Oxidative phosphorylation: kinetic and thermodynamic correlation between electron flow, proton translocation, oxygen consumption and ATP synthesis under close to in vivo concentrations of oxygen.
For the fist time the mitochondrial process of oxidative phosphorylation has been studied by determining the extent and initial rates of electron flow, H+ translocation, O2 uptake and ATP synthesis under close to in vivo concentrations of oxygen. The following novel results were obtained. 1) The real rates of O2 uptake and ATP synthesis are orders of magnitude higher than those observed under state-3 metabolic conditions. 2) The phosphorylative process of ATP synthesis is neither kinetically nor thermodynamically related to the respiratory process of H+ ejection. 3) The ATP/O stoichiometry is not constant but varies depending on all, the redox potential (DeltaE(h)), the degree of reduction of the membrane and the relative concentrations of O2, ADP, and protein. 4) The free energy of electron flow is not only used for the enzymatic binding and release of substrates and products but fundamentally for the actual synthesis of ATP from ADP and Pi. 5) The concentration of ADP that produces half-maximal responses of ATP synthesis (EC50) is not constant but varies depending on both DeltaE(h) and O2 concentration. 6) The process of ATP synthesis exhibits strong positive catalytic cooperativity with a Hill coefficient, n, of approximately 3.0. It is concluded that the most important factor in determining the extent and rates of ATP synthesis is not the level of ADP or the proton gradient but the concentration of O2 and the state of reduction and/or protonation of the membrane.
Johns Hopkins University School of Medicine, Department of Biological Chemistry, Baltimore, Maryland 21205, USA.
Baltazar D
BD
Reynafarje
Jorge
J
Ferreira
D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004579:Electron Transport; D006801:Humans; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D010766:Phosphorylation; D011522:Protons; D013816:Thermodynamics
D011522:Protons; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D010100:Oxygen