title: The generation of proton electrochemical potential gradient by cytochrome c oxidase.
abstract: Cytochrome c oxidase, the terminal oxidase of mitochondria and some bacteria, catalyzes the four electron reduction of oxygen, and generates a proton electrochemical potential gradient (Delta microH). The recently determined structures of the bacterial and the bovine enzymes, together with studies of site directed mutants of a bacterial cytochrome c oxidase and a closely related ubiquinol oxidase, have greatly advanced our understanding of the mechanism by which oxygen reduction is coupled to the generation of Delta microH. Two different mechanisms contribute to the generation of Delta microH: protons that are consumed by the reduction of oxygen, are taken exclusively from the mitochondrial matrix ('consumed' protons), while other protons are translocated by the enzyme across the membrane ('pumped' protons). It is suggested that both proton consumption and proton pumping are driven by the electrostatic charging of the enzyme reaction center by the reducing electrons. Proton consumption is suggested to result from the electrostatically driven ejection of hydroxyls into the matrix that is catalyzed by a tyrosine residue in the reaction center. Proton pumping is suggested to result from the electrostatically driven translocation of a glutamate residue near the reaction center, and is assisted by secondary acceptors that release the translocated protons.
authors.affiliation: Allegheny University of the Health Sciences, MCP/Hahnemann School of Medicine, Pathology Department, Philadelphia, PA 19102, USA. rottenbergh@auhs.edu
authors.forename: H
authors.initials: H
authors.lastname: Rottenberg
mesh_terms: D000818:Animals; D001419:Bacteria / Q000201:enzymology*; D001665:Binding Sites; D002417:Cattle; D004563:Electrochemistry; D003576:Electron Transport Complex IV / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008928:Mitochondria / Q000201:enzymology*; D016297:Mutagenesis, Site-Directed; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity; D014443:Tyrosine
chemical_list: D011994:Recombinant Proteins; D014443:Tyrosine; D003576:Electron Transport Complex IV