The role of tetrahydrobiopterin in the regulation of neuronal nitric-oxide synthase-generated superoxide Academic Article uri icon


MeSH Major

  • Biopterin
  • Nitric Oxide Synthase
  • Superoxides


  • Tetrahydrobiopterin (H(4)B) 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 O(2) reduction is the primary outcome of NOS activation, H(4)B promotes the generation of H(2)O(2) at the expense of O(2)(-.). The experiments were designed to test this hypothesis. To test this theory, two different enzyme preparations, H(4)B-bound NOS I and H(4)B-free NOS I, were used. Initial rates of NADPH turnover and O(2) utilization were found to be considerably greater in the H(4)B-bound NOS I preparation than in the H(4)B-free NOS I preparation. In contrast, the initial generation of O(2)(-.) from the H(4)B-free NOS I preparation was found to be substantially greater than that measured using the H(4)B-bound NOS I preparation. Finally, by spin trapping nearly all of the NOS I produced O(2)(-.), we found that the initial rate of H(2)O(2) production by H(4)B-bound NOS I was considerably greater than that for H(4)B-free NOS I.

publication date

  • October 25, 2002



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1074/jbc.M200853200

PubMed ID

  • 12183447

Additional Document Info

start page

  • 40275

end page

  • 80


  • 277


  • 43