Trimethylamine oxide

Names

[ Name ]:
Trimethylamine oxide

[Synonym ]:
TMAO
N,N-Dimethylmethanamine N-oxide
EINECS 214-675-6
Amine oxide, trimethyl-
Triox
anhydrous trimethylamine oxide
TriMethylaMine N-Oxide
N,N-dimethylmethanamine oxide
Methanamine,N,N-dimethyl-,N-oxide
trimethylamine-N-oxide
Trimethylamine oxide
Triméthylamine-oxyde
Trimethylamineoxid
MFCD00002048
Trimethyloxamine

Biological Activity

[Description]:

Trimethylamine N-oxide is a gut microbe-dependent metabolite of dietary choline and other trimethylamine-containing nutrients. Trimethylamine N-oxide induces inflammation by activating the ROS/NLRP3 inflammasome. Trimethylamine N-oxide also accelerates fibroblast-myofibroblast differentiation and induces cardiac fibrosis by activating the TGF-β/smad2 signaling pathway[1][2][3].

[Related Catalog]:

Signaling Pathways >> Stem Cell/Wnt >> TGF-beta/Smad

Research Areas >> Cardiovascular Disease

Signaling Pathways >> TGF-beta/Smad >> TGF-beta/Smad

Signaling Pathways >> Immunology/Inflammation >> NOD-like Receptor (NLR)

Research Areas >> Inflammation/Immunology

[Target]

ROS/NLRP3 inflammasome[1] TGF-β/smad2[1]

[In Vitro]

The size and migration of fibroblasts are increased after Trimethylamine N-oxide (TMAO) treatment compared with non-treated fibroblasts in vitro. Trimethylamine N-oxide increases TGF-β receptor I expression, which promotes the phosphorylation of Smad2 and up-regulates the expression of α-SMA and collagen I. The ubiquitination of TGF-βRI is decreased in neonatal mouse fibroblasts after Trimethylamine N-oxide treatment. Trimethylamine N-oxide also inhibits the expression of smurf2[2]. Trimethylamine N-oxide is frequently found in the tissues of a variety of marine organisms that protects against the adverse effects of temperature, salinity, high urea and hydrostatic pressure[3].

[In Vivo]

Trimethylamine N-oxide (TMAO) contributes to cardiovascular diseases by promoting inflammatory responses. C57BL/6 mice are fed a normal diet, high-choline diet and/or 3-dimethyl-1-butanol (DMB) diet. The levels of Trimethylamine N-oxide and choline are increased in choline-fed mice. Left ventricular hypertrophy, pulmonary congestion, and diastolic dysfunction are markedly exacerbated in heart failure with preserved ejection fraction (HFpEF) mice fed high-choline diets compared with mice fed the control diet. Myocardial fibrosis and inflammation were markedly increased in HFpEF mice fed high-choline diets compared with animals fed the control diet[1].

[References]

[1]. Wei Shuai, et al. High-choline Diet Exacerbates Cardiac Dysfunction, Fibrosis, and Inflammation in a Mouse Model of Heart Failure With Preserved Ejection Fraction. J Card Fail. 2020 May 14;S1071-9164(19)31802-0.

[2]. Wenlong Yang, et al. Gut Microbe-Derived Metabolite Trimethylamine N-oxide Accelerates Fibroblast-Myofibroblast Differentiation and Induces Cardiac Fibrosis. J Mol Cell Cardiol. 2019 Sep;134:119-130.

[3]. Manuel T Velasquez, et al. Trimethylamine N-Oxide: The Good, the Bad and the Unknown. Toxins (Basel). 2016 Nov 8;8(11):326.

Chemical & Physical Properties

[ Density]:
0.9301 (rough estimate)

[ Boiling Point ]:
133.8°C (rough estimate)

[ Melting Point ]:
220-222ºC(lit.)

[ Molecular Formula ]:
C₃H₉NO

[ Molecular Weight ]:
75.110

[ Exact Mass ]:
75.068413

[ PSA ]:
29.43000

[ LogP ]:
-2.57

[ Index of Refraction ]:
1.4698 (estimate)

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi: Irritant;

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
26-37/39

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ HS Code ]:
2921110090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2921110090

[ Summary ]:
HS: 2921110090. methylamine, di- or trimethylamine and their salts. VAT:17.0%. tax rebate rate:9.0%. supervision conditions:ab(certificate of inspection for goods inward,certificate of inspection for goods outward). MFN tariff:6.5%. general tariff:30.0%

Articles

HMDB: a knowledgebase for the human metabolome.

Nucleic Acids Res. 37(Database issue) , D603-10, (2009)

The Human Metabolome Database (HMDB, http://www.hmdb.ca) is a richly annotated resource that is designed to address the broad needs of biochemists, clinical chemists, physicians, medical geneticists, ...

Prediction of skeletal muscle and fat mass in patients with advanced cancer using a metabolomic approach.

J. Nutr. 142(1) , 14-21, (2012)

Urine and plasma metabolites originate from endogenous metabolic pathways in different organs and exogenous sources (diet). Urine and plasma were obtained from advanced cancer patients and investigate...

Gender-related and age-related urinalysis of healthy subjects by NMR-based metabonomics.

NMR Biomed. 21(3) , 195-207, (2008)

NMR-based metabonomic analysis is a well-established approach to characterizing healthy and diseased states. The aim of this study was to investigate inter-individual variability in the metabolic urin...