THE GENERATION OF PROTON ELECTROCHEMICAL POTENTIAL GRADIENT BY CYTOCHROME-C-OXIDASE

Cytochrome c oxidase, the terminal oxidase of mitochondria and some ba cteria, catalyzes the four electron reduction of oxygen, and generates a proton electrochemical potential gradient (Delta mu(H)). The recent ly determined structures of the bacterial and the bovine enzymes, toge ther with studies of site directed mutants of a bacterial cytochrome c oxidase and a closely related ubiquinol oxidase, have greatly advance d our understanding of the mechanism by which oxygen reduction is coup led to the generation of Delta mu(H). Two different mechanisms contrib ute to the generation of Delta mu(H): protons that are consumed by the reduction of oxygen, are taken exclusively from the mitochondrial mat rix ('consumed' protons), while other protons are translocated by the enzyme across the membrane ('pumped' protons). It is suggested that bo th proton consumption and proton pumping are driven by the electrostat ic charging of the enzyme reaction center by the reducing electrons. P roton consumption is suggested to result from the electrostatically dr iven ejection of hydroxyls into the matrix that is catalyzed by a tyro sine residue in the reaction center. Proton pumping is suggested to re sult from the electrostatically driven translocation of a glutamate re sidue near the reaction center, and is assisted by secondary accepters that release the translocated protons. (C) 1998 Elsevier Science B.V.