Signaling Actions of Electrophiles: Anti-inflammatory Therapeutic Candidates

Multiple mechanisms can lead to the nitration of lipids. A. Biologically relevant NO₂-FA products resulting from reaction of PUFA with NO_X and reactive oxygen species. B. Reactive intermediates from autoxidation of ^•NO and acidification of nitrite. Under aerobic conditions ^•NO can react rapidly with O₂ to form ^•NO₂. When the O₂ concentration is significantly lower than atmospheric conditions, ^•NO₂ and ^•NO can be in equilibrium with N₂O₃. In aqueous milieu, N₂O₃ can be in equilibrium with HNO₂. Finally, HNO₂ is in equilibrium with is conjugate base NO₂⁻ (pKa=3.35). As all of these reactions are reversible, their order and equilibria depend on the source and site of production of NO_X, the concentrations of various intermediates, and their reaction with other biomolecules.