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
Abstract
:1. Introduction
2. Unified Theory of the ATP Cycle in ATP Synthesis/Hydrolysis and Muscle Contraction
2.1. Specific Details of Energy Distribution among the Elementary Steps of Binding, Bond Cleavage, and Product Release in the ATP Synthesis/Hydrolysis Catalytic Cycle
2.2. Contradictory Assumptions and Gross Inconsistencies among Previous Models as Seen from the Viewpoint of the Unified Theory
2.3. Further Fundamental Differences between the Torsional Mechanism of ATP Synthesis and the Binding Change Mechanism
2.4. Further Development of the Torsional Mechanism of ATP Synthesis/Hydrolysis, the Rotation-Uncoiling-Tilt (RUT) Energy Storage Mechanism of Muscle Contraction and the Unified Theory
2.4.1. Complete Details of Quantized Release and Utilization of Energy in the Synthesis Mode and its Mechanistic Implications
2.4.2. Quantized Release and Utilization of Energy in the Hydrolysis Mode and Its Mechanistic Implications for Muscle Contraction
2.4.3. Complete Details of Quantized Release and Utilization of Energy in the Hydrolysis Mode and its Mechanistic Implications for F1-ATPase
2.5. Removal of the Various Inconsistencies in Previous Models by the Unified Theory
2.5.1. Models of Muscle Contraction and Motility
2.5.2. Models in Bioenergetics
2.6. Kinetic Analysis of ATP Hydrolysis by F1-ATPase
3. Consistency of Current Mechanisms of ATP Synthesis and Muscle Contraction with Key Experimental Data
3.1. Bioenergetics
3.1.1. Nucleotide Binding Affinity (Kd) Measurements at the Catalytic Sites of F1-ATPase
3.1.2. Structure of Mitochondrial F1-ATPase with Nucleotide Bound to All Three Catalytic Sites
3.2. Muscle Contraction
3.2.1. Contraction Characteristics and ATPase Activity of Muscle Fibers in the Presence of Antibody to Myosin S-2
3.2.2. Single Molecule Imaging
4. Fundamental Consequences of the Torsional Mechanism, the Rotation-Uncoiling-Tilt Energy Storage Mechanism, and the Unified Theory for Molecular Mechanisms of ATP Synthesis/Hydrolysis and Muscle Contraction
4.1. Violations of the First Law of Thermodynamics by Previous Mechanisms of ATP Synthesis and Muscle Contraction
4.2. Violations of the Second Law of Thermodynamics by Previous Mechanisms of ATP Synthesis and Muscle Contraction
4.3. Mechanistic H+/O, H+/ATP and P/O Ratios, Efficiency of Oxidative Phosphorylation, and the Overall Energy Balance of Cellular Bioenergetics
5. Beyond the Chemiosmotic Theory: Details of the Molecular Mechanism of Energy Transduction in the Membrane-bound FO Portion of F1FO-ATP Synthase
5.1. Several Lines of Biochemical Evidence that Cannot be Accounted for by the Chemiosmotic Theory but Are Logically Explained by the Torsional Mechanism of Energy Transduction and ATP Synthesis
5.2. Establishment of the Type of Inhibition Found with Potent, Specific Anion Channel Blockers Such as DIDS and its Logical Explanation
5.3. Explanation of Rate Enhancement of ATP Synthesis at Very High Inhibitor Concentrations
5.4. Precise Explanation of Uncoupling Action by Weak Acid Anion Uncouplers of Oxidative Phosphorylation
5.5. The Way Forward
6. Applications of the Unified Theory to Other (Processive) Molecular Motors Crucial to Cell Life
7. Possible Applications of the Torsional Mechanism of ATP Synthesis and the Unified Theory in Apoptosis, Cell Death and Disease
8. Experimental Section
8.1. Isolation of Thylakoid Membranes
8.2. Estimation of Chlorophyll Content
8.3. Measurement of ATP Synthesis
8.4. Estimation and Calculation of Rates of ATP Synthesis
9. Prospects for Future Research
10. Conclusions
Acknowledgments
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Nath, S. 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. Int. J. Mol. Sci. 2008, 9, 1784-1840. https://doi.org/10.3390/ijms9091784
Nath S. 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. International Journal of Molecular Sciences. 2008; 9(9):1784-1840. https://doi.org/10.3390/ijms9091784
Chicago/Turabian StyleNath, Sunil. 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" International Journal of Molecular Sciences 9, no. 9: 1784-1840. https://doi.org/10.3390/ijms9091784