A comparative study of neuronal and inducible nitric oxide synthases: Generation of nitric oxide, superoxide, and hydrogen peroxide

Nitric oxide synthases (NOS) independent of the isozyme, produce nitric oxide (NO), superoxide (O2−), and hydrogen peroxide (H2O2). Since NO has been implicated in many physiological processes, the importance of O2− and H2O2 in regulating cell signaling by NO cannot be overlooked. Before addressing these questions, we investigated the production of NO, O2−, and H2O2 by purified NOS. NOS 1 and NOS 2 were chosen, as the flux of NO from each isozyme supports differential biological activity. We found that the initial rate and sustained production of NO was considerably greater for NOS 2 as compared to NOS 1. In the absence of l-arginine, however, NOS 1 generation of O2− and H2O2 was found to be substantially greater than that measured for NOS 2. Differences between NOS 1 and NOS 2 production of NO, O2−, and H2O2 may define the specific physiologic function of each isozyme.