Reactive nitrogen species generated by heme proteins: Mechanism of formation and targets

Nitration of tyrosine residues in proteins represents a pathological event that is associated with several human and animal diseases. Besides the classical pathways of formation of reactive nitrogen species (RNS) by NO oxidation, several studies show that heme peroxidases also play an important role in RNS generation. The mechanism of generation of these species has been studied in detail focusing on the nitration of several tyrosine and tryptophan derivatives. Also the O2-storage and O2-carrier heme proteins, myoglobin and hemoglobin, can induce RNS formation and promote self-nitration and oxidation. These reactions bear biological relevance and, therefore, the identification of the sites of endogenous modification of these proteins has been carried out by proteomic analysis.