title: An alternating site sequence for oxidative phosphorylation suggested by measurement of substrate binding patterns and exchange reaction inhibitions.
abstract: Catalysis by beef heart submitochondrial particles of the medium Pi in equilibrium HOH, Pi in equilibrium ATP, and the ATP in equilibrium HOH exchanges is strongly inhibited while the ATPase and intermediate Pi in equilibrium HOH exchange are accelerated when medium ADP is removed by pyruvate kinase action. Arsenate readily blocks completely the Pi in equilibrium ATP and medium Pi in equilibrium HOH exchange reactions, but not the ATP in equilibrium HOH exchange reaction. The residual ATP in equilibrium HOH exchange in presence of arsenate is inhibited by 2,4-dinitrophenol. These results and other data are explained by an alternating site model for oxidative phosphorylation. In this model during net oxidative  phosphorylation ATP is formed at one site but is transitorily tightly bound and not released until ADP and Pi bind at a second site and the membrane ATPase complex is energized. Under conditions of net ATP hydrolysis, ATP binding at one site is accompanied by hydrolysis of the transitorily tightly bound ATP as a second site. Attractive features are only one site of input for conformational energization of the membrane ATPase, a single conformational transition that accounts for both the promotion of ADP and Pi binding in a competent mode and the release of tightly bound ATP, and a symmetry of catalytic sites. The Pi in equilibrium ATP exchange is not inhibited by increase in MgADP and MgATP at constant ratios, and the energy-linked ADP in equilibrium ATP exchange is not inhibited by increased concentrations of MgATP and Pi at a constant ratio. Such exchange patterns indicate a random binding and release of ADP and Pi.
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001149:Arsenates / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D004140:Dinitrophenols / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010710:Phosphates / Q000494:pharmacology
chemical_list: D001149:Arsenates; D002352:Carrier Proteins; D004140:Dinitrophenols; D010710:Phosphates; D000255:Adenosine Triphosphate; D008274:Magnesium