Nitrotyrosine, dityrosine, and nitrotryptophan formation from metmyoglobin, hydrogen peroxide, and nitrite

The biological relevance of tyrosine nitration is a subject of much interest, because extensive evidence supports formation of 3-nitrotyrosine in vivo under a variety of different pathological conditions. Several reagents are likely to be responsible for nitration in vivo, among others peroxynitrite and nitrite in the presence of H2O2/peroxidases. In this work we show that also metmyoglobin and methemoglobin can nitrate free tyrosine in the presence of nitrite and H2O2. The results of these studies are simulated rather well by using a scheme that comprehends all the possible reactions that can take place in the system. Thus, a good understanding of the factors that determine the yields is achieved. Finally, we demonstrate that the system metMb/H2O2/NO2- can also lead to the nitration of tryptophan and produces, in particular, 6-, 4-, and 5-nitrotryptophan. (C) 2004 Elsevier Inc. All rights reserved.