Chun P W
Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville 32610-0245, USA.
Cell Biochem Biophys. 2000;33(2):149-69. doi: 10.1385/CBB:33:2:149.
It is known that most living systems can live and operate optimally only at a sharply defined temperature, or over a limited temperature range, at best, which implies that many basic biochemical interactions exhibit a well-defined Gibbs free energy minimum as a function of temperature. The Gibbs free energy change, deltaG(o) (T), for biological systems shows a complicated behavior, in which deltaG(o)(T) changes from positive to negative, then reaches a negative value of maximum magnitude (favorable), and finally becomes positive as temperature increases. The critical factor in this complicated thermodynamic behavior is a temperature-dependent heat capacity change (deltaCp(o)(T) of reaction, which is positive at low temperature, but switches to a negative value at a temperature well below the ambient range. Thus, the thermodynamic molecular switch determines the behavior patterns of the Gibbs free energy change, and hence a change in the equilibrium constant, Keq, and/or spontaneity. The subsequent, mathematically predictable changes in deltaH(o)(T), deltaS(o)(T), deltaW(o)(T), and deltaG(o)(T) give rise to the classically observed behavior patterns in biological reactivity, as demonstrated in three interacting protein systems: the acid dimerization reaction of alpha-chymotrypsin at low pH, interaction of chromogranin A with the intraluminal loop peptide of the inositol 1,4,5-triphosphate receptor at pH 5.5, and the binding of L-arabinose and D-galactose to the L-arabinose binding protein of Escherichia coli. In cases of protein unfolding of four mutants of phage T4 lysozyme, no thermodynamic molecular switch is observed.
众所周知，大多数生命系统只有在严格限定的温度下，或者至多在有限的温度范围内，才能最佳地生存和运作，这意味着许多基本的生化相互作用表现出作为温度函数的明确的吉布斯自由能最小值。生物系统的吉布斯自由能变化ΔG⁰(T)呈现出复杂的行为，其中ΔG⁰(T)从正值变为负值，然后达到最大幅度的负值（有利），最后随着温度升高变为正值。这种复杂热力学行为的关键因素是与温度相关的反应热容量变化（ΔCₚ⁰(T)），它在低温下为正，但在远低于环境范围的温度下变为负值。因此，热力学分子开关决定了吉布斯自由能变化的行为模式，进而决定了平衡常数Kₑq和/或自发性的变化。随后，ΔH⁰(T)、ΔS⁰(T)、ΔW⁰(T)和ΔG⁰(T)在数学上可预测的变化导致了生物学反应性中经典观察到的行为模式，这在三个相互作用的蛋白质系统中得到了证明：低pH下α-胰凝乳蛋白酶的酸二聚化反应、pH 5.5时嗜铬粒蛋白A与肌醇1,4,5-三磷酸受体腔内环肽的相互作用，以及L-阿拉伯糖和D-半乳糖与大肠杆菌L-阿拉伯糖结合蛋白的结合。在噬菌体T4溶菌酶四个突变体的蛋白质解折叠情况下，未观察到热力学分子开关。
