Reaktionen von Peroxynitrit mit Biomolekülen

Peroxynitrite (PN) is formed in vivo in the reaction of nitric oxide (NO) with superoxide. PN is a powerful oxidant, which nitrates and hydroxylates phenols, but also leads to dimerization of such compounds. In this work some new products formed in the reaction of phenol with PN could be identified. Moreover the results of some experiments pointed towards a radical mechanism and the involvement of phenoxy radicals in this radical pathway. In a second part of this work several scavengers were tested for their efficiency to scavenge PN and inhibit harmful reactions with biotargets, such as the oxidation and inactivation of ADH, the nitration of phenol (as a model for tyrosine) and the nitration of BSA-bound tyrosines. For each of these reactions a number of antioxidants were employed and their IC50 values for the inhibition in these reactions were determined. In the last chapter the nitration by PN was investigated within two P450 enzymes: P450-BM3 and P450-CAM. These studies revealed that the nitration of some tyrosine residues is autocatalytic and therefore highly sensitive and selective. Moreover a ferryl (Compound II) spectrum could be observed for several P450 proteins, suggesting that it must be an obligatory and common intermediate in reactions of PN with P450 enzymes