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A facilitated diffusion model constrained by the probability isotherm: a pedagogical exercise in intuitive non-equilibrium thermodynamics

机译:受概率等温线约束的简化扩散模型:直观非平衡热力学中的教学法练习

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摘要

This paper seeks to develop a more thermodynamically sound pedagogy for students of biological transport than is currently available from either of the competing schools of linear non-equilibrium thermodynamics (LNET) or Michaelis–Menten kinetics (MMK). To this end, a minimal model of facilitated diffusion was constructed comprising four reversible steps: cis-substrate binding, cis→trans bound enzyme shuttling, trans-substrate dissociation and trans→cis free enzyme shuttling. All model parameters were subject to the second law constraint of the probability isotherm, which determined the unidirectional and net rates for each step and for the overall reaction through the law of mass action. Rapid equilibration scenarios require sensitive ‘tuning’ of the thermodynamic binding parameters to the equilibrium substrate concentration. All non-equilibrium scenarios show sigmoidal force–flux relations, with only a minority of cases having their quasi-linear portions close to equilibrium. Few cases fulfil the expectations of MMK relating reaction rates to enzyme saturation. This new approach illuminates and extends the concept of rate-limiting steps by focusing on the free energy dissipation associated with each reaction step and thereby deducing its respective relative chemical impedance. The crucial importance of an enzyme's being thermodynamically ‘tuned’ to its particular task, dependent on the cis- and trans-substrate concentrations with which it deals, is consistent with the occurrence of numerous isoforms for enzymes that transport a given substrate in physiologically different circumstances. This approach to kinetic modelling, being aligned with neither MMK nor LNET, is best described as intuitive non-equilibrium thermodynamics, and is recommended as a useful adjunct to the design and interpretation of experiments in biotransport.
机译:本文旨在为生物运输学的学生开发一种比现有的线性非平衡热力学(LNET)或迈克尔尼斯-门腾动力学(MMK)竞争学校更热力学的教学法。为此,构建了包括四个可逆步骤的促进扩散的最小模型:顺式-底物结合,顺式→反式结合酶穿梭,反式-底物解离和反式→顺式游离酶穿梭。所有模型参数都受概率等温线的第二定律约束,该定律确定了每个步骤的单向速率和净速率,并通过质量作用定律确定了整体反应的速率。快速平衡方案要求将热力学结合参数“平衡”到平衡底物浓度。所有非平衡情况都显示出S形力-通量关系,只有少数情况的准线性部分接近平衡。很少有案例能够满足将反应速率与酶饱和相关的MMK预期。通过关注与每个反应步骤相关的自由能耗散,并由此推导了其各自的相对化学阻抗,这种新方法阐明并扩展了限速步骤的概念。根据酶所处理的顺式和反式底物浓度,将酶热力学“调节”至其特定任务的至关重要,这与在生理上不同情况下转运给定底物的酶的多种同工型的发生一致。这种与MMK或LNET都不匹配的动力学建模方法,最好被描述为直观的非平衡热力学,并被推荐作为生物运输实验设计和解释的有用辅助手段。

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