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.
- Hydrogen peroxide
- Neuronal nitric oxide synthase
- Nitric oxide
ASJC Scopus subject areas