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
Sunil Nath 1,2
1
Department of Biochemical Engineering and Biotechnology, Indian
Institute of Technology, Delhi, Hauz Khas, New Delhi 110016, India
2
Present address: Visiting Professor, Department of Structural Biology,
Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124
Braunschweig, Germany
Int. J. Mol. Sci. 2008, Volume 9(9), Page 1784-1840; DOI: 10.3390/ijms9091784. An Open Access Article
Abstract: 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