HEMOGLOBİN VE NİTRİT BAĞIMLI TİROZİN NİTRASYONU

Abstract

Nitric oxide (NO) reacts with oxyhemoglobin or oxymyoglobin resulting in the generation of nitrate and metHb or metMb. Unlike the case of nitrate, nitrite is not an innocuous end product of NO oxidation. Hemoproteins including several peroxidases are shown to cause nitrite oxidation in the presence of H2O2. Reactive nitrogen oxides generated in hemoprotein-catalyzed nitrite oxidation are held responsible for bactericidal and cytotoxic actions of nitrite. In this study with Griess method the oxidation of nitrite to nitrate in the presence of H2O2 by hemoglobin were searched. No nitrite oxidation was observed either in the absence of H2O2 or hemoglobin, showing that the reactive species causing nitrite oxidation is a oxoferryl complex (compound I) formed from the reaction of H2O2 with hemoglobin. In this study, similar to peroxidase enzymes, we found that hemoglobin causes the nitration of tyrosine. Hemoglobin-catalyzed tyrosine nitration was pH-dependent with the optimum pH of 6,0. Hemoglobin and H2O2 were essential components for tyrosine nitration. We have not observed any tyrosine nitration without hemoglobin even at the lowest pH studied. However during hemoglobin-catalyzed nitrite oxidation in the presence of H2O2, nitrating species are produced. We conclude that, by the series of reactions between hemoglobin, H2O2 and nitrite, nitrogen dioxide radical (NO2 - ) and/or peroxynitrite like reactive species are produced, and these species are responsible for tyrosine nitration.