The torsional mechanism of energy transduction and ATP synthesis as a breakthrough in our understanding of the mechanistic, kinetic and thermodynamic details

Abstract

Novel insights into mechanistic, kinetic and thermodynamic details of ATP synthesis by F1F0-ATP synthase in oxidative phosphorylation and photophosphorylation have been offered from the perspective of the torsional mechanism of energy transduction and ATP synthesis [Nath, S., Adv. Biochem. Eng. Biotechnol. 85 (2003) 125–180]; [Nath, S., Adv. Biochem. Eng. Biotechnol. 74 (2002) 65–98]. A fundamental energetic analysis of membrane phosphorylation has been performed that highlights the merits of the new paradigm. Biological implications for energy transduction have been discussed in detail. The action of uncouplers and inhibitors of oxidative phosphorylation has been explained by a fresh and completely different rationale. New experimental data that further supports the torsional mechanism has been presented, and the consistency of proposed mechanisms with the laws of thermodynamics has been assessed. A general kinetic analysis of oxygen exchange has been shown to reveal the absence of site-site cooperativity in F1-ATPase. Details of the nanomechanics of coupling between F1 and F0 in ATP hydrolysis-driven proton pumping have been postulated. The original thinking and power of the theoretical approaches embodied in the torsional mechanism have been shown to prove invaluable to unravel the functioning of other biological machines through a new Molecular Systems Biology. The generality and universality of the principles in the theory have been illustrated by taking specific examples of other molecular motors such as myosin and kinesin, revealing the deep underlying unity in diverse energy transduction processes in biology. Changes required in our scientific thinking and industrial technology and particularly in the education of the next generation of biological scientists have been identified as challenging issues that urgently need to be addressed in the near future.