Fig. (1).

Overview of pathways of synthesis and metabolism of ADMA. Methylation of arginine residues within peptides occurs through N-methyltransferases, protein arginine N-methyltransferase-1 (PRMT-1). S-adenosylmethionine (SAM) is the methyl donor, changing to S-adenosylhomocysteine (SAH). Proteolytic breakdown of the proteins leads to the generation of ADMA and N-monomethyl-L-arginine (L-NMMA) within cells, and is detectable in the circulation. ADMA is an inhibitor of endothelial nitric oxide synthase (eNOS) by competing with its substrate L-arginine thus impairing nitric oxide (NO) production, thus leading to endothelial dysfunction and subsequently atherosclerosis. ADMA is eliminated partly via urinary excretion but mainly via metabolism by the enzyme dimethylarginine dimethylaminohydrolase (DDAH) to citrulline and dimethylamine.