Brain nitric oxide synthase is a Ca2+/calmodulin-regulated enzyme which converts L-arginine into NO. Enzymatic activity of this enzyme essentially depends on NADPH and is stimulated by tetrahydrobiopterin (H4biopterin). We found that purified NO synthase contains enzyme-bound H4 biopterin, explaining the enzymatic activity observed in the absence of added cofactor. Together with the finding that H4 biopterin was effective at substoichiometrical concentrations, these results indicate that NO synthase essentially depends on H4 biopterin as a cofactor which is recycled during enzymatic NO formation. We found that the purified enzyme also contains FAD, FMN and non-heme iron in equimolar amounts and exhibits striking activities, including a Ca2+/calmodulin-dependent NADPH oxidase activity, leading to the formation of hydrogen peroxide at suboptimal concentrations of L-arginine or H4 biopterin. © 1991.
Mayer, B., John, M., Heinzel, B., Werner, E. R., Wachter, H., Schultz, G., & Böhme, E. (1991). Brain nitric oxide synthase is a biopterin- and flavin-containing multi-functional oxido-reductase. FEBS Letters, 288(1–2), 187–191. https://doi.org/10.1016/0014-5793(91)81031-3