The current perspective holds that the generation of secondary signaling mediators from nitrite (NO₂⁻) requires acidification to nitrous acid (HNO₂) or metal catalysis. Herein, the use of stable isotope–labeled NO₂⁻ and LC-MS/MS analysis of products reveals that NO₂⁻ also participates in fatty acid nitration and thiol S-nitrosation at neutral pH. These reactions occur in the absence of metal centers and are stimulated by autoxidation of nitric oxide (^•NO) via the formation of symmetrical dinitrogen trioxide (nitrous anhydride, symN₂O₃). Although theoretical models have predicted physiological symN₂O₃ formation, its generation is now demonstrated in aqueous reaction systems, cell models and in vivo, with the concerted reactions of ^•NO and NO₂⁻ shown to be critical for symN₂O₃ formation. These results reveal new mechanisms underlying the NO₂⁻ propagation of ^•NO signaling and the regulation of both biomolecule function and signaling network activity via NO₂⁻-dependent nitrosation and nitration reactions.

目前的观点认为，从亚硝酸盐 (NO ₂ ^- )产生二级信号介质需要酸化为亚硝酸 (HNO ₂ ) 或金属催化。在此，使用稳定同位素标记的 NO ₂ ^-和 LC-MS/MS 分析产品表明，NO ₂ ^-在中性 pH 值下也参与脂肪酸硝化和硫醇 S-亚硝化。这些反应在没有金属中心的情况下发生，并且通过形成对称的三氧化二氮（亚硝酸酐，sym N ₂ O ₃）而受到一氧化氮 ( ^• NO)的自动氧化的刺激。虽然理论模型已经预测了生理sym N ₂ O _{3 的}形成，现在已在水性反应系统、细胞模型和体内证明其生成，其中^• NO 和 NO ₂ ^-的协同反应对sym N ₂ O _{3 的}形成至关重要。这些结果揭示了 NO ₂ ^-传播的新机制^• NO 信号传导以及通过 NO ₂ ^-依赖的亚硝化和硝化反应调节生物分子功能和信号网络活动。