General Information of MET (ID: META00346)
Name Trimethylamine N-oxide
Synonyms   Click to Show/Hide Synonyms of This Metabolite
(CH3)3NO; Me3n(+)O(-); Me3n(O); N(CH3)3O; N,N-Dimethylmethanamine N-oxide; TMA-oxide; TMAO; Trimethylamine oxide; Trimethylamine-N-oxide; Trimethylaminoxid; Trimethylammonium oxide; Trimethyloxamine; Triox
Source Endogenous;Drug Metabolite;Escherichia Coli Metabolite;Food;Toxins/Pollutant;Food additives;Microbial
Structure Type   Aminoxides  (Click to Show/Hide the Complete Structure Type Hierarchy)
Organic nitrogen compounds
Organonitrogen compounds
Aminoxides
PubChem CID
1145
HMDB ID
HMDB0000925
Formula
C3H9NO
Structure
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3D MOL 2D MOL
  Click to Show/Hide the Molecular/Functional Data (External Links/Property/Function) of This Metabolite
KEGG ID
C01104
ChEBI ID
15724
FooDB ID
FDB010413
ChemSpider ID
1113
METLIN ID
5876
Physicochemical Properties Molecular Weight 75.11 Topological Polar Surface Area 18.1
XlogP -0.3 Complexity 28.4
Heavy Atom Count 5 Rotatable Bond Count N.A.
Hydrogen Bond Donor Count N.A. Hydrogen Bond Acceptor Count 1
Function
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 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. It has been identified as a uremic toxin according to the European Uremic Toxin Working Group. 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. 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. 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. Urinary TMAO is a biomarker for the consumption of fish, especially cold-water fish. Trimethylamine N-oxide is found to be associated with maple syrup urine disease and propionic acidemia, which are inborn errors of metabolism. TMAO can also be found in Bacteroidetes, Ruminococcus.
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      Apolipoprotein (Apo)
            Apolipoprotein A-II (APOA2) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation (-265T >C(rs5082)) of APOA2
                      Induced Change Trimethylamine N-oxide concentration: decrease (FC = 0.71)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Obesity [ICD-11: 5B81]
                      Details It is reported that mutation (-265T >C(rs5082)) of APOA2 leads to the decrease of trimethylamine N-oxide levels compared with control group.
      GPCR secretin (GPCR-2)
            Glucagon receptor (GCGR) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of Gcgr
                      Induced Change Trimethylamine N-oxide concentration: increase (FC = 1.7)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Type 2 diabetes mellitus [ICD-11: 5A11]
                      Details It is reported that knockout of GCGR leads to the increase of trimethylamine N-oxide levels compared with control group.
References
1 Epigenomics and metabolomics reveal the mechanism of the APOA2-saturated fat intake interaction affecting obesity. Am J Clin Nutr. 2018 Jul 1;108(1):188-200.
2 Polyomic profiling reveals significant hepatic metabolic alterations in glucagon-receptor (GCGR) knockout mice: implications on anti-glucagon therapies for diabetes. BMC Genomics. 2011 Jun 1;12:281.

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