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

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Tetrahydrobiopterin (H 4B) in the absence of l-arginine has been shown to be an important factor in promoting the direct formation of hydrogen peroxide (H 2O 2) 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 O 2 − and H 2O 2. 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 H 4B-bound NOS1 decreased resulting in lower rates of both O 2 − and H 2O 2 generation, while increasing the rate of nitric oxide ( NO) production. At saturating concentrations of l-arginine or N ω-hydroxyl- l-arginine (50 μM), NOS1 still produced O 2 − and H 2O 2. Both l-arginine and N ω-hydroxyl- l-arginine have greater impact on the rate of generation of O 2 − than on H 2O 2.