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

Abstract

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