title: L-arginine regulates neuronal nitric oxide synthase production of superoxide and hydrogen peroxide.
abstract: 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).
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Tsai
authors.forename: John
authors.initials: J
authors.lastname: Weaver
authors.forename: Guan Liang
authors.initials: GL
authors.lastname: Cao
authors.forename: Sovitj
authors.initials: S
authors.lastname: Pou
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Roman
authors.forename: Anatoly A
authors.initials: AA
authors.lastname: Starkov
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Rosen
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D013481:Superoxides / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D013481:Superoxides; D001120:Arginine; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat