L-arginine regulates neuronal nitric oxide synthase production of superoxide and hydrogen peroxide.
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).
Tsai
Pei
P
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
Weaver
John
J
Cao
Guan Liang
GL
Pou
Sovitj
S
Roman
Linda J
LJ
Starkov
Anatoly A
AA
Rosen
Gerald M
GM
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*
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