Cytochrome c oxidase: catalytic cycle and mechanisms of proton pumping--a discussion

Biochemistry. 1999 Nov 16;38(46):15129-40. doi: 10.1021/bi9910934.

Abstract

Cytochrome c oxidase catalyzes the reduction of molecular oxygen to water, a process in which four electrons, four protons, and one molecule of oxygen are consumed. The reaction is coupled to the pumping of four additional protons across the membrane. According to the currently accepted concept, the pumping of all four protons occurs after the binding of oxygen to the reduced enzyme and is exclusively coupled to the last two electron transfer steps. A careful analysis of the existing data shows that there is no experimental evidence for this paradigm. It is more likely that only three protons are pumped during the second half of the catalytic cycle of cytochrome c oxidase after the reaction with oxygen. In this article a variant of a recent mechanistic model of proton pumping by electrostatic repulsion is discussed. It is based on the electroneutrality principle in a way that in the catalytic cycle each electron transfer to the membrane-embedded electron acceptors is charge-compensated by uptake of one proton. The mechanism takes into account the findings with mutant cytochrome c oxidases and explains the results of many recent experiments, including the effects of hydrogen peroxide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Catalysis
  • Electron Transport / genetics
  • Electron Transport Complex IV / chemistry*
  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism
  • Models, Chemical
  • Mutagenesis, Site-Directed
  • Proton Pumps / chemistry*
  • Proton Pumps / genetics
  • Proton Pumps / metabolism
  • Static Electricity

Substances

  • Proton Pumps
  • Electron Transport Complex IV