Proteins and Carbon Dioxide Struggle Against Peroxynitrite

Nitrosative stress plays a key role in the etiology of several human diseases, such as atherosclerosis, inflammation, cancer, and neurological diseases. Peroxynitrite is one of the most potent biological nitrosative agents, being produced at extremely rapid rates when nitric oxide (^●NO) and superoxide (^●O₂ ^-) are combined. Peroxynitrite undergoes self-degradation at a slow rate, yielding ~70% nitrate (NO₃ ^-) and H⁺, and ~30% nitrite (NO₂ ^-) and dioxygen (O₂). Peroxynitrite degradation can be speeded up by the interaction with either (i) carbon dioxide (CO₂), through the transient formation of 1-carboxylato-2-nitrosodioxidane adduct (ONOOC(O)O^-), which eventually decays to CO₂ and NO₃ ^- via the intermediate strong oxidants trioxocarbonate (CO₃ ^●-) and (nitrogen dioxide) ^●NO₂ ^-, and/or (ii) proteins, such as thiol peroxidases and heme-proteins by different mechanisms. Under physiological conditions, peroxynitrite detoxification, which brings about different effects on the cellular metabolism, depends on the relative concentration of CO₂ and proteins. In this review, we analyze the intrinsic parameters of processes involved in peroxynitrite scavenging, which are crucial in poorly oxygenated tissues (such as the retina), exploring conditions that alternatively favor one process or the other.