A protet-based, protonic charge transfer model of energy coupling in oxidative and photosynthetic phosphorylation

Kell, Douglas B.

doi:10.1016/bs.ampbs.2021.01.001

Cited by 14 publications

(5 citation statements)

References 1,161 publications

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“…According to the literature, the transmembrane proton and electrochemical potential Δp from electron transport are mechanically transmitted to the hexamer of the αβ-subunits. The step-wise rotation of the F1/F0 complex is the result when ADP reacts with Pi to form ATP tightly bound in the first instance and a second configuration which allows ATP to be released [35,38]. Apart from this, another crucial feature lacking a molecular description is how rotation driven by Δp is generated, and how rotation transmits energy into the catalytic sites of the enzyme to produce the stepping action during rotation [39].…”

Section: The Role Of H₂o-h₂o Hydrogen Bondingmentioning

confidence: 99%

A 3-Dimensional Hypothesis of Oxidative Phosphorylation

Knight¹

2023

Vasc Cell

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In general, hitherto, all scholarly illustrations of oxidative phosphorylation are schematically presented in two dimensions as in Fig. 1, where the electron current is shown resulting in the transmembrane proton gradient driving the formation of ATP via the F1F0-ATPase [1]. In this hypothesis, the electrical gradient that results from electron transport induces a conformational change of the F1F0-ATPase coupled with a change of hydrogen bonding of a strategic shell of H₂O molecules, favouring the thermodynamics of the reaction ADP with inorganic phosphate (Pi) to produce ATP. This hypothesis presents the whole coupling process of the mitochondrial inner membrane in three dimensions, essential for this particulate biochemistry [1,2].

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Section: The Role Of H₂o-h₂o Hydrogen Bondingmentioning

confidence: 99%

A 3-Dimensional Hypothesis of Oxidative Phosphorylation

Knight¹

2023

Vasc Cell

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“…Thermodynamic [23][24][25][26][27], electrostatic [28][29][30] and molecular systems biology/engineering [31][32][33] approaches have also been developed to understand the function of these complex nanosystems. The developments in ATP and cell life [33][34][35][36][37][38] and cell death [39][40][41][42][43][44][45][46][47] have been reviewed previously.…”

Section: Introductionmentioning

confidence: 99%

Phosphorus Chemistry at the Roots of Bioenergetics: Ligand Permutation as the Molecular Basis of the Mechanism of ATP Synthesis/Hydrolysis by FOF1-ATP Synthase

Nath

2023

Molecules

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The integration of phosphorus chemistry with the mechanism of ATP synthesis/hydrolysis requires dynamical information during ATP turnover and catalysis. Oxygen exchange reactions occurring at β-catalytic sites of the FOF1-ATP synthase/F1-ATPase imprint a unique record of molecular events during the catalytic cycle of ATP synthesis/hydrolysis. They have been shown to provide valuable time-resolved information on enzyme catalysis during ATP synthesis and ATP hydrolysis. The present work conducts new experiments on oxygen exchange catalyzed by submitochondrial particles designed to (i) measure the relative rates of Pi–ATP, Pi–HOH, and ATP–HOH isotope exchanges; (ii) probe the effect of ADP removal on the extent of inhibition of the exchanges, and (iii) test their uncoupler sensitivity/resistance. The objectives have been realized based on new experiments on submitochondrial particles, which show that both the Pi–HOH and ATP–HOH exchanges occur at a considerably higher rate relative to the Pi–ATP exchange, an observation that cannot be explained by previous mechanisms. A unifying explanation of the kinetic data that rationalizes these observations is given. The experimental results in (ii) show that ADP removal does not inhibit the intermediate Pi–HOH exchange when ATP and submitochondrial particles are incubated, and that the nucleotide requirement of the intermediate Pi–HOH exchange is adequately met by ATP, but not by ADP. These results contradicts the central postulate in Boyer’s binding change mechanism of reversible catalysis at a F1 catalytic site with Keq~1 that predicts an absolute requirement of ADP for the occurrence of the Pi–HOH exchange. The prominent intermediate Pi–HOH exchange occurring under hydrolytic conditions is shown to be best explained by Nath’s torsional mechanism of energy transduction and ATP synthesis/hydrolysis, which postulates an essentially irreversible cleavage of ATP by mitochondria/particles, independent from a reversible formation of ATP from ADP and Pi. The explanation within the torsional mechanism is also shown to rationalize the relative insensitivity of the intermediate Pi–HOH exchange to uncouplers observed in the experiments in (iii) compared to the Pi–ATP and ATP–HOH exchanges. This is shown to lead to new concepts and perspectives based on ligand displacement/substitution and ligand permutation for the elucidation of the oxygen exchange reactions within the framework of fundamental phosphorus chemistry. Fast mechanisms that realize the rotation/twist, tilt, permutation and switch of ligands, as well as inversion at the γ-phosphorus synchronously and simultaneously and in a concerted manner, have been proposed, and their stereochemical consequences have been analyzed. These considerations take us beyond the binding change mechanism of ATP synthesis/hydrolysis in bioenergetics.

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“…In addition, electrostatic [29,30] and molecular systems biology/engineering [31][32][33] approaches were developed to understand function. Several reviews on the rapid developments in ATP and cell life [33][34][35][36][37][38] and cell death [39][40][41][42][43][44][45][46][47] were written. A crucial central question was the following: How could time-resolved information [48][49][50][51][52] on elementary events occurring in single catalytic sites of enzymes, such as in the β-subunits of the F 1 -ATPase, be gathered and interpreted?…”

Section: Introductionmentioning

confidence: 99%

Elucidating Events within the Black Box of Enzyme Catalysis in Energy Metabolism: Insights into the Molecular Mechanism of ATP Hydrolysis by F1-ATPase

Nath

2023

Biomolecules

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Oxygen exchange reactions occurring at β-catalytic sites of the FOF1-ATP synthase/F1-ATPase imprint a unique record of molecular events during the catalytic cycle of ATP synthesis/hydrolysis. This work presents a new theory of oxygen exchange and tests it on oxygen exchange data recorded on ATP hydrolysis by mitochondrial F1-ATPase (MF1). The apparent rate constant of oxygen exchange governing the intermediate Pi–HOH exchange accompanying ATP hydrolysis is determined by kinetic analysis over a ~50,000-fold range of substrate ATP concentration (0.1–5000 μM) and a corresponding ~200-fold range of reaction velocity (3.5–650 [moles of Pi/{moles of F1-ATPase}−1 s−1]). Isotopomer distributions of [18O]Pi species containing 0, 1, 2, and 3 labeled oxygen atoms predicted by the theory have been quantified and shown to be in perfect agreement with the experimental distributions over the entire range of medium ATP concentrations without employing adjustable parameters. A novel molecular mechanism of steady-state multisite ATP hydrolysis by the F1-ATPase has been proposed. Our results show that steady-state ATP hydrolysis by F1-ATPase occurs with all three sites occupied by Mg-nucleotide. The various implications arising from models of energy coupling in ATP synthesis/hydrolysis by the ATP synthase/F1-ATPase have been discussed. Current models of ATP hydrolysis by F1-ATPase, including those postulated from single-molecule data, are shown to be effectively bisite models that contradict the data. The trisite catalysis formulated by Nath’s torsional mechanism of energy transduction and ATP synthesis/hydrolysis since its first appearance 25 years ago is shown to be in better accord with the experimental record. The total biochemical information on ATP hydrolysis is integrated into a consistent model by the torsional mechanism of ATP synthesis/hydrolysis and shown to elucidate the elementary chemical and mechanical events within the black box of enzyme catalysis in energy metabolism by F1-ATPase.

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A protet-based, protonic charge transfer model of energy coupling in oxidative and photosynthetic phosphorylation

Cited by 14 publications

References 1,161 publications

A 3-Dimensional Hypothesis of Oxidative Phosphorylation

A 3-Dimensional Hypothesis of Oxidative Phosphorylation

Phosphorus Chemistry at the Roots of Bioenergetics: Ligand Permutation as the Molecular Basis of the Mechanism of ATP Synthesis/Hydrolysis by FOF1-ATP Synthase

Elucidating Events within the Black Box of Enzyme Catalysis in Energy Metabolism: Insights into the Molecular Mechanism of ATP Hydrolysis by F1-ATPase

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