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.
摘要:
氧化磷酸化(OXPHOS)生物过程中氧化和ATP合成的非平衡耦合过程是我们星球上所有生命的基础。这些稳态的能量转导过程-通过OXPHOS途径中的质子和阴离子/抗衡阳离子浓度梯度耦合-产生有氧系统对细胞功能的ATP需求的95%。参与这种偶联的代谢物的快速能量循环和稳态被证明是维持和调节稳定非平衡状态的原因。后者在1920年至1935年之间由ErvinBauer进行的开创性生物热力学工作中首次提出。这到底是如何发生的?这可以通过Nath的ATP合成扭转机制和在25年的研究工作中发展起来的两离子能量耦合理论引起的分子考虑来回答。对偶联的生物热力学进行了新的分析,该分析超出了Stucki和其他人的先前工作,并显示了该系统在分子水平上的功能。热力学参数,例如整体耦合程度,在以琥珀酸作为底物的动物线粒体中评估偶联系统的q的状态4至状态3转变。实际或有效的P-O比,偶联反应的效率,η,和吉布斯的能量耗散,Φ已被计算并显示与实验数据非常吻合。已经讨论了由上述引起的新的机械见解。已经强调了动态内部结构变化,这些变化对于FOF1-ATP合酶的单个分子中γ-亚基内的扭转能储存及其转导至关重要。这些结果提供了ErvinBauer在生物热力学中的开创性概念的分子水平实例化。