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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:04:54 UTC
HMDB IDHMDB01539
Secondary Accession NumbersNone
Metabolite Identification
Common NameAsymmetric dimethylarginine
DescriptionAsymmetric dimethylarginine (ADMA) is a naturally occurring chemical found in blood plasma. It is a metabolic by-product of continual protein modification processes in the cytoplasm of all human cells. It is closely related to L-arginine, a conditionally-essential amino acid. ADMA interferes with L-arginine in the production of nitric oxide, a key chemical to endothelial and hence cardiovascular health. Asymmetric dimethylarginine is created in protein methylation, a common mechanism of post-translational protein modification. This reaction is catalyzed by an enzyme set called S-adenosylmethionine protein N-methyltransferases (protein methylases I and II). The methyl groups transferred to create ADMA are derived from the methyl group donor S-adenosylmethionine, an intermediate in the metabolism of homocysteine. (Homocysteine is an important blood chemical, because it is also a marker of cardiovascular disease). After synthesis, ADMA migrates into the extracellular space and thence into blood plasma. Asymmetric dimethylarginine is measured using high performance liquid chromatography.
Structure
Thumb
Synonyms
ValueSource
N,N-DimethylarginineKegg
Nomega,nomega-dimethyl-L-arginineKegg
ADMAKegg
2-amino-5-(amino-dimethylamino-Methylidene)amino-pentanoateHMDB
2-amino-5-(amino-dimethylamino-Methylidene)amino-pentanoic acidHMDB
Dimethyl-L-arginineHMDB
N(Omega),N(omega)-dimethyl-L-arginineHMDB
NG,NG-Dimethyl-L-arginineHMDB
NG,NG-DimethylarginineHMDB
NG-DimethylarginineHMDB
Nomega,nomega'-dimethyl-L-arginineHMDB
Chemical FormulaC8H18N4O2
Average Molecular Weight202.2541
Monoisotopic Molecular Weight202.14297584
IUPAC Name(2S)-2-amino-5-[(E)-[amino(dimethylamino)methylidene]amino]pentanoic acid
Traditional Nameasymmetric dimethylarginine
CAS Registry Number30315-93-6
SMILES
CN(C)C(=N)NCCC[C@H](N)C(O)=O
InChI Identifier
InChI=1S/C8H18N4O2/c1-12(2)8(10)11-5-3-4-6(9)7(13)14/h6H,3-5,9H2,1-2H3,(H2,10,11)(H,13,14)/t6-/m0/s1
InChI KeyInChIKey=YDGMGEXADBMOMJ-LURJTMIESA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as l-alpha-amino acids. These are alpha amino acids which have the L-configuration of the alpha-carbon atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentL-alpha-amino acids
Alternative Parents
Substituents
  • L-alpha-amino acid
  • Amino fatty acid
  • Fatty acyl
  • Fatty acid
  • Tertiary amine
  • Guanidine
  • Carboximidamide
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Imine
  • Carbonyl group
  • Amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Protein synthesis, amino acid biosynthesis
ApplicationNot Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point195 - 197 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility1.52 mg/mLALOGPS
logP-3.1ALOGPS
logP-2.7ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)2.54ChemAxon
pKa (Strongest Basic)12.34ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area104.94 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity53.7 m3·mol-1ChemAxon
Polarizability22.19 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Kidney
  • Liver
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified<0.30 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.35 (0.28-0.42) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.66 +/- 0.04 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.06 +/- 0.008 uMAdult (>18 years old)BothNormal details
UrineDetected and Quantified2.92 +/- 0.42 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified4.6 (3.00-7.00) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified15.2 +/- 3.0 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified2.7 (1.4-4.2) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified3.0 (0.2-6.7) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified4.35 +/- 0.19 uMAdult (>18 years old)Bothuremia details
BloodDetected and Quantified2.40 (1.30-3.50) uMAdult (>18 years old)BothEssential hypertension details
BloodDetected and Quantified0.91 +/- 0.04 uMAdult (>18 years old)Both
Kidney disease
details
BloodDetected and Quantified1.04 +/- 0.04 uMAdult (>18 years old)Both
Kidney disease
details
BloodDetected and Quantified0.87 +/- 0.04 uMAdult (>18 years old)Both
Kidney disease
details
BloodDetected and Quantified0.97 +/- 0.02 uMAdult (>18 years old)Both
Kidney disease
details
UrineDetected and Quantified22.0 +/- 4.0 umol/mmol creatinineAdult (>18 years old)BothAutosomal dominant polycystic kidney disease (ADPKD) details
Associated Disorders and Diseases
Disease References
Autosomal dominant polycystic kidney disease
  1. Wang D, Strandgaard S, Borresen ML, Luo Z, Connors SG, Yan Q, Wilcox CS: Asymmetric dimethylarginine and lipid peroxidation products in early autosomal dominant polycystic kidney disease. Am J Kidney Dis. 2008 Feb;51(2):184-91. [18215696 ]
Essential hypertension
  1. Surdacki A, Nowicki M, Sandmann J, Tsikas D, Boeger RH, Bode-Boeger SM, Kruszelnicka-Kwiatkowska O, Kokot F, Dubiel JS, Froelich JC: Reduced urinary excretion of nitric oxide metabolites and increased plasma levels of asymmetric dimethylarginine in men with essential hypertension. J Cardiovasc Pharmacol. 1999 Apr;33(4):652-8. [10218738 ]
Kidney disease
  1. 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. [14500028 ]
Associated OMIM IDs
  • 601313 (Autosomal dominant polycystic kidney disease)
DrugBank IDDB01686
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB000508
KNApSAcK IDNot Available
Chemspider ID110375
KEGG Compound IDC03626
BioCyc IDCPD-596
BiGG IDNot Available
Wikipedia LinkAsymmetric dimethylarginine
NuGOwiki LinkHMDB01539
Metagene LinkHMDB01539
METLIN ID6309
PubChem Compound123831
PDB IDDA2
ChEBI ID17929
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. van Guldener C, Nanayakkara PW, Stehouwer CD: Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease. Clin Chem Lab Med. 2007;45(12):1683-7. [17937610 ]
  2. Surdacki A, Nowicki M, Sandmann J, Tsikas D, Boeger RH, Bode-Boeger SM, Kruszelnicka-Kwiatkowska O, Kokot F, Dubiel JS, Froelich JC: Reduced urinary excretion of nitric oxide metabolites and increased plasma levels of asymmetric dimethylarginine in men with essential hypertension. J Cardiovasc Pharmacol. 1999 Apr;33(4):652-8. [10218738 ]
  3. 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. [16217682 ]
  4. Watanabe T, Kato S, Sato K, Nagata K: Nitric oxide regulation system in degenerative lumbar disease. Kurume Med J. 2005;52(1-2):39-47. [16119611 ]
  5. Nijveldt RJ, Teerlink T, Siroen MP, van der Hoven B, Prins HA, Wiezer MJ, Meijer C, van der Sijp JR, Cuesta MA, Meijer S, van Leeuwen PA: Elevation of asymmetric dimethylarginine (ADMA) in patients developing hepatic failure after major hepatectomy. JPEN J Parenter Enteral Nutr. 2004 Nov-Dec;28(6):382-7. [15568284 ]
  6. Siroen MP, Warle MC, Teerlink T, Nijveldt RJ, Kuipers EJ, Metselaar HJ, Tilanus HW, Kuik DJ, van der Sijp JR, Meijer S, van der Hoven B, van Leeuwen PA: The transplanted liver graft is capable of clearing asymmetric dimethylarginine. Liver Transpl. 2004 Dec;10(12):1524-30. [15558588 ]
  7. Tarnow L, Hovind P, Teerlink T, Stehouwer CD, Parving HH: Elevated plasma asymmetric dimethylarginine as a marker of cardiovascular morbidity in early diabetic nephropathy in type 1 diabetes. Diabetes Care. 2004 Mar;27(3):765-9. [14988299 ]
  8. 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. [15939423 ]

Enzymes

General function:
Involved in hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines
Specific function:
Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.
Gene Name:
DDAH1
Uniprot ID:
O94760
Molecular weight:
20189.135
Reactions
Asymmetric dimethylarginine + Water → Dimethylamine + Citrullinedetails
General function:
Involved in hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines
Specific function:
Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.
Gene Name:
DDAH2
Uniprot ID:
O95865
Molecular weight:
29643.54
Reactions
Asymmetric dimethylarginine + Water → Dimethylamine + Citrullinedetails
General function:
Involved in oxidoreductase activity
Specific function:
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.
Gene Name:
NOS2
Uniprot ID:
P35228
Molecular weight:
131116.3
References
  1. van Guldener C, Nanayakkara PW, Stehouwer CD: Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease. Clin Chem Lab Med. 2007;45(12):1683-7. [17937610 ]
General function:
Involved in oxidoreductase activity
Specific function:
Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.
Gene Name:
NOS3
Uniprot ID:
P29474
Molecular weight:
133273.59
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]