Tsai Pei, Weaver John, Cao Guan Liang, Pou Sovitj, Roman Linda J, Starkov Anatoly A, Rosen Gerald M
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
Biochem Pharmacol. 2005 Mar 15;69(6):971-9. doi: 10.1016/j.bcp.2004.12.009. Epub 2005 Jan 28.
Tetrahydrobiopterin (H(4)B) in the absence of L-arginine has been shown to be an important factor in promoting the direct formation of hydrogen peroxide (H(2)O(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(2)O(2). Experiments were designed to test this theory. As the concentration of L-arginine and N(omega)-hydroxyl-L-arginine increases, the rate of NADPH consumption for H(4)B-bound NOS1 decreased resulting in lower rates of both O(2)(-) and H(2)O(2) generation, while increasing the rate of nitric oxide (NO) production. At saturating concentrations of L-arginine or N(omega)-hydroxyl-L-arginine (50microM), NOS1 still produced O(2)(-) and H(2)O(2). Both L-arginine and N(omega)-hydroxyl-L-arginine have greater impact on the rate of generation of O(2)(-) than on H(2)O(2).
