Tmic
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Record Information
Version2.0
Creation Date2014-08-29 05:46:57 UTC
Update Date2014-12-24 20:26:40 UTC
Accession NumberT3D4151
Identification
Common NameMethylamine
ClassSmall Molecule
DescriptionMethylamine is a uremic toxin. Uremic toxins can be subdivided into three major groups based upon their chemical and physical characteristics: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as the phenols and 3) larger so-called middle-molecules, such as beta2-microglobulin. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. Methylamine occurs endogenously from amine catabolism and its tissue levels increase in some pathological conditions, including diabetes. Interestingly, methylamine and ammonia levels are reciprocally controlled by a semicarbazide-sensitive amine oxidase activity that deaminates methylamine to formaldehyde with the production of ammonia and hydrogen peroxide. Methylamine also targets the voltage-operated neuronal potassium channels, probably inducing release of neurotransmitter(s). Semicarbazide-sensitive amine oxidase (SSAO) catalyzes the deamination of primary amines. Such deamination has been shown capable of regulating glucose transport in adipose cells. It has been independently discovered that the primary structure of vascular adhesion protein-1 (VAP-1) is identical to SSAO. Increased serum SSAO activities have been found in patients with diabetic mellitus, vascular disorders and Alzheimer's disease. The SSAO-catalyzed deamination of endogenous substrates like methylamine led to production of toxic formaldehyde. Chronic elevated methylamine increases the excretion of malondialdehyde and microalbuminuria. Amine oxidase substrates such as methylamine have been shown to stimulate glucose uptake by increasing the recruitment of the glucose transporter GLUT4 from vesicles within the cell to the cell surface. Inhibition of this effect by the presence of semicarbazide and catalase led to the suggestion that the process is mediated by the H2O2 produced in the oxidation of these amines. (1, 2, 3).
Compound Type
  • Food Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Uremic Toxin
Chemical Structure
Thumb
Synonyms
Synonym
Aminomethane
Anhydrous methylamine
Carbinamine
Imizin
Mercurialin
Methanamine
Methyl group
Methyl of gamma-N-methylasparagine
Methylamine anhydrous
Methylamine aqueous solution
Methylamine solution
Methylamine solutions
Methylaminen
Metilamine
Metyloamina
MMA
Monomethylamine
N-Methylamine
NMA
NME
Chemical FormulaCH5N
Average Molecular Mass31.057 g/mol
Monoisotopic Mass31.042 g/mol
CAS Registry Number74-89-5
IUPAC Namemethanamine
Traditional Namemethylamine
SMILESCN
InChI IdentifierInChI=1S/CH5N/c1-2/h2H2,1H3
InChI KeyInChIKey=BAVYZALUXZFZLV-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as monoalkylamines. These are organic compounds containing an primary aliphatic amine group.
KingdomOrganic compounds
Super ClassOrganic nitrogen compounds
ClassOrganonitrogen compounds
Sub ClassAmines
Direct ParentMonoalkylamines
Alternative Parents
Substituents
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Primary aliphatic amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceNot Available
Experimental Properties
PropertyValue
Melting Point-93.4°C
Boiling PointNot Available
Solubility1080 mg/mL at 25°C
LogP-0.57
Predicted Properties
PropertyValueSource
Water Solubility367 g/LALOGPS
logP-1.1ALOGPS
logP-0.63ChemAxon
logS1.07ALOGPS
pKa (Strongest Basic)10.08ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area26.02 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity9.92 m³·mol⁻¹ChemAxon
Polarizability3.86 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-001i-9000000000-50fb665f1ba89a03baf9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-001i-9000000000-93f5049fa2e67d0da26dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-001i-9000000000-53c64a174764bada8913View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-001i-9000000000-1c10568342e547416eafView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-9000000000-2910620cfb01718df17fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-9000000000-2910620cfb01718df17fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-9000000000-2910620cfb01718df17fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-9000000000-f140127f4f4b677d2975View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-9000000000-f140127f4f4b677d2975View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-9000000000-f140127f4f4b677d2975View in MoNA
MSMass Spectrum (Electron Ionization)splash10-001i-9000000000-43b9d7b881c659f2ceb1View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureEndogenous, Ingestion, Dermal (contact)
Mechanism of ToxicityUremic toxins such as methylamine 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) (5). 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 (6)
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 ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesNaturally produced by the body (endogenous).
Minimum Risk LevelNot Available
Health EffectsChronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.
SymptomsAs a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.
TreatmentKidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01828
HMDB IDHMDB00164
PubChem Compound ID6329
ChEMBL IDCHEMBL43280
ChemSpider ID6089
KEGG IDC00218
UniProt IDNot Available
OMIM ID
ChEBI ID16830
BioCyc IDCPD-4521
CTD IDNot Available
Stitch IDNot Available
PDB IDNME
ACToR IDNot Available
Wikipedia LinkMethylamine
References
Synthesis Reference

Charles Pigerol, Pierre Eymard, Jean-Claude Vernieres, Jean-Pierre Werbenec, “Active derivatives of methylamine, therapeutic compositions containing the same and processes for preparing the said derivatives and compositions.” U.S. Patent US4026925, issued March, 1956.

MSDSLink
General References
  1. Pirisino R, Ghelardini C, De Siena G, Malmberg P, Galeotti N, Cioni L, Banchelli G, Raimondi L: Methylamine: a new endogenous modulator of neuron firing? Med Sci Monit. 2005 Aug;11(8):RA257-61. Epub 2005 Jul 25. [16049393 ]
  2. Yu PH, Wright S, Fan EH, Lun ZR, Gubisne-Harberle D: Physiological and pathological implications of semicarbazide-sensitive amine oxidase. Biochim Biophys Acta. 2003 Apr 11;1647(1-2):193-9. [12686132 ]
  3. McDonald A, Tipton K, O'Sullivan J, Olivieri A, Davey G, Coonan AM, Fu W: Modelling the roles of MAO and SSAO in glucose transport. J Neural Transm. 2007;114(6):783-6. Epub 2007 Apr 5. [17406961 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. Wolfe CL, Warrington JA, Davis S, Green S, Norcum MT: Isolation and characterization of human nuclear and cytosolic multisynthetase complexes and the intracellular distribution of p43/EMAPII. Protein Sci. 2003 Oct;12(10):2282-90. [14500886 ]
  8. Wolkers WF, Looper SA, Fontanilla RA, Tsvetkova NM, Tablin F, Crowe JH: Temperature dependence of fluid phase endocytosis coincides with membrane properties of pig platelets. Biochim Biophys Acta. 2003 Jun 10;1612(2):154-63. [12787933 ]
  9. Stanic P, Tandara M, Sonicki Z, Simunic V, Radakovic B, Suchanek E: Comparison of protective media and freezing techniques for cryopreservation of human semen. Eur J Obstet Gynecol Reprod Biol. 2000 Jul;91(1):65-70. [10817881 ]
  10. Zeisel SH, Gettner S, Youssef M: Formation of aliphatic amine precursors of N-nitrosodimethylamine after oral administration of choline and choline analogues in the rat. Food Chem Toxicol. 1989 Jan;27(1):31-4. [2703191 ]
  11. O'Sullivan J, Unzeta M, Healy J, O'Sullivan MI, Davey G, Tipton KF: Semicarbazide-sensitive amine oxidases: enzymes with quite a lot to do. Neurotoxicology. 2004 Jan;25(1-2):303-15. [14697905 ]
  12. 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 ]
  13. Sawetawan C, Bruns ES, Prins GS: Improvement of post-thaw sperm motility in poor quality human semen. Fertil Steril. 1993 Oct;60(4):706-10. [8405530 ]
  14. Gunnarsson M, Sundstrom P, Stigbrand T, Jensen PE: Native and transformed alpha2-macroglobulin in plasma from patients with multiple sclerosis. Acta Neurol Scand. 2003 Jul;108(1):16-21. [12807388 ]
  15. Kokubo T, Kushitani H, Sakka S, Kitsugi T, Yamamuro T: Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W. J Biomed Mater Res. 1990 Jun;24(6):721-34. [2361964 ]
  16. Mashige F, Imai K, Osuga T: A simple and sensitive assay of total serum bile acids. Clin Chim Acta. 1976 Jul 1;70(1):79-86. [947625 ]
  17. Wosikowski K, Biedermann E, Rattel B, Breiter N, Jank P, Loser R, Jansen G, Peters GJ: In vitro and in vivo antitumor activity of methotrexate conjugated to human serum albumin in human cancer cells. Clin Cancer Res. 2003 May;9(5):1917-26. [12738750 ]
  18. 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 ]
  19. Tencer J, Thysell H, Andersson K, Grubb A: Long-term stability of albumin, protein HC, immunoglobulin G, kappa- and lambda-chain-immunoreactivity, orosomucoid and alpha 1-antitrypsin in urine stored at -20 degrees C. Scand J Urol Nephrol. 1997 Feb;31(1):67-71. [9060087 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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. 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 ]
  2. 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 ]
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. 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 ]
  2. 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 ]
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. 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 ]
  2. 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 ]