The role of tetrahydrobiopterin in the regulation of neuronal nitric-oxide synthase-generated superoxide

Gerald M. Rosen, Pei Tsai, John Weaver, Supatra Porasuphatana, Linda J. Roman, Anatoly A. Starkov, Gary Fiskum, Sovitj Pou

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

Tetrahydrobiopterin (H4B) is a critical element in the nitric-oxide synthase (NOS) metabolism of L-arginine to L-citrulline and NO.. It has been hypothesized that in the absence of or under nonsaturating levels of L-arginine where O2 reduction is the primary outcome of NOS activation, H4B promotes the generation of H2O2 at the expense of O2._. The experiments were designed to test this hypothesis. To test this theory, two different enzyme preparations, H4B-bound NOS I and H4B-free NOS I, were used. Initial rates of NADPH turnover and O2 utilization were found to be considerably greater in the H4B-bound NOS I preparation than in the H4B-free NOS I preparation. In contrast, the initial generation of O2.- from the H4B-free NOS I preparation was found to be substantially greater than that measured using the H4B-bound NOS I preparation. Finally, by spin trapping nearly all of the NOS I produced O2.-, we found that the initial rate of H2O2 production by H4B-bound NOS I was considerably greater than that for H4B-free NOS I.

Original languageEnglish (US)
Pages (from-to)40275-40280
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number43
DOIs
StatePublished - Oct 25 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Rosen, G. M., Tsai, P., Weaver, J., Porasuphatana, S., Roman, L. J., Starkov, A. A., Fiskum, G., & Pou, S. (2002). The role of tetrahydrobiopterin in the regulation of neuronal nitric-oxide synthase-generated superoxide. Journal of Biological Chemistry, 277(43), 40275-40280. https://doi.org/10.1074/jbc.M200853200