Symmetric dimethylarginine (CHEM003136)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (4)XML
Record Information
Version1.0
Creation Date2014-08-29 05:49:47 UTC
Update Date2026-05-14 17:33:54 UTC
Accession NumberCHEM003136
Identification
Common NameSymmetric dimethylarginine
ClassSmall Molecule
DescriptionSymmetric dimethylarginine 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. Symmetric dimethylarginine (SDMA) is an endogenously produced inhibitor of nitric oxide synthase (EC-Number 1.14.13.39). However, elevated levels of SDMA occur in patients with vascular disease, especially suffering end-stage renal disease. (2).
Contaminant Sources
  • FooDB Chemicals
  • HMDB Contaminants - Urine
  • T3DB toxins
Contaminant Type
  • Amide
  • Amine
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Uremic Toxin
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
(2S)-2-Amino-5-(n',n''-dimethylcarbamimidamido)pentanoic acidChEBI
(S)-2-Amino-5-(n',n''-dimethylguanidino)pentanoic acidChEBI
Guanidino-N(1),N(2)-dimethylarginineChEBI
N(g1),N(g2)-DimethylarginineChEBI
N,N'-dimethylarginineChEBI
N(3),N(4)-Dimethyl-L-arginineChEBI
N(3),N(4)-DimethylarginineChEBI
N5-((Methylamino)(methylimino)methyl)-L-ornithineChEBI
N(5)-(N,N'-dimethylamidino)-L-ornithineChEBI
N(5)-(N,N'-dimethylcarbamimidoyl)-L-ornithineChEBI
N(5)-[Bis(methylamino)methylene]-L-ornithineChEBI
N(g),N'(g)-dimethyl-L-arginineChEBI
N(g),N'(g)-dimethylarginineChEBI
SDMAChEBI
(2S)-2-Amino-5-(n',n''-dimethylcarbamimidamido)pentanoateGenerator
(S)-2-Amino-5-(n',n''-dimethylguanidino)pentanoateGenerator
N5-(N,N'-dimethylamidino)-L-ornithineHMDB
N5-[Bis(methylamino)methylene]-L-ornithineHMDB
NG,N'G-dimethyl-L-arginineHMDB, MeSH
NG,N'G-dimethylarginineHMDB
NG,NG'-dimethylarginineHMDB
Omega-N(g),n'(g)-dimethylarginineMeSH, HMDB
SDMA arginineMeSH, HMDB
Chemical FormulaC8H18N4O2
Average Molecular Mass202.254 g/mol
Monoisotopic Mass202.143 g/mol
CAS Registry Number30344-00-4
IUPAC Name(2S)-2-amino-5-[(Z)-N',N''-dimethylcarbamimidamido]pentanoic acid
Traditional NameN3, N4-dimethylarginine
SMILESCN\C(NCCC[C@H](N)C(O)=O)=N/C
InChI IdentifierInChI=1S/C8H18N4O2/c1-10-8(11-2)12-5-3-4-6(9)7(13)14/h6H,3-5,9H2,1-2H3,(H,13,14)(H2,10,11,12)/t6-/m0/s1
InChI KeyHVPFXCBJHIIJGS-LURJTMIESA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as arginine and derivatives. Arginine and derivatives are compounds containing arginine or a derivative thereof resulting from reaction of arginine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentArginine and derivatives
Alternative Parents
Substituents
  • Arginine or derivatives
  • Alpha-amino acid
  • L-alpha-amino acid
  • Fatty acid
  • Guanidine
  • Amino acid
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Carboximidamide
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Amine
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Primary aliphatic amine
  • Imine
  • Organic oxygen compound
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Kidney
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
Predicted Properties
PropertyValueSource
Water Solubility1.56 g/LALOGPS
logP-2.9ALOGPS
logP-2.7ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)2.54ChemAxon
pKa (Strongest Basic)12.4ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area99.74 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity53.18 m³·mol⁻¹ChemAxon
Polarizability22.22 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0kfx-9600000000-f6c986d30ea287579a78Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0fkc-9720000000-0f297fd1183458956770Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-00di-9600000000-a9cb6507d9fe3ffb39aaSpectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Negativesplash10-053r-3910000000-1a8526e47c9af75d4cc9Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Negativesplash10-0a59-9400000000-777d41b210dd091439b4Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0pbi-1930000000-98ffa2f50a3e5ee90e10Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0abi-8900000000-eccaa3c6c71a7aab8dd3Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-9000000000-fd3f3045e508262e68beSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-3390000000-ec3717ed507fec531202Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-9520000000-06ed24b7ccb74ccd705bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00dr-9000000000-40bdb35b370bc3317a55Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-2190000000-1ff257e4be06b9702e65Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-9100000000-b9dfe8a8d6f891dcecbfSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-9000000000-926c9fc48c09f4030499Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0ue9-1590000000-567e7d20ebbf052f8d39Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-2900000000-84e3189b175eab73e2c5Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9000000000-c8ec00d7abbc06aa7e4cSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
Toxicity Profile
Route of ExposureEndogenous, Ingestion, Dermal (contact)
Mechanism of ToxicityUremic toxins such as symmetric dimethylarginine 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) (3). 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 (4).
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.
Concentrations
Not Available
DrugBank IDDB02302
HMDB IDHMDB0003334
FooDB IDFDB000509
Phenol Explorer IDNot Available
KNApSAcK IDC00052415
BiGG IDNot Available
BioCyc IDNot Available
METLIN ID6891
PDB IDNot Available
Wikipedia LinkNot Available
Chemspider ID147942
ChEBI ID25682
PubChem Compound ID169148
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
1. https://www.ncbi.nlm.nih.gov/pubmed/?term=11437716
2. https://www.ncbi.nlm.nih.gov/pubmed/?term=11950212
3. https://www.ncbi.nlm.nih.gov/pubmed/?term=12466365
4. https://www.ncbi.nlm.nih.gov/pubmed/?term=12782025
5. https://www.ncbi.nlm.nih.gov/pubmed/?term=15494416
6. https://www.ncbi.nlm.nih.gov/pubmed/?term=15827267
7. https://www.ncbi.nlm.nih.gov/pubmed/?term=16182327
8. https://www.ncbi.nlm.nih.gov/pubmed/?term=16380646
9. https://www.ncbi.nlm.nih.gov/pubmed/?term=17709427
10. https://www.ncbi.nlm.nih.gov/pubmed/?term=18515076
11. https://www.ncbi.nlm.nih.gov/pubmed/?term=18815077
12. https://www.ncbi.nlm.nih.gov/pubmed/?term=19668105
13. https://www.ncbi.nlm.nih.gov/pubmed/?term=19803415
14. https://www.ncbi.nlm.nih.gov/pubmed/?term=20936901
15. https://www.ncbi.nlm.nih.gov/pubmed/?term=21278301
16. https://www.ncbi.nlm.nih.gov/pubmed/?term=21303648
17. Zinellu Angelo; Sotgia Salvatore; Scanu Bastianina; Formato Marilena; Deiana Luca; Carru Ciriaco Assessment of protein-incorporated arginine methylation in biological specimens by CZE UV-detection. Electrophoresis (2007), 28(23), 4452-8.
18. Fleck C, Schweitzer F, Karge E, Busch M, Stein G: Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in patients with chronic kidney diseases. Clin Chim Acta. 2003 Oct;336(1-2):1-12.
19. Boger RH, Bode-Boger SM, Szuba A, Tsao PS, Chan JR, Tangphao O, Blaschke TF, Cooke JP: Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation. 1998 Nov 3;98(18):1842-7.
20. Martens-Lobenhoffer J, Bode-Boger SM: Measurement of asymmetric dimethylarginine (ADMA) in human plasma: from liquid chromatography estimation to liquid chromatography-mass spectrometry quantification. Eur J Clin Pharmacol. 2006 Feb;62(Supplement 13):61-68.
21. Nijveldt RJ, Van Leeuwen PA, Van Guldener C, Stehouwer CD, Rauwerda JA, Teerlink T: Net renal extraction of asymmetrical (ADMA) and symmetrical (SDMA) dimethylarginine in fasting humans. Nephrol Dial Transplant. 2002 Nov;17(11):1999-2002.
22. Schiel R, Franke S, Busch M, Muller A, Fleck C, Muller UA, Braun A, Stein G: Effect of smoking on risk factors for cardiovascular disease in patients with diabetes mellitus and renal insufficiency. Eur J Med Res. 2003 Jul 31;8(7):283-91.
23. Mittermayer F, Pleiner J, Krzyzanowska K, Wiesinger GF, Francesconi M, Wolzt M: Regular physical exercise normalizes elevated asymmetrical dimethylarginine concentrations in patients with type 1 diabetes mellitus. Wien Klin Wochenschr. 2005 Dec;117(23-24):816-20.
24. Krzyzanowska K, Mittermayer F, Schnack C, Hofer M, Wolzt M, Schernthaner G: Circulating ADMA concentrations are elevated in hypopituitary adults with and without growth hormone deficiency. Eur J Clin Invest. 2005 Mar;35(3):208-13.
25. Marliss EB, Chevalier S, Gougeon R, Morais JA, Lamarche M, Adegoke OA, Wu G: Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover. Diabetologia. 2006 Feb;49(2):351-9. Epub 2005 Dec 21.
26. Schmidt RJ, Baylis C: Total nitric oxide production is low in patients with chronic renal disease. Kidney Int. 2000 Sep;58(3):1261-6.
27. Ellis J, Wennerholm UB, Bengtsson A, Lilja H, Pettersson A, Sultan B, Wennergren M, Hagberg H: Levels of dimethylarginines and cytokines in mild and severe preeclampsia. Acta Obstet Gynecol Scand. 2001 Jul;80(7):602-8.
28. Wang J, Sim AS, Wang XL, Salonikas C, Naidoo D, Wilcken DE: Relations between plasma asymmetric dimethylarginine (ADMA) and risk factors for coronary disease. Atherosclerosis. 2006 Feb;184(2):383-8. Epub 2005 Jun 6.
29. Teerlink T, Neele SJ, de Jong S, Netelenbos JC, Stehouwer CD: Oestrogen replacement therapy lowers plasma levels of asymmetrical dimethylarginine in healthy postmenopausal women. Clin Sci (Lond). 2003 Jul;105(1):67-71.
30. Mittermayer F, Namiranian K, Pleiner J, Schaller G, Wolzt M: Acute Escherichia coli endotoxaemia decreases the plasma l-arginine/asymmetrical dimethylarginine ratio in humans. Clin Sci (Lond). 2004 Jun;106(6):577-81.
31. 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.
32. Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043.