Nδ-Methylated L-arginine derivatives and their effects on the nitric oxide generating system

So far N-delta-methyl-L-arginine (MA) is only detected in yeast cells. Assuming that MA also exists in mammalians we examined possible physiological effects of N-delta-methylated L-arginine derivatives on the nitric oxide generating system, that is, nitric oxide synthase (NOS), arginase and dimethylarginine dimethylaminohydrolase (DDAH). N-delta-methyl-L-citrulline (MC) turned out to be a weak non-specific inhibitor of nitric oxide synthases. Moreover, MA is hydroxylated by all human NOS isoforms to N-hydroxy-N-delta-methyl-L-arginine (NHAM) but not converted further. This hydroxylated intermediate, however, was detected to be a potent inhibitor of bovine liver arginase with a K-i of 17.1 +/- 2.2 mu M. (C) 2007 Elsevier Ltd. All rights reserved.