How cytochrome c oxidase can pump four protons per oxygen molecule at high electrochemical gradient
2015 (English)In: Biochimica et Biophysica Acta - Bioenergetics, ISSN 0005-2728, E-ISSN 1879-2650, Vol. 1847, no 3, 364-376 p.Article in journal (Refereed) Published
Experiments have shown that the A-family cytochrome c oxidases pump four protons per oxygen molecule, also at a high electrochemical gradient. This has been considered a puzzle, since two of the reduction potentials involved, Cu(II) and Fe(III), were estimated from experiments to be too low to afford proton pumping at a high gradient The present quantum mechanical study (using hybrid density functional theory) suggests a solution to this puzzle. First, the calculations show that the charge compensated Cu(II) potential for Cu-B is actually much higher than estimated from experiment, of the same order as the reduction potentials for the tyrosyl radical and the ferryl group, which are also involved in the catalytic cycle. The reason for the discrepancy between theory and experiment is the very large uncertainty in the experimental observations used to estimate the equilibrium potentials, mainly caused by the lack of methods for direct determination of reduced Cu-B. Second, the calculations show that a high energy metastable state, labeled E-H, is involved during catalytic turnover. The E-H state mixes the low reduction potential of Fe(III) in heme a(3) with another, higher potential, here suggested to be that of the tyrosyl radical, resulting in enough exergonicity to allow proton pumping at a high gradient In contrast, the corresponding metastable oxidized state, O-H, is not significantly higher in energy than the resting state, O. Finally, to secure the involvement of the high energy E-H state it is suggested that only one proton is taken up via the K-channel during catalytic turnover.
Place, publisher, year, edition, pages
2015. Vol. 1847, no 3, 364-376 p.
Cytochrome c oxidase, Proton pumping, Density functional theory, Energy profile, Reduction potential
IdentifiersURN: urn:nbn:se:su:diva-115667DOI: 10.1016/j.bbabio.2014.12.005ISI: 000349589100006OAI: oai:DiVA.org:su-115667DiVA: diva2:800095