Intra- and intermolecular oxidation of oxymyoglobin and oxyhemoglobin induced by hydroxyl and carbonate radicals

The mechanism of the reactions of myoglobin and hemoglobin with (OH)-O-center dot and CO3center dot- in the presence of oxygen was studied using pulse and gamma-radiolysis. Unlike NO2, which adds to the porphyrin iron, (OH)-O-center dot and CO3center dot- forin globin radicals. These secondary radicals oxidize the Fe-II center through both intra- and intermolecular processes. The intermolecular pathway was further demonstrated when BSA radicals derived from (OH)-O-center dot or CO3center dot- Oxidized oxyhemoglobin and oxymyoglobin to their respective ferric states. The oxidation yields obtained by pulse radiolysis were lower compared to gamma-radiolysis, where the contribution of radical-radical reactions is negligible. Full oxidation yields by (OH)-O-center dot-derived globin radicals could be achieved only at relatively high concentrations of the heme protein mainly via an intermolecular pathway. It is suggested that CO3center dot- reaction with the protein yields Tyr and/or Trp-derived phenoxyl radicals, which solely oxidize the porphyrin iron under gamma-radiolysis conditions. The (OH)-O-center dot particularly adds to aromatic residues, which can undergo elimination of H2O forming the phenoxyl radical, and/or react rapidly with O-2 yielding peroxyl radicals. The peroxyl radical can oxidize a neighboring porphyrin iron and/or give rise to superoxide, which neither oxidize nor reduce the porphyrin iron. The potential physiological implications of this chemistry are that hemoglobin and myoglobin, being present at relatively high concentrations, can detoxify highly oxidizing radicals yielding the respective ferric states, which are not toxic. (c) 2005 Elsevier Inc. All rights reserved.