Asymmetric dimethylarginine

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Structural formula
Structure of asymmetric dimethylarginine
General
Surname asymmetric dimethylarginine
other names
  • N , N -dimethylarginine
  • N , N -dimethyl- L- arginine
  • Guanidine- N , N -dimethylarginine
Molecular formula C 8 H 18 N 4 O 2
External identifiers / databases
CAS number 30315-93-6
PubChem 123831
ChemSpider 110375
DrugBank DB01686
Wikidata Q752685
properties
Molar mass 202.25 g mol −1
Physical state

firmly

safety instructions
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Asymmetrical dimethylarginine ( ADMA ) is a methylated derivative of the amino acid L - arginine , which can be found in the blood plasma of the human organism. It is produced by protein methyl transferases (PRMTs), which methylate arginine bound in proteins . These methylarginines are released through proteolysis . The methylated arginine derivatives such as ADMA are broken down by dimethylarginine dimethylaminohydrolases (DDAHs). ADMA is considered a risk marker and a. for arteriosclerosis . In veterinary medicine, symmetrical dimethylarginine is used as a marker for kidney function.

Medical importance

Elevated levels of ADMA are found in people with high blood pressure , elevated cholesterol , diabetes mellitus, and chronic kidney disease . There is a close relationship between levels of ADMA in blood plasma and the thickness of the media and intima of the common carotid artery , one of the surrogate markers of atherosclerosis in the general population. Elevated ADMA levels are a strong risk factor for developing cardiovascular complications such as heart disease in people with coronary artery disease , diabetes, and chronic kidney disease . B. heart attack or stroke .

Elevated ADMA levels may lead to inactivation of nitric oxide , which normally relaxes the vascular smooth muscles , which in turn leads to vasodilation and thus to a lowering of the afterload on the heart and blood pressure . ADMA could thus promote the development of arteriosclerosis by lowering the nitric oxide level on the endothelial cells of the vessel wall . The exact molecular mechanism that leads to an increase in ADMA in the blood is still unknown (as of 2014). However, increased oxidative and nitrosative stress and associated metabolic disorders such as increased homocysteine ​​levels are increasingly being held responsible for this. ADMA is the endogenous antagonist of L-arginine , the substrate for nitric oxide formation, and thus a decisive disease and mortality factor, which can cause dangerous nitrosative and oxidative stress by decoupling the synthesis of nitric oxide and the consumption of this radical scavenger.

Measurement methods and reference range

The determination of ADMA is carried out in the analytical or clinical laboratory with the help of HPLC , an ELISA or mass spectrometry . In the blood of a healthy person, an average concentration of 0.7 µmol / l (micromol per liter) is the norm.

swell

  1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  2. ↑ Matsuguma, K. et al. (2006): Molecular Mechanism for Elevation of Asymmetric Dimethylarginine and Its Role for Hypertension in Chronic Kidney Disease. In: J Am Soc Nephrol . 17, 2176-2183. PMID 16807406 doi : 10.1681 / ASN.2005121379
  3. ↑ Boger, RH et al .: Asymmetric dimethylarginine (ADMA) as a prospective marker of cardiovascular disease and mortality - an update on patient populations with a wide range of cardiovascular risk. Pharmacol Res , 2009. 60 (6): p. 481-7.
  4. ↑ Sibal, L. et al .: The role of asymmetric dimethylarginine (ADMA) in endothelial dysfunction and cardiovascular disease. Current cardiology reviews , 2010. 6 (2): p. 82.
  5. ↑ I. Seljeflot, BB Nilsson, AS West helmet, V. Bratseth, H. Arnesen: The L-arginine-asymmetric dimethylarginine ratio is strongly related to the severity of chronic heart failure. No effects of exercise training. In: J Card Fail 2011 , Volume 17 (2): pp. 135–142, doi : 10.1016 / j.cardfail.2010.09.003 . PIMD 21300303
  6. ↑ Seljeflot I., BB Nilsson, AS West Home, V. Bratseth, H. Arnesen: The L-arginine-asymmetric dimethylarginine ratio is strongly related to the severity of chronic heart failure. No effects of exercise training. In: J. Cardiac. Fail. Volume 17, 2011, pp. 135-142.
  7. ↑ M. Anderssohn, M. Rosenberg, E. Schwedhelm, C. Zugck, M. Lutz, N. Lüneburg, N. Frey, RH Böger: The L-Arginine-asymmetric dimethylarginine ratio is an independent predictor of mortality in dilated cardiomyopathy. In: J. Card. Fail . Volume 18, No. 12, 2012, pp. 904-911.
  8. ^ Pizzarelli, R. Maas, P. Dattolo, G. Tripepi, S. Michelassi, G. D'Arrigo, M. Mieth, S. Bandinelli, L. Ferrucci, C. Zoccali: Asymmetric dimethylarginine predicts survival in the elderly. In: Age , Volume 35, No. 6, 2013, pp. 2465-2475.
  9. ↑ SM Bode-Böger, J. Muke, A. Surdacki, G. Brabant, RH Böger, JC Frölich: Oral L-arginine improves endothelial function in healthy individuals older than 70 years. In: Vasc. Med . Volume 8, 2003, pp. 77-81.
  10. ↑ K. Jung, O. Petrowicz: L-arginine and folic acid in arteriosclerosis. Results of a prospective, multicenter consumption study. In: Perfusion , Volume 21, 2008, pp. 148-156.
  11. ↑ K. Sydow, RH Böger: Reloaded: ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst (e) inemia: effects of L-arginine and B vitamins. In: Cardiovasc. Res. , 2012, doi : 10.1093 / cvr / cvs205 .
  12. ↑ Tain Y.-L., Huang L.-T. (2014) Restoration of asymmetric dimethylarginine-nitric oxide balance to prevent the development of hypertension. Int. J. Mol. Sci. 15, 11773-11782

literature

  • Vallance, P. et al. (1992): Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. In: Lancet. 339: 572-575 (8793). PMID 1347093