Metabolism of asymmetric dimethylarginine and its clinical significance

Asymmetric dimethylarginine is an endogenous inhibitory of nitric oxide synthase enzyme. Nitric oxide has regulatory functions such as endothelial dependent vasodilatation, smooth muscle proliferation in vessel wall, cell-cell interactions, platelet aggregation and adhesion inhibition and monosit adhesion inhibition. Asymmetric dimethylarginine, a modified form of arginine amino acid, is produced by proteolysis of methylated proteins. Net amount of produced and released ADMA depends on the balance between arginine methylation, degradation of proteins containing methylated arginine and metabolism by the enzyme dimetilarjinin dimethylaminohydrolase and the excretion rates. Almost all of the asymmetric dimetilarjininin produced in cell is digested by the dimetilarjinin dimethylaminohydrolase enzyme, a small amounts of the asymmetric dimetilarjinin is moved from the cells into the bloodstream by cationic amino acid transporters. Asymmetric dimetilarjinin in plasma either excreted by urine without change, or take back into the cell primarily at kidneys and liver and is metabolized by the enzyme dimetilarjinin dimethylaminohydrolase. Plasma levels of asymmetric dimetilarjinin can be measured by highperformance liquid chromatography, mass spectrometry and ELISA with various advantages and disadvantages. It is not known that asymmetric dimetilarjinin in plasma biologically active or not, but in literature, there are many studies reporting high plasma asymmetric dimethylarginine levels in various clinical situations. Clinical and experimental studies, performed in our department, also showed that elevated plasma levels of asymmetric dimethylarginine in chronic kidney disease, hypertension, endometriosis, and schizophrenia in accordance with the literature. Nowadays it is considered as a new cardiovascular risk factor due to its inhibition the synthesis of nitric oxide which has many regulatory effects on cardiovascular system. Leading to endothelial dysfunction and the importance of endothelial dysfunction in pathogenesis of many diseases, indicates that the research about asymmetric dimethylarginine will continue in the near future too.