L-arginine analogs as alternate substrates for nitric oxide synthase.
The L-arginine analogs, N(delta)-methyl-L-arginine (deltaMA) and L-canavanine, were used to probe the role of the N delta nitrogen of L-arginine in the reaction catalyzed by nitric oxide synthase (NOS). deltaMA was synthesized and found to be a partial alternate substrate and a weak, reversible inhibitor of NOS with a Ki equal to 1.4 mM. deltaMA undergoes hydroxylation; however, it is not converted further, hence it functions as a partial substrate. L-Canavanine was converted to an L-homoserine presumably via initial hydroxylation and decomposition. The mechanism of this reaction and products of this reaction were not probed further.
Department of Chemistry, University of California, Berkeley, CA 94720-1460, USA.
Scott D
SD
Luzzi
Michael A
MA
Marletta
D001120:Arginine / Q000031:analogs & derivatives*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D001120:Arginine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II