Molecular mechanistic insights into coupling of ion transport to ATP synthesis

A wealth of molecular mechanistic insights has been provided into the coupling of ion transport to ATP synthesis based on a two-ion theory of biological energy coupling. A kinetic scheme that considers the mode of functioning of a single F1FO-ATP synthase molecule with H+-A(-) cotransport and unidirectional rotation of the c-rotor in the membrane-bound F-O-portion of the enzyme has been developed. Mathematical analysis leads to a detailed enzyme kinetic model applicable to a population of molecules which is compared with experimental data on the pH dependence of ATP synthesis. The model agrees well with the experimental data, and a single equation with a single set of standard enzymological kinetic parameters has been shown to explain the experimental data over the entire range of conditions for the chloroplast ATP synthase. The analysis gives novel insights into kinetic and mechanistic characteristics of ATP synthesis in F-O. These include an order imposed on ion binding and unbinding events in F-O, the essential role of the anion in direct activation of the ATP synthase (in addition to its role as a permeant ion), and the integration in a novel way of the functions of cooperativity and cotransport of dicarboxylic acid anions and protons during physiological ATP synthesis. Further, Wyman's pioneering classical work on the thermodynamics of linked functions has been shown to offer a new approach to distinguish between various models of energy coupling in ATP synthesis. All these results have been found to be inconsistent with Mitchell's chemiosmotic theory and are shown to be in agreement with Nath's torsional mechanism of energy transduction and ATP synthesis.