SCIENCE@home

Inhibitors of brain nitric oxide synthase. Binding kinetics, metabolism, and enzyme inactivation.

Peter Klatt,Kurt Schmidt,Friedrich Brunner,Bernd Mayer

Published 1994 in Journal of Biological Chemistry

ABSTRACT

Nitric oxide (NO) is synthesized from L-arginine by different NO synthase isozymes, which are inhibited by the substrate analogs NG-methyl- and NG-nitro-L-arginine. We studied binding of 3H-labeled NG-nitro-L-arginine to purified brain NO synthase and compared the data with results obtained in enzyme kinetic experiments. Binding data revealed a single binding site for NG-nitro-L-[3H]arginine (KD = 0.17 microM). Binding was competitively antagonized by L-arginine (KI = 2.9 microM). The half-time of dissociation was remarkably slow (9.4 min) and closely correlated with the time necessary for surmounting NO synthase inhibition by dilution. Although an apparently less potent inhibitor, NG-methyl-L-arginine exhibited the same affinity for brain NO synthase as the nitro derivative (KI = 0.17 microM), and in initial rate experiments, almost equal KI values were obtained for NG-methyl-L-arginine (0.61 microM) and NG-nitro-L-arginine (0.53 microM). However, after prolonged incubation periods, NG-nitro-L-arginine induced a rapid inactivation of the enzyme, whereas the methyl derivative turned out to be a substrate of NO synthase, which was slowly converted into stoichiometric amounts of NO and L-citrulline.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-47 of 47 references · Page 1 of 1

CITED BY

Showing 1-100 of 193 citing papers · Page 1 of 2

12
Next