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

So far Nδ-methyl-l-arginine (MA) is only detected in yeast cells. Assuming that MA also exists in mammalians we examined possible physiological effects of Nδ-methylated l-arginine derivatives on the nitric oxide generating system, that is, nitric oxide synthase (NOS), arginase and dimethylarginine dimethylaminohydrolase (DDAH). Nδ-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 Nω-hydroxy-Nδ-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 Ki of 17.1 ± 2.2 μM.

The influence of Nδ-methyl-l-arginine and its presumed metabolites by NOS catalysis was investigated on the whole nitric oxide generating system including NOSs, arginase and DDAH. Nω-Hydroxy-Nδ-methyl-l-arginine presents a strong inhibitor of arginase with a Ki of 17 μM.Figure optionsDownload as PowerPoint slide