Complete details of the thermodynamics and molecular mechanisms of ATP synthesis/hydrolysis …

• Abstract
• Introduction
• Unified Theory of the ATP Cycle in ATP Synthesis/Hydrolysis and Muscle Contraction
• Consistency of Current Mechanisms of ATP Synthesis and Muscle Contraction with KeyExperimental Data
• Fundamental Consequences of the Torsional Mechanism, the Rotation-Uncoiling-Tilt EnergyStorage Mechanism, and the Unified Theory for Molecular Mechanisms of ATPSynthesis/Hydrolysis and Muscle Contraction
• Beyond the Chemiosmotic Theory: Details of the Molecular Mechanism of EnergyTransduction in the Membrane-bound FO Portion of F1FO-ATP Synthase
• Applications of the Unified Theory to Other (Processive) Molecular Motors Crucial toCell Life
• Possible Applications of the Torsional Mechanism of ATP Synthesis and the Unified Theory inApoptosis, Cell Death and Disease
• Experimental Section
• Prospects for Future Research
• Conclusions
• References
• Figures

As research subjects the molecular mechanism of ATP synthesis and the molecular mechanism of muscle contraction have intrigued and captured the attention of several generations of scientists during the past ~75 and ~150 years, respectively, and a tremendous amount of experimental and theoretical work (that never ceases to defy this researcher’s imagination) has been done (for selected, longer, and more comprehensive reviews in this decade, see [1-5]). Yet, incredibly, this subject is still not fully understood, and several central fundamental issues remain unexplained, key aspects explored but failed to be resolved with finality, or not considered in adequate detail. Several stalwart researchers have dedicated their life to these problems [6-9] and continue to inspire younger generations of scientists. It may be possible for us to “stand on the shoulders of giants” and see beyond current paradigms, and by setting up novel research programs (along with some good fortune) to look at these difficult problems in a fresh and imaginative way that may lead to a better understanding, surmount the present obstacles facing us, and hopefully, even solve the enigmas and riddles we have been confronted with in these important fields of scientific endeavor.

One such research program on the mechanism and thermodynamics of molecular machines funded during the past ~15 years has led to new thinking and analysis through the conception and detailed formulation of the torsional mechanism of energy transduction and ATP synthesis and the rotation uncoiling- tilt (RUT) energy storage mechanism of muscle contraction [1, 2, 10-29]. In this paper, further subtle but crucial, fundamental details of the molecular mechanisms of ATP synthesis and muscle contraction and their consequences that had remained inaccessible are revealed from the standpoint of the torsional and RUT mechanisms and unification of the thermodynamic ATP cycle. Some current theories are shown to be in disagreement with important biochemical and biophysical (including single molecule) data. Moreover, in a very simple way, it is shown why and how previous theories violate both the first and second laws of thermodynamics and hence require revision. Such difficulties are not present in the new paradigm, which is now perfectly poised to replace the older theories. Finally, emphasis is laid on the biological applications of the unified theory in cell life and death, and how several scientific doors can be opened leading to new vistas and opportunities for future research.