Field guide to Nath's research work on ATP synthesis and hydrolysis

Abstract

Adenosine triphosphate (ATP) is the universal biological energy source that participates in the most prevalent chemical reactions in all cell life through the vital processes of oxidative phosphorylation (OXPHOS) and photosynthesis. Its synthesis and utilisation is an area of basic research that has seen significant progress over the last three decades. A series of Nath's publications in the 1990s culminated in a detailed description of the molecular mechanism of ATP synthesis in the F_O and F₁ portions of F_OF₁-ATP synthase in which energy from transmembrane ion gradients in F_O are converted into chemical energy of ATP in F₁. Subsequent papers provided a thorough theoretical basis and exploration of the validity of the new theory—named by other authors as Nath's torsional mechanism of energy transduction and ATP synthesis and Nath's two-ion theory of energy coupling. Violation of several physical laws by previous theories have been dealt with in considerable detail. In particular he has reevaluated the extensive literature on ATP hydrolysis and provides a rigorously argued tri-site molecular mechanism involving the three filled β-catalytic sites during hydrolysis by F_O F₁/F₁-ATPase. Numerous applications have been proposed throughout his work that has resulted in four substantial publications dealing with re-interpretation of the Warburg Effect in cancer cells and a trilogy of papers dealing with biological thermodynamics of ATP synthesis applied to problems in comparative physiology, biochemistry and ecology. Finally strict mathematical methods have opened up new approaches to validate mechanistic events in ATP synthesis/hydrolysis. Here we provide a field guide for easy access to the different aspects of this body of work.