Trimethylamine

Relevant Data

Food Additives Approved in the United States:

Food Additives Approved by WHO:

General Information

Chemical nameTrimethylamine
CAS number75-50-3
COE number10497
JECFA number1610
Flavouring typesubstances
FL No.11.009
MixtureNo
Purity of the named substance at least 95% unless otherwise specified
Reference bodyEFSA

From webgate.ec.europa.eu

Computed Descriptors

Download SDF
2D Structure
CID1146
IUPAC NameN,N-dimethylmethanamine
InChIInChI=1S/C3H9N/c1-4(2)3/h1-3H3
InChI KeyGETQZCLCWQTVFV-UHFFFAOYSA-N
Canonical SMILESCN(C)C
Molecular FormulaC3H9N
Wikipediatrimethylamine

From Pubchem

Computed Properties

Property Name Property Value
Molecular Weight59.112
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count1
Rotatable Bond Count0
Complexity8.0
CACTVS Substructure Key Fingerprint A A A D c c B C A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A F A A A A A A A A A A A A A Q C A A M A A A A A A A A A A A A A A A A A A A A A A A A I A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = =
Topological Polar Surface Area3.2
Monoisotopic Mass59.073
Exact Mass59.073
XLogP3None
XLogP3-AA0.3
Compound Is CanonicalizedTrue
Formal Charge0
Heavy Atom Count4
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

From Pubchem

Food Additives Biosynthesis/Degradation

ADMET Predicted Profile --- Classification

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.9596
Human Intestinal AbsorptionHIA+0.9601
Caco-2 PermeabilityCaco2+0.6932
P-glycoprotein SubstrateNon-substrate0.8240
P-glycoprotein InhibitorNon-inhibitor0.9670
Non-inhibitor0.9824
Renal Organic Cation TransporterNon-inhibitor0.8590
Distribution
Subcellular localizationLysosome0.7284
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8198
CYP450 2D6 SubstrateNon-substrate0.8046
CYP450 3A4 SubstrateNon-substrate0.6002
CYP450 1A2 InhibitorNon-inhibitor0.8897
CYP450 2C9 InhibitorNon-inhibitor0.9536
CYP450 2D6 InhibitorNon-inhibitor0.9610
CYP450 2C19 InhibitorNon-inhibitor0.9508
CYP450 3A4 InhibitorNon-inhibitor0.9587
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.9184
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9316
Non-inhibitor0.9001
AMES ToxicityNon AMES toxic0.9133
CarcinogensCarcinogens 0.7793
Fish ToxicityLow FHMT0.7221
Tetrahymena Pyriformis ToxicityLow TPT0.9920
Honey Bee ToxicityHigh HBT0.6993
BiodegradationNot ready biodegradable0.7047
Acute Oral ToxicityII0.7608
Carcinogenicity (Three-class)Non-required0.5899

From admetSAR

ADMET Predicted Profile --- Regression

Model Value Unit
Absorption
Aqueous solubility0.4577LogS
Caco-2 Permeability1.5693LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.0604LD50, mol/kg
Fish Toxicity2.4815pLC50, mg/L
Tetrahymena Pyriformis Toxicity-1.4386pIGC50, ug/L

From admetSAR

Toxicity Profile

Route of ExposureEndogenous, Ingestion, Dermal (contact)
Mechanism of ToxicityUremic toxins such as trimethylamine are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) . Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species .
MetabolismUremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.
Toxicity ValuesNone
Lethal DoseNone
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk LevelNone
Health EffectsChronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.
TreatmentKidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored.
Reference
  1. Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A: Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 2012 Jul;23(7):1258-70. doi: 10.1681/ASN.2011121175. Epub 2012 May 24.[22626821 ]
  2. 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 ]
  3. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297.[25041433 ]
  4. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461.[22419041 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. Hillier SL: Diagnostic microbiology of bacterial vaginosis. Am J Obstet Gynecol. 1993 Aug;169(2 Pt 2):455-9.[8357044 ]
  9. Chao CK, Zeisel SH: Formation of trimethylamine from dietary choline by Streptococcus sanguis I, which colonizes the mouth. J Nutr Biochem. 1990 Feb;1(2):89-97.[15539190 ]
  10. Dzik-Jurasz AS, Prescot AP, Leach MO, Collins DJ: Non-invasive study of human gall bladder bile in vivo using (1)H-MR spectroscopy. Br J Radiol. 2003 Jul;76(907):483-6.[12857709 ]
  11. Leys D, Basran J, Talfournier F, Chohan KK, Munro AW, Sutcliffe MJ, Scrutton NS: Flavin radicals, conformational sampling and robust design principles in interprotein electron transfer: the trimethylamine dehydrogenase-electron-transferring flavoprotein complex. Biochem Soc Symp. 2004;(71):1-14.[15777008 ]
  12. Zeisel SH, daCosta KA, LaMont JT: Mono-, di- and trimethylamine in human gastric fluid: potential substrates for nitrosodimethylamine formation. Carcinogenesis. 1988 Jan;9(1):179-81.[3335043 ]
  13. Mitchell SC, Zhang AQ, Barrett T, Ayesh R, Smith RL: Studies on the discontinuous N-oxidation of trimethylamine among Jordanian, Ecuadorian and New Guinean populations. Pharmacogenetics. 1997 Feb;7(1):45-50.[9110361 ]
  14. Al-Waiz M, Ayesh R, Mitchell SC, Idle JR, Smith RL: A genetic polymorphism of the N-oxidation of trimethylamine in humans. Clin Pharmacol Ther. 1987 Nov;42(5):588-94.[3677545 ]
  15. 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 ]
  16. Thithapandha A: A pharmacogenetic study of trimethylaminuria in Orientals. Pharmacogenetics. 1997 Dec;7(6):497-501.[9429235 ]

From T3DB

Taxonomic Classification

KingdomOrganic compounds
SuperclassOrganic nitrogen compounds
ClassOrganonitrogen compounds
SubclassAmines
Intermediate Tree NodesTertiary amines
Direct ParentTrialkylamines
Alternative Parents
Molecular FrameworkAliphatic acyclic compounds
SubstituentsTertiary aliphatic amine - Organopnictogen compound - Hydrocarbon derivative - Aliphatic acyclic compound
DescriptionThis compound belongs to the class of organic compounds known as trialkylamines. These are organic compounds containing a trialkylamine group, characterized by exactly three alkyl groups bonded to the amino nitrogen.

From ClassyFire

Targets

Target Details

Klotho

General Function:
Vitamin d binding
Specific Function:
May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity).The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling.
Gene Name:
KL
Uniprot ID:
Q9UEF7
Molecular Weight:
116179.815 Da
References
  1. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
Target Details

NADPH oxidase 4

General Function:
Superoxide-generating nadph oxidase activity
Specific Function:
Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 5 and isoform 6 display reduced activity.Isoform 4: Involved in redox signaling in vascular cells. Constitutively and NADPH-dependently generates reactive oxygen species (ROS). Modulates the nuclear activation of ERK1/2 and the ELK1 transcription factor, and is capable of inducing nuclear DNA damage. Displays an increased activity relative to isoform 1.
Gene Name:
NOX4
Uniprot ID:
Q9NPH5
Molecular Weight:
66930.995 Da
References
  1. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
Target Details

Solute carrier family 22 member 8

General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
  1. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]

From T3DB