[16] Nitrotyrosine as biomarker for reactive nitrogen species

This chapter discusses the modification of proteins by reactive nitrogen species (RNS) and of tyrosine residues. The mechanisms by which tyrosine is modified by nitrogen oxides (NO), and assay methods for 3-nitrotyrosine, a modified product of tyrosine specific for RNS is also described. The biological systems are commonly exposed to various oxides of nitrogen with the nitrogen atom present in various oxidation states, ranging from +1 to +5. Tyrosine modification by NO has received attention because one of the major products formed (3-nitrotyrosine) is a stable end product, and characteristic of nitrogen oxides. The analysis of modified tyrosine residues is also reviewed. RNS reacts with various amino acid residues in proteins, forming metabolites which may be specific for particular RNS. The analysis of specific products, such as 3-nitrotyrosine, is useful in determining formation of RNS in vivo. Reaction of NO2 . with tyrosine is demonstrated to result in formation of phenoxyl radicals that can either dimerize or combine with NO2 . to form 3-nitrotyrosine. The peroxynitrite (ONOO–) also oxidizes tyrosine to form both the dimer and 3-nitrotyrosine as the most important products.