International Journal of Molecular Sciences, Vol.9, No.9, 1784-1840, 2008
The new unified theory of ATP synthesis/hydrolysis and muscle contraction, its manifold fundamental consequences and mechanistic implications and its applications in health and disease
Complete details of the thermodynamics and molecular mechanisms of ATP synthesis/hydrolysis and muscle contraction are offered from the standpoint of the torsional mechanism of energy transduction and ATP synthesis and the rotation-uncoiling-tilt (RUT) energy storage mechanism of muscle contraction. The manifold fundamental consequences and mechanistic implications of the unified theory for oxidative phosphorylation and muscle contraction are explained. The consistency of current mechanisms of ATP synthesis and muscle contraction with experiment is assessed, and the novel insights of the unified theory are shown to take us beyond the binding change mechanism, the chemiosmotic theory and the lever arm model. It is shown from first principles how previous theories of ATP synthesis and muscle contraction violate both the first and second laws of thermodynamics, necessitating their revision. It is concluded that the new paradigm, ten years after making its first appearance, is now perfectly poised to replace the older theories. Finally, applications of the unified theory in cell life and cell death are outlined and prospects for future research are explored. While it is impossible to cover each and every specific aspect of the above, an attempt has been made here to address all the pertinent details and what is presented should be sufficient to convince the reader of the novelty, originality, breakthrough nature and power of the unified theory, its manifold fundamental consequences and mechanistic implications, and its applications in health and disease.
Keywords:bioenergetics;F1FO-ATP synthase;myosin and kinesin;mechanochemistry;energy transduction;torsional mechanism of energy transduction and ATP synthesis;rotation-uncoiling-tilt (RUT) energy storage mechanism of muscle contraction;quantized theory of biological molecular machines;apoptosis;molecular systems biology