Routes of cytochrome a3 reduction. The neoclassical model revisited

A model for cytochrome oxidase is presented in which cytochrome a, cytochrome a3, and CuB are mutally interacting centers. Cytochrome a3, at equilibrium, is always reduced after CuB. The redox potential of cytochrome a declines progressively as the a3 CuB center is reduced. Dithionite reduction involves up to five steps: (i) reduction of cytochrome a and CuA; (ii) reduction of CuB; (iii) dissociation of ligands (exogenous and endogenous) from cytochrome a3; (iv) spin state changes (high to low) in cyt. a3 and (v) reduction of cytochrome a3. Any of (ii), (iii), and (iv) may be implicated as part of the slow step in this process, which is seen in the resting enzyme.