Effect of Keto Acids on Asymmetric Dimethylarginine, Muscle, and Fat Tissue in Chronic Kidney Disease and After Kidney Transplantation

Abstract

ASYMMETRIC DIMETHYLARGININE (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase. By competitively displacing L-arginine from the substrate-binding site of NO synthase, ADMA interferes with many physiological functions of NO, such as endothelium-dependent vasodilatation and leukocyte adhesion. Asymmetric dimethylarginine and its biologically inactive regioisomer, symmetric dimethylarginine (SDMA), can be found in human plasma and urine in low concentrations. Concentrations of both dimethylarginines are increased in patients with end-stage renal disease, which may explain, at least in part, the endothelial dysfunction and cardiovascular complications in this patient population. In addition, the metabolism of ADMA, but not of SDMA, occurs via hydrolytic degradation to citrulline and dimethylamine by the enzyme dimethylarginine dimethylaminohydrolase (DDAH).