Fig. 1

Metabolism of nitric oxide. Nitric oxide (NO) is synthesized from L-arginine. This reaction is catalyzed by nitric oxide synthases (NOS). Protein synthesis incorporates L-arginine into proteins. Protein-bound L-arginine is methylated by protein methyltransferases (PRMT) and lysed to the metabolites asymmetric and symmetric dimethylarginine (ADMA, SDMA). ADMA is mainly metabolized to citrulline and dimethylamine via dimethylarginine dimethylaminohydrolase (DDAH). A small fraction of ADMA and almost the entire amount of SDMA are renally eliminated. ADMA inhibits the NOS competitively and SDMA interferes with L-arginine transport. Arginase reduces the bioavailability of L-arginine by degrading it to L-ornithine and urea. Nitric oxide has a negative feedback mechanism to DDAH, which leads to less metabolism of ADMA