Peroxynitrite

Peroxynitrite (ONOO−) is a reactive nitrogen species formed when nitric oxide (NO•) rapidly combines with the superoxide radical (O2•−). As a short-lived oxidant and nitrating agent, it participates in cellular signaling at low concentrations and oxidative/nitrosative damage at higher levels. In biological contexts, peroxynitrite is often described as a mediator of nitrosative stress.

Formation occurs wherever NO• and O2•− are produced in proximity, such as activated macrophages, endothelial cells, and neurons. The reaction is diffusion-controlled and yields ONOO−, which exists in a protonated form (ONOOH) at physiological pH. Peroxynitrite undergoes rapid chemistry in water: isomerization to nitrate (NO3−) is possible, and reaction with CO2 forms nitrosoperoxocarboxylate (ONOOCO2−), which fragments to nitrogen dioxide (NO2) and carbonate radical (CO3•−). These secondary species can nitrate tyrosine residues to form 3-nitrotyrosine and oxidize lipids and DNA.

Peroxynitrite can modify proteins through nitration and oxidation, thereby altering enzyme activity, receptor function, and signaling pathways. Nitration of tyrosine residues is commonly used as a biomarker of nitrosative stress. It is implicated in inflammatory and neurodegenerative diseases, cardiovascular injury, sepsis, and ischemia–reperfusion damage. Its effects depend on concentration, localization, and the balance of antioxidant defenses.

Its transient nature makes direct measurement challenging; researchers often infer formation by detecting 3-nitrotyrosine, nitro-fatty acids, or by using targeted fluorescence probes and trapping agents. Understanding of peroxynitrite biology continues to evolve, as it sits at the intersection of redox signaling and oxidative injury.