| Record Information |
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| Version | 2.0 |
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| Creation Date | 2014-08-29 05:49:09 UTC |
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| Update Date | 2014-12-24 20:26:41 UTC |
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| Accession Number | T3D4171 |
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| Identification |
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| Common Name | Asymmetric dimethylarginine |
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| Class | Small Molecule |
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| Description | Asymmetric 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.
Asymmetric 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. |
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| Compound Type | - Amide
- Amine
- Enzyme Inhibitor
- Food Toxin
- Industrial/Workplace Toxin
- Metabolite
- Natural Compound
- Organic Compound
- Uremic Toxin
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| Chemical Structure | |
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| Synonyms | | Synonym | | 2-Amino-5-(amino-dimethylamino-methylidene)amino-pentanoate | | 2-Amino-5-(amino-dimethylamino-methylidene)amino-pentanoic acid | | ADMA | | Dimethyl-L-arginine | | Guanidino-n,n-dimethylarginine | | N(5)-((Dimethylamino)iminomethyl)-L-ornithine | | N(5)-[(dimethylamino)(imino)methyl]-L-ornithine | | N(g),N(g)-dimethyl-l-arginine | | N(g),N(g)-dimethylarginine | | N(g)-dimethylarginine | | N(G1),N(G1)-Dimethylarginine | | N(Omega),N(omega)-dimethyl-L-arginine | | NG,NG-Dimethyl-L-arginine | | NG,NG-dimethylarginine | | NG-dimethylarginine | | Nomega,Nomega'-Dimethyl-L-arginine |
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| Chemical Formula | C8H18N4O2 |
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| Average Molecular Mass | 202.254 g/mol |
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| Monoisotopic Mass | 202.143 g/mol |
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| CAS Registry Number | 30315-93-6 |
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| IUPAC Name | (2S)-2-amino-5-[(E)-[amino(dimethylamino)methylidene]amino]pentanoic acid |
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| Traditional Name | asymmetric dimethylarginine |
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| SMILES | [H][C@](N)(CCCNC(=N)N(C)C)C(O)=O |
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| 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 |
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| InChI Key | InChIKey=YDGMGEXADBMOMJ-LURJTMIESA-N |
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| Chemical Taxonomy |
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| 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. |
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| Kingdom | Organic compounds |
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| Super Class | Organic acids and derivatives |
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| Class | Carboxylic acids and derivatives |
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| Sub Class | Amino acids, peptides, and analogues |
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| Direct Parent | Arginine and derivatives |
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| Alternative Parents | |
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| Substituents | - Arginine or derivatives
- Alpha-amino acid
- L-alpha-amino acid
- Fatty acid
- Guanidine
- Amino acid
- Carboximidamide
- Monocarboxylic acid or derivatives
- Carboxylic acid
- Hydrocarbon derivative
- Organopnictogen compound
- Organic oxygen compound
- Primary amine
- Organooxygen compound
- Organonitrogen compound
- Primary aliphatic amine
- Imine
- Carbonyl group
- Amine
- Organic nitrogen compound
- Organic oxide
- Aliphatic acyclic compound
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| Molecular Framework | Aliphatic acyclic compounds |
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| External Descriptors | |
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| Biological Properties |
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| Status | Detected and Not Quantified |
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| Origin | Endogenous |
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| Cellular Locations | |
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| Biofluid Locations | Not Available |
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| Tissue Locations | |
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| Pathways | Not Available |
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| Applications | Not Available |
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| Biological Roles | |
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| Chemical Roles | |
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| Physical Properties |
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| State | Solid |
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| Appearance | White powder. |
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| Experimental Properties | | Property | Value |
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| Melting Point | 195 - 197°C | | Boiling Point | Not Available | | Solubility | Not Available | | LogP | Not Available |
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| Predicted Properties | |
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| Spectra |
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| Spectra | | Spectrum Type | Description | Splash Key | Deposition Date | View |
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| GC-MS | GC-MS Spectrum - GC-EI-TOF (Non-derivatized) | splash10-0f6w-1920000000-352e317361bed495b71b | 2017-09-12 | View Spectrum | | GC-MS | GC-MS Spectrum - GC-EI-TOF (Non-derivatized) | splash10-0f6w-1920000000-352e317361bed495b71b | 2018-05-18 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | splash10-00dl-9300000000-4fc2a444d078a1eb4d85 | 2016-09-22 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive | splash10-00dl-9520000000-928759e33b3f9821da4a | 2017-10-06 | 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 - 35V, Negative | splash10-0006-9100000000-2849c1945541be90da8a | 2021-09-20 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 35V, Positive | splash10-00di-9200000000-f7af59f4a85b35ee2239 | 2021-09-20 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - 35V, Positive | splash10-00di-9310000000-901ceea58124eb646d2d | 2021-09-20 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-0pbi-1930000000-6a12bc30dbe08d316d09 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-0abi-8900000000-47e0a5a868dce918c9b7 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-00di-9000000000-d674ec18daa47f080be4 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-0udi-3390000000-2b624585e91010265a57 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-0f79-9420000000-b8fe15104f41182b9d9b | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-00dl-9100000000-120212bd5d151152c8ad | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-0uk9-9370000000-4bea91f4d0256a94739f | 2021-09-22 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-01si-2900000000-8fc254a7c96b0565c1ff | 2021-09-22 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-0006-9200000000-428e5ae3fbdfa34b338c | 2021-09-22 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-0udr-2690000000-5766392f870c77d53359 | 2021-09-22 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-00dr-9200000000-a7b438425f1f49a1a48b | 2021-09-22 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-00di-9000000000-e6f7e053fa2072aa45ff | 2021-09-22 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, 100 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 13C NMR Spectrum (1D, 100 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, 1000 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 13C NMR Spectrum (1D, 1000 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, 200 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 13C NMR Spectrum (1D, 200 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, 300 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 13C NMR Spectrum (1D, 300 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, 400 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 13C NMR Spectrum (1D, 400 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, 500 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 13C NMR Spectrum (1D, 500 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, 600 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 13C NMR Spectrum (1D, 600 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, 700 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 13C NMR Spectrum (1D, 700 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, 800 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 13C NMR Spectrum (1D, 800 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, 900 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum | | 1D NMR | 13C NMR Spectrum (1D, 900 MHz, D2O, predicted) | Not Available | 2021-09-25 | View Spectrum |
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| Toxicity Profile |
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| Route of Exposure | Endogenous, Ingestion, Dermal (contact) |
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| Mechanism of Toxicity | Uremic toxins such as asymmetric 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) (2). 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 (3). |
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| 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. |
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| Toxicity Values | Not Available |
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| Lethal Dose | Not Available |
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| Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). |
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| Uses/Sources | Naturally produced by the body (endogenous). |
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| Minimum Risk Level | Not Available |
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| Health Effects | Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. |
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| 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. |
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| Treatment | Kidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored. |
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| Normal Concentrations |
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| Not Available |
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| Abnormal Concentrations |
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| Not Available |
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| External Links |
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| DrugBank ID | DB01686 |
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| HMDB ID | HMDB01539 |
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| PubChem Compound ID | 123831 |
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| ChEMBL ID | CHEMBL457530 |
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| ChemSpider ID | 110375 |
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| KEGG ID | C03626 |
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| UniProt ID | Not Available |
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| OMIM ID | |
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| ChEBI ID | 17929 |
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| BioCyc ID | CPD-596 |
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| CTD ID | Not Available |
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| Stitch ID | Not Available |
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| PDB ID | DA2 |
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| ACToR ID | Not Available |
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| Wikipedia Link | Asymmetric dimethylarginine |
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| References |
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| Synthesis Reference | Not Available |
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| MSDS | Link |
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| General References | - 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
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| Gene Regulation |
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| Up-Regulated Genes | Not Available |
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| Down-Regulated Genes | Not Available |
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