The pathobiochemistry of nitrogen dioxide

Nitrogen dioxide (.NO2) is an oxidizing free radical which can initiate a variety of destructive pathways in living systems, and several diseases are suspected to be connected with both exogenously and endogenously formed .NO2. Peroxynitrite (ONOO-/ONOOH) is believed to be an important endogenous source of .NO2 radicals, but other sources, among them enzymatically ones, have been identified recently. It also became clear during the last few years that in vivo formation of 3-nitrotyrosine strictly depends on the availability of .NO2 radicals. Since nitrogen dioxide is a very toxic compound an arsenal of antioxidants (e.g. vitamin C, glutathione, vitamin E, and P-carotene) must eliminate this harmful radical in vivo. Here the recently identified superoxide (O-2(.-))-dependent formation of peroxynitrate (O2NOO-) and the central role of vitamin C are of special importance.