-

Öz

Asymmetric dimethyl arginine (ADMA) is an endogenous inhibitor of Nitric Oxide Synthase (NOS) enzyme. Methylated arginine has been found in human urine for the first time in the 1970s. However the first study with ADMA has been made among patients with chronic renal failure in 1992. It has been reported by many studies that ADMA contributed in endothelial dysfunction and atherosclerosis and can be used as a marker in recent years. ADMA was found to be elevated in the serum in cases of renal insufficiency, atherosclerosis, hyperglycemia and in hyperhomocysteinemia. In this review we will study ADMA structure, synthesis, metabolism and its relationship with clinical conditions

Anahtar Kelimeler

• Asymmetric dimethyl arginine, nitric oxide

Asimetrik Dimetil Arjinin (ADMA) Metabolizması

Öz

Asimetrik dimetil arjinin (ADMA) endojen Nitrik Oksit Sentaz enzimi (NOS) inhibitörüdür. İlk kez 1970 yıllarında metillenmiş arjininler insan idrarında saptanmıştır. Ancak ADMA ile ilgili ilk çalışma 1992’de Vallance ve arkadaşları tarafından kronik böbrek yetmezliği hastalarında yapılmıştır. Son yıllarda yapılan çok sayıda çalışmada ADMA’nın endotel disfonksiyonu ve atherosklerozda rol aldığı ve belirteç olarak kullanılabileceği bildirilmiştir. ADMA’nın ayrıca, böbrek yetmezliği, ateroskleroz, hiperglisemi, hiperhomosisteinemi durumlarında da serumda yükseldiği tespit edilmiştir. Biz bu derlemede ADMA’nın yapısı, sentezi, metabolizması ve klinik durumlar ile ilşkisini inceleyeceğiz.

Anahtar Kelimeler

• Asimetrik dimetil arjinin
• nitrik oksit
• ADMA

Kaynakça

1. Cekmen MB, Turgut M, Turkoz Y, et al. Nitric Oxide and Nitric Oxide Synthaze Physiologic and Pathologic Characterictics. T Klin J Ped. 2001;10(4):226-35.
2. Moncada S, Palmer RMJ, Higgs EA. Biosynthesis of nitric oxide from L-arginin: A pathway for the regülation of cell function and communication. Biochem Pharmacol 1989;38(11):1709-15.
3. Raghavan SA, Dikshit M. Vascular regulation by the L- arginine metabolites, nitric oxide and agmatine. Pharmacol Res. 2004;49(5):397-414.
4. Anggard E. Nitric Oxide: Mediator, murderer and medicine. The Lancet 1994; 343(8907):1199-206
5. Gritti P, Lanterna LA, Re M, et al. The use of inhaled nitric oxide and prone position in an ARDS patient with severe traumatic brain injury during spine stabilization. J Anesth 2012; DOI: 10.1007/s00540-012-1495-2 [Epub ahead of print].
6. Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb. Vasc Biol 2000;20(9):2032-7.
7. Vallance P, Leone A, Calver A, et al. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet. 1992;339(8793):572-5. 8. Valkonen V-P, Laaksonen R. Asymmetric dimethylarginine (ADMA) and acute vascular events. Clin Chim Acta: 2004;348(1-2):9-17.
8. Tarnow L, Hovind P, Teerlink T, et al. Elevated plasma ADMA as a marker of cardiovascular morbidity in early diabetic nephropathy in Type 1 diabetes. Diabetes Care 2004;27(3):765-9.

9. Hu T, Chouinard M, Cox Amy L, et al. X receptor agonist reduces serum asymmetric dimethylarginine levels through hepatic dimethylarginine
10. dimethylaminohydrolase-1 gene regulation. J Biol
11. Chem, 2006;281(52):39831-8.
12. Mittermayer F, Pleiner J, Krzyzanowska K, et al. Regular physical exercise normalizes elevated ADMA concentrations in patients with Type 1 Diabetes mellitus. Wien Klin Wochenschr. 2005;117(23-24):816- 20.
13. Beltowski J, Kedra A. Asymmetric dimethylarginine (ADMA) as a target for pharmacotherapy. Pharmacol Rep. 2006;58(2):159-78.
14. Nijveldt RJ, Siroen MPC, Teerlink T, Leeuwen MV. Elimination of Asymmetric Dimethylarginine by the Kidney and the Liver: A Link to the development of multiple organ failure. J. Nutr. 2004;134 (Supl. 10):2848S-52S.
15. Böger RH, Maas R, Schulze F, Schwedhelm E. Elevated levels of ADMA as a marker of cardiovascular disease and mortality. Clin Chem Lab Med. 2005;43(10):1124-9
16. Wang J, Sim AS, Wang XL, et al. Relations between plasma asymmetric dimethylarginine (ADMA) and risk factors for coronary disease.
17. Atherosclerosis. 2006;184(2):383-8.
18. Valkonen VP, Tuomainen TP, Laaksonen R. DDAH gene and
19. cardiovascular risk. Vasc Med.
20. 2005;10(Suppl.1):45-8.
21. Nijveldt JR, Leeuwen VP, Van Coen G, et al. Net renal extraction of ADMA and SDMA in fasting humans. Nephrol Dial Transplant 2002;17(11):1999-2002
22. Kielstein JT, Böger RH, Bode-Böger SM, et al.
23. Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: relationship to treatment method and atherosclerotic disease. J Am Soc Nephrol 1999;10(3):594-600. 19. Carmine Z, Francesca M, Tripepi G. novel cardiovascular risk factos in end stage renal disease. J Am Soc Nephrol. 2004;15(Suppl.1):S77-80.
24. Selcoki Y, Aydın M, İkizek M, et al. Association
25. Between Asymmetric Dimethylarginine and the Severity of Coronary Artery Disease in Patients with Chronic Kidney Disease. Turk Neph Dial Transpl 2011;20(1):58-64
26. Şahin M, Arslan Ç, Naziroğlu M, et al. Asymmetric
27. dimethylarginine and Nitric Oxide Levels as a Sign of endothelial disfunction in Behçet’s Disease. Ann. of Clinical & Lab. Science. 2006;36(4):449-54
28. Aydın M, Koca C, Uysal S, et al. Serum nitric oxide,
29. asymmetric dimethylarginine and homocysteine levels in active Behcet's disease Turk J Med Sci 2012; 42(Sup.1): 1194-9
30. Chan NN, Chan JCN. Asymmetric dimethylarginine (ADMA): a potential link between endothelial
31. dysfunction and cardiovascular diseases in insulin resistance syndrome? Diabetologia. 2002;45(12):1609–16.
32. Böger RH. ADMA, an endogenous ınhibitor of nitric
33. oxide synthase, explains the ‘L-arginine paradox and acts as a novel cardiovascular risk factor. J Nutr. 2004;134(10 suppl):2842S-47S.
34. Richter B, Niessner A, Penka M, et al. Endurance training reduces circulating ADMA and MPO levels in persons at risk of coronary events. Thromb Haemost. 2005;94(6):1306-11.
35. Sydow K, Schwedhelm E, Arakawa N, et al. ADMA and oxidative stres are responsible for endothelial dysfunction in hyperhomocysteinemia: effects of L- arginine and B vitamins. Cardiovasc Res. 2003;57(1):244-52
36. Arlt S, Schwedhelm E, Kölsch H, et al.
37. Dimethylarginines, homocysteine metabolism, and cerebrospinal fluid markers for Alzheimer's disease. J Alzheimers Dis 2012;31(4):751-8.
38. Batista M, Landim P, Filho AC, Chagas ACP. Asymmetric Dimethylarginine (ADMA) and Endothelial Dysfunction: Implications for Atherogenesis. Clinics. 2009;64(5):471–8.
39. Scalera F, Borlak J, Beckmann B, et al. Endogenous nitric oxide synthesis inhibitor asymmetric dimethyl L- arginine accelerates endothelial cell senescence. Arterioscler Thromb Vasc Biol 2004;24(10):1816-22.