MSDS)	Not Available
General References	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 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 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 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 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 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 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 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 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 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 Thithapandha A: A pharmacogenetic study of trimethylaminuria in Orientals. Pharmacogenetics. 1997 Dec;7(6):497-501. Pubmed: 9429235 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 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

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