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Revision as of 12:24, 15 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{chembox}} taken from revid 474000857 of page Trimethylamine_N-oxide for the Chem/Drugbox validation project (updated: '').		Latest revision as of 00:26, 14 December 2024 edit Arent (talk | contribs)371 editsNo edit summary
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			{{DISPLAYTITLE:Trimethylamine ''N''-oxide}}{{Cs1 config|name-list-style=vanc|display-authors=6}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|chembox}}) taken from revid of page ] with values updated to verified values.}}
	{{chembox		{{Chembox
			|Watchedfields = changed
	| Name=Trimethylamine ''N''-oxide
			|Name =Trimethylamine ''N''-oxide
	| verifiedrevid = 470615425
			|verifiedrevid = 476993809
	| ImageFile_Ref = {{chemboximage|correct|??}}
			|ImageFile_Ref = {{chemboximage|correct|??}}
	| ImageFile=Trimethylaminoxid.svg
			|ImageFile = Trimethylaminoxid.svg
	|ImageSize= 150
			|ImageSize = 150
	|PIN= ''N'',''N''-dimethylmethanamine oxide
			|ImageAlt = Structural formula
	|IUPACName= trimethylamine oxide
			|ImageFile1 = Trimethylamine-N-oxide-3D-balls.png
	|OtherNames= trimethylamine oxide, TMAO, TMANO
			|ImageSize1 = 150
			|ImageAlt1 = Ball-and-stick model
			|PIN = ''N'',''N''-Dimethylmethanamine ''N''-oxide
			|OtherNames = Trimethylamine oxide, TMAO, TMANO
	|Section1={{Chembox Identifiers		|Section1={{Chembox Identifiers
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 1113		|ChemSpiderID = 1113
	| UNII_Ref = {{fdacite|correct|FDA}}		|UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = FLD0K1SJ1A		|UNII = FLD0K1SJ1A
	| KEGG_Ref = {{keggcite|correct|kegg}}		|UNII1_Ref = {{fdacite|correct|FDA}}
	| KEGG = C01104		|UNII1 = C73WZ0186W
			|UNII1_Comment = (''dihydrate'')
	| InChI = 1/C3H9NO/c1-4(2,3)5/h1-3H3
			|KEGG_Ref = {{keggcite|correct|kegg}}
	| InChIKey = UYPYRKYUKCHHIB-UHFFFAOYAU
			|KEGG = C01104
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C3H9NO/c1-4(2,3)5/h1-3H3		|InChI = 1/C3H9NO/c1-4(2,3)5/h1-3H3
			|InChIKey = UYPYRKYUKCHHIB-UHFFFAOYAU
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
			|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = UYPYRKYUKCHHIB-UHFFFAOYSA-N
			|StdInChI = 1S/C3H9NO/c1-4(2,3)5/h1-3H3
	| CASNo_Ref = {{cascite|correct|CAS}}
			|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| CASNo= 1184-78-7
			|StdInChIKey = UYPYRKYUKCHHIB-UHFFFAOYSA-N
	| PubChem= 1145
	| ChEBI_Ref = {{ebicite|correct|EBI}}		|CASNo_Ref = {{cascite|correct|CAS}}
	| ChEBI = 15724		|CASNo = 1184-78-7
			|CASNo1 = 62637-93-8
	| SMILES = C(C)(C)
			|CASNo1_Comment = (''dihydrate'')
			|PubChem = 1145
			|ChEBI_Ref = {{ebicite|correct|EBI}}
			|ChEBI = 15724
			|SMILES = C(C)(C)
	}}		}}
	|Section2={{Chembox Properties		|Section2={{Chembox Properties
	| C=3 | H = 9 | N = 1 | O = 1		|C=3 | H=9 | N=1 | O=1
	| MolarMass=75.11		|MolarMass =75.11
	| Appearance= colourless solid		|Appearance = colorless solid
			|MeltingPtC = 220 to 222
	| Density=
	| MeltingPt= 220–222 °C (hydrate: 96 °C)		|MeltingPt_notes = (dihydrate: 96 °C)
			|Solubility = good
	| BoilingPt=
			|Dipole = 5.4 ]
	| Solubility= good
	}}
	}}		}}
			}}
			'''Trimethylamine ''N''-oxide''' ('''TMAO''') is an ] with the formula (CH<sub>3</sub>)<sub>3</sub>NO. It is in the class of ]s. Although the anhydrous compound is known, trimethylamine ''N''-oxide is usually encountered as the ]. Both the anhydrous and hydrated materials are white, water-soluble solids.
			TMAO is found in the tissues of marine crustaceans and marine fish, where it prevents water pressure from ] and thus killing the animal. The concentration of TMAO increases with the depth at which the animal lives; TMAO is found in high concentrations in the deepest-living described fish species, '']'', which was found in the ], at a recorded depth of {{convert|8076|m|ft|abbr=on}}.<ref name=Linley2016>{{cite journal|author1=Linley, T.D.|author2=M.E. Gerringer|author3=P.H. Yancey|author4=J.C. Drazen|author5=C.L. Weinstock|author6=A.J. Jamieson|year=2016|title=Fishes of the hadal zone including new species, in situ observations and depth records of Liparidae|journal=Deep Sea Research Part I: Oceanographic Research Papers|volume=114|pages=99–110|doi=10.1016/j.dsr.2016.05.003|bibcode=2016DSRI..114...99L|doi-access=free}}</ref><ref name=Gerringer2017>{{cite journal|author1=Gerringer, M.E.|author2=T.D. Linley|author3=P.H. Yancey|author4=A.J. Jamieson|author5=E. Goetze|author6=J.C. Drazen|year=2016|title=Pseudoliparis swirei sp. nov.: A newly-discovered hadal snailfish (Scorpaeniformes: Liparidae) from the Mariana Trench|journal=Zootaxa|volume=4358|issue=1|pages=161–177|doi=10.11646/zootaxa.4358.1.7|pmid=29245485|doi-access=free}}</ref>
			In animals, TMAO is a product of the oxidation of ], a common ] of trimethyl quaternary ammonium compounds, like ], ], and ].<ref>{{cite journal |author1=Baker, J.R. |author2=Chaykin, S. |title= The biosynthesis of trimethylamine-''N''-oxide |journal= ] |date=1 April 1962 |volume= 237 |pages= 1309–13 |url= http://www.jbc.org/cgi/content/citation/237/4/1309 |pmid= 13864146 |issue= 4|doi=10.1016/S0021-9258(18)60325-4 |doi-access= free }}</ref> High TMAO concentrations are associated with an increased risk of all-cause mortality and cardiovascular disease.<ref name="Schiattarella">{{cite journal|year=2017|author=Schiattarella GG, Sannino A, Toscano E, Giugliano G, Gargiulo G, Franzone A, Trimarco B, Esposito G, Perrino C.|title=Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: a systematic review and dose-response meta-analysis|journal=European Heart Journal|url=|volume=38|issue=39|pages=2948–2956|doi=10.1093/eurheartj/ehx342|pmid=29020409|doi-access=free}}</ref><ref>{{cite journal|author=Li D, Lu Y, Yuan S, Cai X, He Y, Chen J, Wu Q, He D, Fang A, Bo Y, Song P, Bogaert D, Tsilidis K, Larsson SC, Yu H, Zhu H, Theodoratou E, Zhu Y, Li X. |year=2022|title=Gut microbiota-derived metabolite trimethylamine-N-oxide and multiple health outcomes: an umbrella review and updated meta-analysis|journal=Am J Clin Nutr|volume=116|issue=1|pages=230–243|doi=10.1093/ajcn/nqac074|pmid=35348578|pmc=9257469 }}</ref><ref>{{cite journal|author=Dean YE, Rouzan SS, Loayza Pintado JJ, Talat NE, Mohamed ARH, Verma S, Anwar Kamdi Z, Gir D, Helmy A, Helmy Z, Afzal A, Mady T, Hazimeh Y, Aiash H.|year=2023|title=Serum trimethylamine N-oxide levels among coronary artery disease and acute coronary syndrome patients: a systematic review and meta-analysis|journal=Annals of Medicine and Surgery|volume=85|issue=12|pages=6123–6133|doi=10.1097/MS9.0000000000001426|pmid=38098555|pmc=10718322}}</ref>
			==Marine animals==
			Trimethylamine ''N''-oxide is an ] found in molluscs, crustaceans, and all marine fishes and bony fishes. It is a protein stabilizer that serves to counteract the protein-destabilizing effects of pressure. In general, the bodies of animals living at great depths are adapted to high pressure environments by having pressure-resistant biomolecules and small organic molecules present in their cells, known as piezolytes, of which TMAO is the most abundant. These piezolytes give the proteins the flexibility they need to function properly under great pressure.<ref name=Linley2016/><ref name=Gerringer2017/><ref>{{cite journal |author=Yancey, P. |title=Organic osmolytes as compatible, metabolic, and counteracting cytoprotectants in high osmolarity and other stresses |journal=] |year=2005 |volume=208 |pages= 2819–2830 |doi=10.1242/jeb.01730 |pmid= 16043587 |issue=15|doi-access=free }}</ref><ref>{{cite journal|first1=M.T.|last1=Velasquez|first2=A.|last2=Ramezani|first3=A.|last3=Manal| first4=D.S.|last4=Raj|title=Trimethylamine N-Oxide: The good, the bad and the unknown|date=8 November 2016|journal=Toxins|volume=8|issue=11|pages = 326|doi=10.3390/toxins8110326|pmid=27834801|pmc=5127123|doi-access=free}}</ref><ref name="JetfZ">{{cite web |url=https://www.bbc.co.uk/earth/story/20150129-life-at-the-bottom-of-the-ocean |title=What does it take to live at the bottom of the ocean? |year=2016 |publisher=BBC Earth |access-date=19 May 2016 |archive-date=13 May 2016 |archive-url=https://web.archive.org/web/20160513205236/http://www.bbc.co.uk/earth/story/20150129-life-at-the-bottom-of-the-ocean |url-status=live}}</ref>
			TMAO decomposes to ] (TMA), which is the main ] that is characteristic of degrading seafood.{{cn|date=November 2024}}
			==TMAO in diet==
			TMAO levels increase with consumption of ] protein such as eggs, ], shellfish and total ] consumption.<ref>{{cite journal|author=Yang JJ, Shu XO, Herrington DM, Moore SC, Meyer KA, Ose J, Menni C, Palmer ND, Eliassen H, Harada S, Tzoulaki I, Zhu H, Albanes D, Wang TJ, Zheng W, Cai H, Ulrich CM, Guasch-Ferré M, Karaman I, Fornage M, Cai Q, Matthews CE, Wagenknecht LE, Elliott P, Gerszten RE, Yu D.|year=2021|title=Circulating trimethylamine N-oxide in association with diet and cardiometabolic biomarkers: an international pooled analysis|journal=The American Journal of Clinical Nutrition|volume=113|issue=5|pages=1145–1156|doi=10.1093/ajcn/nqaa430|pmid=33826706|pmc=8106754 |hdl=10044/1/86226|hdl-access=free}}</ref><ref name="Lombardo 2022">{{cite journal|author=Lombardo M, Aulisa G, Marcon D, Rizzo G.|year=2022|title=The Influence of Animal- or Plant-Based Diets on Blood and Urine Trimethylamine-N-Oxide (TMAO) Levels in Humans|journal=Curr Nutr Rep|url=|volume=11|issue=1|pages=56–68|doi=10.1007/s13668-021-00387-9|pmid=34990005}}</ref> ]s such as vegan, vegetarian and the ] lower TMAO levels.<ref name="Lombardo 2022"/><ref>{{cite journal|author=Evans M, Dai L, Avesani CM, Kublickiene K, Stenvinkel P.|year=2023|title=The dietary source of trimethylamine N-oxide and clinical outcomes: an unexpected liaison|journal=Clin Kidney J|url=https://academic.oup.com/ckj/article/16/11/1804/7136173|volume=16|issue=11|pages=1804–1812|doi=10.1093/ckj/sfad095|pmid=37915930|pmc=10616480}}</ref>
			==Chemistry==
			TMAO can be synthesized from TMA by treatment with ]:<ref name=EROS>A. J. Pearson "Trimethylamine N-Oxide" in ''Encyclopedia of Reagents for Organic Synthesis'', John Wiley & Sons, 2001: New York. {{doi|10.1002/047084289X.rt268}}</ref>
			:<chem>H2O2 + (CH3)3N -> H2O + (CH3)3NO</chem>
			The dihydrate is dehydrated by azeotropic distillation from ].<ref>{{cite journal|author1=Soderquist, J. A. |author2=Anderson, C. L. |title=Crystalline anhydrous trimethylamine N-oxide|journal=Tetrahedron Lett.|year=1986|volume=27|issue=34|pages=3961–3962|doi=10.1016/S0040-4039(00)84884-4}}</ref>
			===Laboratory applications===
			Trimethylamine oxide is used in ] experiments to counteract the unfolding effects of ].<ref>{{cite journal |author=Zou, Q. |title=The Molecular Mechanism of Stabilization of Proteins by TMAO and Its Ability to Counteract the Effects of Urea |journal=] |year=2002 |volume=124 |issue=7 |pages= 1192–1202 |doi=10.1021/ja004206b |pmid=11841287 |last2=Bennion |first2=Brian J. |last3=Daggett |first3=Valerie |last4=Murphy |first4=Kenneth P.}}</ref>
			In the ] reaction of ], Me<sub>3</sub>NO is employed as a decarbonylation agent according to the following ]:
			:M(CO)<sub>''n''</sub> + Me<sub>3</sub>NO + L → M(CO)<sub>''n''−1</sub>L + Me<sub>3</sub>N + CO<sub>2</sub>
			This reaction is used to decomplex organic ligands from metals, e.g. from (diene)Fe(CO)<sub>3</sub>.<ref name=EROS/>
			It is used in certain oxidation reactions, e.g. the conversion of alkyl iodides to the corresponding ].<ref>{{OrgSynth |author= Volker Franzen |title= Octanal |collvol= 5 |collvolpages= 872 |prep= cv5p0872 |year= 1973}}</ref>
			====Effects on protein stability====
			The effects of TMAO on the backbone and charged residues of peptides are found to stabilize compact conformations,<ref>{{cite journal|date=2015-03-03|title=Regulation and aggregation of intrinsically disordered peptides|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=112|issue=9|pages=2758–2763|doi=10.1073/pnas.1418155112|pmid=25691742|pmc=4352815|last1=Shea|first1=Joan-Emma|last2=Feinstein|first2=Stuart C.|last3=Lapointe|first3=Nichole E.|last4=Larini|first4=Luca|last5=Levine|first5=Zachary A.|bibcode=2015PNAS..112.2758L|doi-access=free}}</ref> whereas effects of TMAO on nonpolar residues lead to peptide swelling. This suggests competing mechanisms of TMAO on proteins, which accounts for hydrophobic swelling, backbone collapse, and stabilization of charge-charge interactions. These mechanisms are observed in Trp cage.<ref>{{cite journal|title=Effects of Trimethylamine-N-oxide on the Conformation of Peptides and its Implications for Proteins|journal=Physical Review Letters|volume=119|issue=10|pages=108102|doi=10.1103/physrevlett.119.108102|pmid=28949191|year=2017|last1=Su|first1=Zhaoqian|last2=Mahmoudinobar|first2=Farbod|last3=Dias|first3=Cristiano L.|bibcode=2017PhRvL.119j8102S}}</ref>
			==Disorders==
			===Trimethylaminuria===
			{{Main|Trimethylaminuria}}
			] is a rare defect in the production of the enzyme ] (''FMO3'').<ref>{{cite journal |author=Treacy, E.P. |title=Mutations of the flavin-containing monooxygenase gene (''FMO3'') cause trimethylaminuria, a defect in detoxication |journal=Human Molecular Genetics |year=1998 |pages=839–45 |volume=7 |issue=5 |doi=10.1093/hmg/7.5.839 |pmid=9536088 |last2=Akerman |first2=BR |last3=Chow |first3=LM |last4=Youil |first4=R |last5=Bibeau |first5=C |last6=Lin |first6=J |last7=Bruce |first7=AG |last8=Knight |first8=M |last9=Danks |first9=DM|doi-access=free }}</ref><ref>{{cite journal |vauthors=Zschocke J, Kohlmueller D, Quak E, Meissner T, Hoffmann GF, Mayatepek E |title=Mild trimethylaminuria caused by common variants in FMO3 gene |journal=Lancet |year=1999 |pages=834–5 |volume=354 |issue=9181 |pmid=10485731 |doi=10.1016/S0140-6736(99)80019-1|s2cid=9555588 }}</ref> Those suffering from trimethylaminuria are unable to convert choline-derived trimethylamine into trimethylamine oxide. Trimethylamine then accumulates and is released in the person's sweat, urine, and breath, giving off a strong fishy odor.{{cn|date=November 2024}}
			== Health effects ==
			=== Mortality ===
			High ] are associated with an increased risk of all-cause ].<ref name="Schiattarella" /><ref name=":0">{{cite journal |author=Guasti L, Galliazzo S, Molaro M, Visconti E, Pennella B, Gaudio GV, Lupi A, Grandi AM, Squizzato A. |year=2021 |title=TMAO as a biomarker of cardiovascular events: a systematic review and meta-analysis |url= |journal=Intern Emerg Med |volume=16 |issue=1 |pages=201–207 |doi=10.1007/s11739-020-02470-5 |pmid=32779113 |s2cid=221099557}}</ref>
			===Cardiovascular disease===
			High circulating TMAO concentrations are associated with an increased risk of ]<ref name="Schiattarella" /><ref name=":0" /> and ]s in particular.<ref>{{cite journal |author=Zhang H, Yao G. |year=2023 |title=Significant correlation between the gut microbiota-derived metabolite trimethylamine-N-oxide and the risk of stroke: evidence based on 23 observational studies |journal=European Journal of Clinical Nutrition |volume=77 |issue=7 |pages=731–740 |doi=10.1038/s41430-022-01104-7 |pmid=35468932 |s2cid=248368447}}</ref>
			===Hypertension===
			High circulating TMAO concentrations are associated with an increased risk of ].<ref>{{cite journal|year=2020|author=Ge X, Zheng L, Zhuang R, Yu P, Xu Z, Liu G, Xi X, Zhou X, Fan H.|title=The Gut Microbial Metabolite Trimethylamine N-Oxide and Hypertension Risk: A Systematic Review and Dose-Response Meta-analysis|journal=Adv Nutr|volume=11|issue=1|pages=66–76|doi=10.1093/advances/nmz064|pmid=31269204|pmc=7442397}}</ref><ref>{{cite journal|year=2024|author=Han JM, Guo L, Chen XH, Xie Q, Song XY, Ma YL.|title=Relationship between trimethylamine N-oxide and the risk of hypertension in patients with cardiovascular disease: A meta-analysis and dose-response relationship analysis|journal=Medicine (Baltimore)|volume=103|issue=1|pages=e36784|doi=10.1097/MD.0000000000036784|pmid=38181288|pmc=10766215}}</ref>
			===Potential toxicity===
			Exposure limit guidelines with a detailed description of toxicity are available such as "Recommendation from the Scientific Committee on Occupational Exposure Limits" by the European Union Commission.<ref>{{Cite book |last1=Directorate-General for Employment |first1=Social Affairs and Inclusion (European Commission) |last2=Scientific Committee on Occupational Exposure Limits |last3=Nielsen |first3=G. D. |last4=Pospischil |first4=E. |last5=Johanson |first5=G. |last6=Klein |first6=C. L. |last7=Papameletiou |first7=D. |date=2017 |title=SCOEL/REC/179 trimethylamine: recommendation from the Scientific Committee on Occupational Exposure Limits |url=https://data.europa.eu/doi/10.2767/440659 |access-date=2023-12-17 |publisher=Publications Office of the European Union|doi=10.2767/440659 |isbn=978-92-79-66627-8 }}</ref>
			==See also==
			* ]
			==References==
			{{Reflist|30em}}
			]
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