Abstract
The ability of stable nitroxide radicals to detoxify hypervalent heme proteins such as ferrylmyoglobin (MbFeIV) produced in the reaction of metmyoglobin (MbFeIII) and H2O2 was evaluated by monitoring O2 evolution, H2O2 depletion, and redox changes of the heme prosthetic group. The rate of H2O2 depletion and O2 evolution catalyzed by MbFeIII was enhanced by stable nitroxides such as 4-OH-2,2,6,6-tetramethyl-piperidinoxyl (TPL) in a catalytic fashion. The reduction of MbFeIV to MbFeIII was the rate-limiting step. Excess TPL over MbFeIII enhanced catalase-like activity more than 4-fold. During dismutation of H2O2, [TPL] and [MbFeIV] remained constant. NADH caused: (a) inhibition of H2O2 decay; (b) progressive reduction of TPL to its respective hydroxylamine TPL-H; and (c) arrest/inhibition of oxygen evolution or elicit consumption of O2. Following depletion of NADH the evolution of O2 resumed, and the initial concentration of TPL was restored. Kinetic analysis showed that two distinct forms of MbFeIV might be involved in the process. In summary, by shuttling between two oxidation states, namely nitroxide and oxoammonium cation, stable nitroxides enhance the catalase mimic activity of MbFeIII, thus facilitating H2O2 dismutation accompanied by O2 evolution and providing protection against hypervalent heme proteins.
Highlights
The ability of stable nitroxide radicals to detoxify hypervalent heme proteins such as ferrylmyoglobin (MbFeIV) produced in the reaction of metmyoglobin (MbFeIII) and H2O2 was evaluated by monitoring O2 evolution, H2O2 depletion, and redox changes of the heme prosthetic group
By shuttling between two oxidation states, namely nitroxide and oxoammonium cation, stable nitroxides enhance the catalase mimic activity of MbFeIII, facilitating H2O2 dismutation accompanied by O2 evolution and providing protection against hypervalent heme proteins
The results demonstrate the catalytic fashion by which nitroxides can facilitate the catalase-like activity of MbFeIV and substantiate the potential role of nitroxides in detoxification of H2O2 and reactive species such as ferryl
Summary
The ability of stable nitroxide radicals to detoxify hypervalent heme proteins such as ferrylmyoglobin (MbFeIV) produced in the reaction of metmyoglobin (MbFeIII) and H2O2 was evaluated by monitoring O2 evolution, H2O2 depletion, and redox changes of the heme prosthetic group. By shuttling between two oxidation states, namely nitroxide and oxoammonium cation, stable nitroxides enhance the catalase mimic activity of MbFeIII, facilitating H2O2 dismutation accompanied by O2 evolution and providing protection against hypervalent heme proteins. OxyMbFeII can undergo oxidation and yield MbFeIII and O2., which disproportionates to O2 and H2O2 [1] Such reactions were noted for hemoglobin [2]. No catalytic reactions are normally associated with myoglobin, modest peroxidase activity capable of oxidizing a variety of biological substrates has been identified [3,4,5]. The biologic significance of MbFeIV, stems from its ability to oxidize critical targets such as unsaturated fatty acids or mem-
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