Figure 7.

Modified hypothesis on the NOS reaction mechanism and interaction of NOS reaction products. In the absence of H₄Bip, uncoupled NADPH consumption and O₂ activation appears to yield primarily H₂O₂, not O_2⨪. Thus, analytical limitations cannot explain the absence of a ·NO signal from NOS-catalyzed Arg turnover under these conditions. SOD converts a proximal NOS product, the ·NO precursor (NO_pre), to ·NO. Candidate molecules for NO_pre include NH₂O· and NO⁻, yielding N₂O and NH₂OH as by-products. Generated ONOO⁻ (e.g., from H₄Bip-derived O_2⨪ + ·NO or O₂ + ·NO⁻) will, in a secondary reaction, consume additional NADPH equivalents. ONOO⁻ can be scavenged by high thiol concentrations, providing an alternative source for RSNO, and yield not only NO₃⁻ but also NO₂⁻. ▴ depicts requirement for redox equivalents (NADPH, SOD, and possibly also H₄Bip).