Concerted involvement of cooperative proton-electron linkage and water production in the proton pump of cytochrome c oxidase

In cytochrome c oxidase, oxido-reductions of heme a/Cu-A and heme a(3)/CUB are cooperatively linked to proton transfer at acidibase groups in the enzyme. H+/e(-) cooperative linkage at Fe-a3/Cu-B is envisaged to be involved in proton pump mechanisms confined to the binuclear center. Models have also been proposed which involve a role in proton pumping of cooperative H+/e- linkage at heme a (and Cu-A). Observations will be presented on: (i) proton consumption in the reduction of molecular oxygen to H2O in soluble bovine heart cytochrome c oxidase; (ii) proton release/uptake associated with anaerobic oxidation/reduction of heme a/Cu-A and heme a(3)/Cu-B in the soluble oxidase; (iii) H+ release in the external phase (i.e. H+ pumping) associated with the oxidative (R -> O transition), reductive (O -> R transition) and a full catalytic cycle (R -> O -> R transition) of membrane-reconstituted cytochrome c oxidase. A model is presented in which cooperative H+/e(-) linkage at heme a/Cu-A and heme a(3)/Cu-B with acid/base clusters, C-1 and C-2 respectively, and protonmotive steps of the reduction of O-2 to water are involved in proton pumping. (c) 2006 Elsevier B.V. All rights reserved.