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 H ₂O₂ 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.