N(delta)-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(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.
Kotthaus
Jürke
J
Department of Pharmaceutical Chemistry, Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Gutenbergstr. 76-78, D-24118 Kiel, Germany.
Schade
Dennis
D
Töpker-Lehmann
Katrin
K
Beitz
Eric
E
Clement
Bernd
B
D000818:Animals; D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D008862:Microsomes, Liver / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D015394:Molecular Structure; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010084:Oxidation-Reduction; D013552:Swine
D009569:Nitric Oxide; C027742:delta-N-methylarginine; D003577:Cytochrome P-450 Enzyme System; D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase