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Bioorg Med Chem. 2008 Mar 1;16(5):2305-12. Epub 2007 Nov 29.

N(delta)-Methylated L-arginine derivatives and their effects on the nitric oxide generating system.

Author information

1
Department of Pharmaceutical Chemistry, Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Gutenbergstr. 76-78, D-24118 Kiel, Germany.

Abstract

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(omega)-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 microM.

PMID:
18083522
DOI:
10.1016/j.bmc.2007.11.066
[Indexed for MEDLINE]

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