Pietrobon D, Caplan S R
Biochemistry. 1985 Oct 8;24(21):5764-76. doi: 10.1021/bi00342a012.
General flow-force relations have been determined, by the Hill diagram method, for a six-state proton pump model with and without intrinsic uncoupling (molecular slipping). A computer-aided analysis of the resulting sigmoidal flow-force curves has been performed by using a set of physically meaningful rate constants. It is shown that gating effects and apparent irreversibility can arise from sigmoidicity. The regions of approximate linearity in the vicinity of inflection points, which may be far from equilibrium, have been examined with a view to characterization in terms of linear phenomenological equations, with due regard to the problems of kinetic equivalence of the forces and symmetry. The determination of thermodynamic parameters such as the degree of coupling, the phenomenological stoichiometry, and the efficiency in these regions is discussed, and their meaning is analyzed in relation to the parameters characterizing the Onsager domain close to equilibrium. The application of the phenomenological equations of near-equilibrium nonequilibrium thermodynamics to such regions is at best a simplification to be treated with great caution. A knowledge of the distance from equilibrium of the flow-controlling ranges of the forces (i.e., the ranges of approximate linearity) turns out to be crucial for the interpretation of thermodynamic parameters determined by manipulating one of the forces while the other remains constant, as well as for the interpretation of measurements of force ratios at static head. The latter approaches can give good estimates of the magnitude of the mechanistic stoichiometry and of the constant force if the pumps are highly coupled and are operating not far from equilibrium. The force-flow relationships are shown to be modified by intrinsic uncoupling, reflecting the regulatory influence of the forces on the extent and nature of the slip. Thus reaction slip increases, for example, as the force against which the proton pump operates increases. The possible physiological significance of regulated intrinsic uncoupling is discussed.
通过希尔图方法，已确定了具有和不具有内在解偶联（分子滑动）的六态质子泵模型的一般流量 - 力关系。利用一组具有物理意义的速率常数，对所得的S形流量 - 力曲线进行了计算机辅助分析。结果表明，S形特性可能导致门控效应和明显的不可逆性。已经研究了拐点附近可能远离平衡的近似线性区域，以便根据线性唯象方程进行表征，同时适当考虑力的动力学等效性和对称性问题。讨论了在这些区域中耦合度、唯象化学计量比和效率等热力学参数的确定，并分析了它们相对于表征接近平衡的昂萨格区域的参数的意义。将近平衡非平衡热力学的唯象方程应用于这些区域充其量只是一种需要极其谨慎对待的简化方法。事实证明，了解力的流量控制范围（即近似线性范围）与平衡的距离对于解释通过操纵一个力而另一个力保持恒定时确定的热力学参数，以及对于解释静水头下力比的测量结果至关重要。如果泵高度耦合且运行距离平衡不远，后一种方法可以很好地估计机械化学计量比的大小和恒定力。结果表明，内在解偶联会改变力 - 流量关系，反映了力对滑动程度和性质的调节影响。例如，随着质子泵运行所对抗的力增加，反应滑动会增加。讨论了调节内在解偶联可能的生理意义。
