Thermodynamic and kinetic considerations of Q-cycle mechanisms and the oxidant-induced reduction of cytochromesb

In coenzyme Q-cycles, it is proposed that one electron from the quinol reduces the Rieske iron sulfur center (E_m280 mV) and the remaining electron on the semiquinone reduces cytochromeb_T (E_m–60 mV). TheE_mfor the two-electron oxidation of the quinol is 60 mV and therefore the reduction of cytochromeb_T by quinol is not favorable. As the stability constant for the dismutation of the semiquinone decreases, the calculatedE_mfor the Q/QH couple is lowered to values below theE_mof cytochromeb_T. Contemporary coenzyme Q-cycles are based on the belief that the lower value for theE_mof the Q/QH couple compared to theE_mfor cytochromeb_T means that the semiquinone is a spontaneous reducing agent for theb-cytochrome. The analysis in the paper shows that this is not necessarily so and that neither binding sites nor ionization of the semiquinoneper se alters this situation. For a Q-cycle mechanism to function,ad hoc provisions must be made to drive the otherwise unfavorable reduction of cytochromeb_T by the semiquinone or for the simultaneous transfer of both electrons to cytochromeb_T and cytochromec₁ (or the iron sulfur protein). Q-cycle mechanisms with these additional provisions can explain the observation thus far accumulated. A linear path which is functionally altered by conformational changes may also explain the data.