REVIEW: Role of Cooperative H⁺/e^- Linkage (Redox Bohr Effect) at Heme a/Cu_A and Heme a₃/Cu_B in the Proton Pump of Cytochrome c Oxidase

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S. Papa

Institute of Bioenergetics and Biomembranes, National Council of Research (CNR); Department of Medical Biochemistry and Biology, University of Bari, 70124 Bari, Italy; fax: +39-080-5478109; E-mail: papabchm@cimedoc.uniba.it

Received September 24, 2004

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It is a pleasure to contribute to the special issue published in honor of Vladimir Skulachev, a distinguished scientist who greatly contributes to maintain a high standard of biochemical research in Russia. A more particular reason can be found in his work (Artzabanov, V. Y., Konstantinov, A. A., and Skulachev, V. P. (1978) FEBS Lett., 87, 180-185), where observations anticipating some ideas presented in my article were reported. Cytochrome c oxidase exhibits protonmotive, redox linked allosteric cooperativity. Experimental observations on soluble bovine cytochrome c oxidase are presented showing that oxido-reduction of heme a/Cu_A and heme a₃/Cu_B is linked to deprotonation/protonation of two clusters of protolytic groups, A₁ and A₂, respectively. This cooperative linkage (redox Bohr effect) results in the translocation of 1 H⁺/oxidase molecule upon oxido-reduction of heme a/Cu_A and heme a₃/Cu_B, respectively. Results on liposome-reconstituted oxidase show that upon oxidation of heme a/Cu_A and heme a₃/Cu_B protons from A₁ and A₂ are released in the outer aqueous phase. A₁ but not A₂ appears to take up protons from the inner aqueous space upon reduction of the respective redox center. A cooperative model is presented in which the A₁ and A₂ clusters, operating in close sequence, constitute together the gate of the proton pump in cytochrome c oxidase.

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KEY WORDS: cytochrome c oxidase, proton pump, cooperative coupling

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