The torsional mechanism of energy transduction and ATP synthesis as a breakthrough in our understanding of the mechanistic, kinetic and thermodynamic details

2004 ◽  
Vol 422 (1-2) ◽  
pp. 5-17 ◽  
Author(s):  
Sunil Nath
Keyword(s):  
Atp Synthesis ◽  
Energy Transduction ◽  
Torsional Mechanism

scholarly journals Entropy Production and Its Application to the Coupled Nonequilibrium Processes of ATP Synthesis

Entropy ◽  
2019 ◽  
Vol 21 (8) ◽  
pp. 746 ◽  
Author(s):  
Sunil Nath
Keyword(s):  
Experimental Data ◽  
Entropy Production ◽  
Physiological State ◽  
Atp Synthesis ◽  
Energy Coupling ◽  
Energy Transduction ◽  
Theoretical Research ◽  
Thermodynamic Efficiency ◽  
Chemiosmotic Theory ◽  
Torsional Mechanism

Starting from the universal concept of entropy production, a large number of new results are obtained and a wealth of novel thermodynamic, kinetic, and molecular mechanistic insights are provided into the coupling of oxidation and ATP synthesis in the vital process of oxidative phosphorylation (OX PHOS). The total dissipation, Φ , in OX PHOS with succinate as respiratory substrate is quantified from measurements, and the partitioning of Φ into the elementary components of ATP synthesis, leak, slip, and other losses is evaluated for the first time. The thermodynamic efficiency, η , of the coupled process is calculated from the data on Φ and shown to agree well with linear nonequilibrium thermodynamic calculations. Equations for the P/O ratio based on total oxygen consumed and extra oxygen consumed are derived from first principles and the source of basal (state 4) mitochondrial respiration is postulated from molecular mechanistic considerations based on Nath’s two-ion theory of energy coupling within the torsional mechanism of energy transduction and ATP synthesis. The degree of coupling, q , between oxidation and ATP synthesis is determined from the experimental data and the irreversible thermodynamics analysis. The optimality of biological free energy converters is explored in considerable detail based on (i) the standard biothermodynamic approach, and (ii) a new biothermokinetic approach developed in this work, and an effective solution that is shown to arise from consideration of the molecular aspects in Nath’s theory is formulated. New experimental data in state 4 with uncouplers and redox inhibitors of OX PHOS and on respiratory control in the physiological state 3 with ADP and uncouplers are presented. These experimental observations are shown to be incompatible with Mitchell’s chemiosmotic theory. A novel scheme of coupling based on Nath’s two-ion theory of energy coupling within the torsional mechanism is proposed and shown to explain the data and also pass the test of consistency with the thermodynamics, taking us beyond the chemiosmotic theory. It is concluded that, twenty years since its first proposal, Nath’s torsional mechanism of energy transduction and ATP synthesis is now well poised to catalyze the progress of experimental and theoretical research in this interdisciplinary field.

scholarly journals Effect of 3,5-di-iodo-L-thyronine on the mitochondrial energy-transduction apparatus

1998 ◽  
Vol 330 (1) ◽  
pp. 521-526 ◽  
Author(s):  
Assonta LOMBARDI ◽  
Antonia LANNI ◽  
Maria MORENO ◽  
D. Martin BRAND ◽  
Fernando GOGLIA
Keyword(s):  
Cytochrome C ◽  
Mitochondrial Respiration ◽  
Atp Synthesis ◽  
Substrate Oxidation ◽  
Energy Transduction ◽  
Energy Utilization ◽  
Proton Leak ◽  
Elasticity Analysis ◽  
Top Down ◽  
Respiratory State

We examined the effect of a single injection of 3,5-di-iodo-l-thyronine (3,5-T2) (150 μg/100 g body weight) on the rat liver mitochondrial energy-transduction apparatus. We applied ‘top-down’ elasticity analysis, which allows identification of the site of action of an effector within a metabolic pathway. This kinetic approach considers oxidative phosphorylation as two blocks of reactions: those generating the mitochondrial inner-membrane potential (Δψ; ‘substrate oxidation’) and those ‘consuming’ it (‘proton leak’ and ‘phosphorylating system’). The results show that 1 h after the injection of 3,5-T2, state 4 (respiratory state in which there is no ATP synthesis and the exogenous ADP added has been exhausted) and state 3 (respiratory state in which ATP synthesis is at maximal rate) of mitochondrial respiration were significantly increased (by approx. 30%). ‘Top-down’ elasticity analysis revealed that these increases were due to the stimulation of reactions involved in substrate oxidation; neither ‘proton leak’ nor the ‘phosphorylating system’ was influenced by 3,5-T2. Using the same approach we divided the respiratory chain into two blocks of reactions: cytochrome c reducers and cytochrome c oxidizers. We found that both cytochrome c reducers and cytochrome c oxidizers are targets for 3,5-T2. The rapidity with which 3,5-T2 acts in stimulating the mitochondrial respiration rate suggests to us that di-iodo-L-thyronine may play an important role in the physiological conditions in which rapid energy utilization is required, such as cold exposure or overfeeding.

Proton semiconductors and energy transduction in biological systems

1978 ◽  
Vol 235 (3) ◽  
pp. R99-R114 ◽  
Author(s):  
H. J. Morowitz
Keyword(s):  
Proton Transport ◽  
Hydrogen Transfer ◽  
Atp Synthesis ◽  
Present Theory ◽  
Energy Transduction ◽  
Ion Concentration ◽  
Hydrogen Ions ◽  
Detailed Model ◽  
Hydrogen Ion Concentration

Energy transduction processes in biology are analyzed in terms of ordered chains of hydrogen bonds. The theory is an extension of studies on proton conductance in ice and is stimulated by current ideas on the role of hydrogen ions in oxidative phosphorylation and photophosphorylation. The possibility of a protochemistry paralleling electrochemistry is presented along with experimental evidence. The theory relating transmembrane electrochemical potential difference of hydrogen ion concentration to the synthesis of ATP is reviewed. The thermodynamics of hydrogen transfer across a membrane is treated including electrochemical and electromechanical factors. As a prelude to considering ATP synthesis, the acid-base dissociation reactions of ATP, ADP, and phosphate are analyzed. The thermodynamics of ATP synthesis is discussed and a detailed model is presented coupling the synthesis to proton transport. The model assumes a gated proton semiconductor that carries protons and allows them to interact specifically with well-defined substrate molecules. The physics of proton transport is outlined and various methods examined in the context of biological membranes. Emphasis is placed on solid-state proton semiconductors and the present theory of such structures is given. A section is included on possible biological applications of these semiconductors.

Thyroid Hormones and Mitochondria

2002 ◽  
Vol 22 (1) ◽  
pp. 17-32 ◽  
Author(s):  
Fernando Goglia ◽  
Elena Silvestri ◽  
Antonia Lanni
Keyword(s):  
Energy Metabolism ◽  
Thyroid Hormones ◽  
Uncoupling Protein ◽  
Atp Synthesis ◽  
Energy Transduction ◽  
Clear Cut ◽  
Expression Of Genes ◽  
Molecular Determinant ◽  
Mitochondrial Functions ◽  
Oxidative Processes

Because of their central role in the regulation of energy-transduction, mitochondria, the major site of oxidative processes within the cell, are considered a likely subcellular target for the action that thyroid hormones exert on energy metabolism. However, the mechanism underlying the regulation of basal metabolic rate (BMR) by thyroid hormones still remains unclear. It has been suggested that these hormones might uncouple substrate oxidation from ATP synthesis, but there are no clear-cut data to support this idea. Two iodothyronines have been identified as effectors of the actions of thyroid hormones on energy metabolism: 3',3,5-triiodo-L-thyronine (T3) and 3,5-diiodo-L-thyronine (T2). Both have significant effects on BMR, but their mechanisms of action are not identical. T3 acts on the nucleus to influence the expression of genes involved in the regulation of cellular metabolism and mitochondria function; 3,5-T2, on the other hand, acts by directly influencing the mitochondrial energy-transduction apparatus. A molecular determinant of the effects of T3 could be uncoupling protein-3 (UCP-3), while the cytochrome-c oxidase complex is a possible target for 3,5-T2. In conclusion, it is likely that iodothyronines regulate energy metabolism by both short-term and long-term mechanisms, and that they act in more than one way in affecting mitochondrial functions.

Sign in / Sign up

Export Citation Format

Share Document