Coupling and biological free-energy transduction processes as a bridge between physics and life: Molecular-level instantiation of Ervin Bauer’s pioneering concepts in biological thermodynamics

Abstract

The nonequilibrium coupled processes of oxidation and ATP synthesis in the biological process of oxidative phosphorylation (OXPHOS) are fundamental to all life on our planet. These steady-state energy transduction processes ‒ coupled by proton and anion/counter-cation concentration gradients in the OXPHOS pathway ‒ generate ∼95 % of the ATP requirement of aerobic systems for cellular function. The rapid energy cycling and homeostasis of metabolites involved in this coupling are shown to be responsible for maintenance and regulation of stable nonequilibrium states, the latter first postulated in pioneering biothermodynamics work by Ervin Bauer between 1920 and 1935. How exactly does this occur? This is shown to be answered by molecular considerations arising from Nath’s torsional mechanism of ATP synthesis and two-ion theory of energy coupling developed in 25 years of research work on the subject. A fresh analysis of the biological thermodynamics of coupling that goes beyond the previous work of Stucki and others and shows how the system functions at the molecular level has been carried out. Thermodynamic parameters, such as the overall degree of coupling, q of the coupled system are evaluated for the state 4 to state 3 transition in animal mitochondria with succinate as substrate. The actual or operative P to O ratio, the efficiency of the coupled reactions, η, and the Gibbs energy dissipation, Φ have been calculated and shown to be in good agreement with experimental data. Novel mechanistic insights arising from the above have been discussed. A fourth law/principle of thermodynamics is formulated for a sub-class of physical and biological systems. The critical importance of constraints and time-varying boundary conditions for function and regulation is discussed in detail. Dynamic internal structural changes essential for torsional energy storage within the γ-subunit in a single molecule of the FOF1-ATP synthase and its transduction have been highlighted. These results provide a molecular-level instantiation of Ervin Bauer’s pioneering concepts in biological thermodynamics.