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Volume 271, Number 42, Issue of October 18, 1996 pp. 26018-26025
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Stimulation by Nitroxides of Catalase-like Activity of Hemeproteins
KINETICS AND MECHANISM

(Received for publication, June 6, 1996, and in revised form, July 2, 1996)

Murali C. Krishna , Amram Samuni ^¶ , Junsei Taira , Sara Goldstein ^¶ , James B. Mitchell and Angelo Russo

From the  Radiation Biology Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892 and the ^¶ Molecular Biology Department, Hebrew University Medical School, Jerusalem, 91120, Israel

The ability of stable nitroxide radicals to detoxify hypervalent heme proteins such as ferrylmyoglobin (MbFe^IV) produced in the reaction of metmyoglobin (MbFe^III) 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 MbFe^III was enhanced by stable nitroxides such as 4-OH-2,2,6,6-tetramethyl-piperidinoxyl (TPL) in a catalytic fashion. The reduction of MbFe^IV to MbFe^III was the rate-limiting step. Excess TPL over MbFe^III enhanced catalase-like activity more than 4-fold. During dismutation of H₂O₂, [TPL] and [MbFe^IV] 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 MbFe^IV 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 MbFe^III, thus facilitating H₂O₂ dismutation accompanied by O₂ evolution and providing protection against hypervalent heme proteins.

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