T3DB: Methylamine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (3)XML

Targets (3)

Record Information

Version

2.0

Creation Date

2014-08-29 05:46:57 UTC

Update Date

2014-12-24 20:26:40 UTC

Accession Number

T3D4151

Identification

Common Name

Methylamine

Class

Small Molecule

Description

Methylamine 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

MOL SDF PDB SMILES InChI

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 Formula

CH₅N

Average Molecular Mass

31.057 g/mol

Monoisotopic Mass

31.042 g/mol

CAS Registry Number

74-89-5

IUPAC Name

methanamine

Traditional Name

methylamine

SMILES

InChI Identifier

InChI=1S/CH5N/c1-2/h2H2,1H3

InChI Key

InChIKey=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.

Kingdom

Organic compounds

Super Class

Organic nitrogen compounds

Class

Organonitrogen compounds

Sub Class

Amines

Direct Parent

Monoalkylamines

Alternative Parents

Substituents

Organopnictogen compound
Hydrocarbon derivative
Primary aliphatic amine
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

one-carbon compound (CHEBI:16830 )
primary aliphatic amine (CHEBI:16830 )
methylamines (CHEBI:16830 )
a small molecule (METHYLAMINE )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Liquid

Appearance

Not Available

Experimental Properties

Property	Value
Melting Point	-93.4°C
Boiling Point	Not Available
Solubility	1080 mg/mL at 25°C
LogP	-0.57

Predicted Properties

Property	Value	Source
Water Solubility	367 g/L	ALOGPS
logP	-1.1	ALOGPS
logP	-0.63	ChemAxon
logS	1.07	ALOGPS
pKa (Strongest Basic)	10.08	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	1	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	26.02 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	9.92 m³·mol⁻¹	ChemAxon
Polarizability	3.86 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-001i-9000000000-50fb665f1ba89a03baf9	2017-08-28	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-001i-9000000000-93f5049fa2e67d0da26d	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-001i-9000000000-53c64a174764bada8913	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-001i-9000000000-1c10568342e547416eaf	2012-07-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-001i-9000000000-2910620cfb01718df17f	2017-07-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-001i-9000000000-2910620cfb01718df17f	2017-07-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-001i-9000000000-2910620cfb01718df17f	2017-07-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-001i-9000000000-f140127f4f4b677d2975	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-001i-9000000000-f140127f4f4b677d2975	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-001i-9000000000-f140127f4f4b677d2975	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-001i-9000000000-986b844d44ea8cab8877	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-001i-9000000000-986b844d44ea8cab8877	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-001i-9000000000-986b844d44ea8cab8877	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-001i-9000000000-d90d418cf76ae365e6c5	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-001i-9000000000-d90d418cf76ae365e6c5	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-001i-9000000000-d90d418cf76ae365e6c5	2021-09-22	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-001i-9000000000-43b9d7b881c659f2ceb1	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 125 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-16	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 400 MHz, H₂O, experimental)	Not Available	2012-12-05	View Spectrum

Toxicity Profile

Route of Exposure

Endogenous, Ingestion, Dermal (contact)

Mechanism of Toxicity

Uremic 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)

Metabolism

Uremic 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 Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Naturally produced by the body (endogenous).

Minimum Risk Level

Not Available

Health Effects

Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.

Symptoms

As 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.

Treatment

Kidney 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

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

16830

BioCyc ID

CPD-4521

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

NME

ACToR ID

Not Available

Wikipedia Link

Methylamine

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.

MSDS

Link

General References

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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. 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

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 ]
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

2. 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

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 ]
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

3. 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

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 ]
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 ]

Methylamine (T3D4151)

Structure for T3D4151: Methylamine

Targets

References

References

References