L-Arginine regulates neuronal nitric oxide synthase production of superoxide and hydrogen peroxide

Pei Tsai, John Weaver, Guan Liang Cao, Sovitj Pou, Linda J. Roman, Anatoly A. Starkov, Gerald M. Rosen

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Tetrahydrobiopterin (H4B) in the absence of l-arginine has been shown to be an important factor in promoting the direct formation of hydrogen peroxide (H2O2) at the expense of superoxide (O 2.-) by neuronal nitric oxide synthase (NOS1) [Rosen GM, Tsai P, Weaver J, Porasuphatana S, Roman LJ, Starkov AA, et al. Role of tetrahydrobiopterin in the regulation of neuronal nitric-oxide synthase-generated superoxide. J Biol Chem 2002;277:40275-80]. Based on these findings, it is hypothesized that l-arginine also shifts the equilibrium between O2.- and H2O2. Experiments were designed to test this theory. As the concentration of l-arginine and N ω-hydroxyl-l-arginine increases, the rate of NADPH consumption for H4B-bound NOS1 decreased resulting in lower rates of both O 2.- and H2O2 generation, while increasing the rate of nitric oxide (.NO) production. At saturating concentrations of l-arginine or Nω-hydroxyl-l-arginine (50 μM), NOS1 still produced O2.- and H2O 2. Both L-arginine and Nω-hydroxyl-L-arginine have greater impact on the rate of generation of O2.- than on H2O2.

Original languageEnglish (US)
Pages (from-to)971-979
Number of pages9
JournalBiochemical Pharmacology
Issue number6
StatePublished - Mar 15 2005
Externally publishedYes


  • Hydrogen peroxide
  • L-Arginine
  • N-Hydroxyl-L-arginine
  • Neuronal nitric oxide synthase
  • Nitric oxide
  • superoxide

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology


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