Ricard J, Soulié J M, Buc J, Bidaud M
Eur J Biochem. 1986 Sep 1;159(2):247-54. doi: 10.1111/j.1432-1033.1986.tb09860.x.
If the conformational transition involved in enzyme memory occurs in several elementary steps, the time constant of the overall 'slow' relaxation is mostly determined by the individual values of the rate constants pertaining to the overall transconformation. The extent of kinetic co-operativity of the enzyme reaction, however, is mostly controlled by the degree of reversibility of the elementary steps of the conformational transition. There is then no simple relation between the time scale of the 'slow' transition and the extent of kinetic co-operativity of the enzyme reaction. A slow transition of about 10(-3) s-1 is therefore perfectly compatible with a strong positive or negative co-operativity and in particular with the negative co-operativity observed with wheat germ hexokinase LI. The relationship that has been established recently [Pettersson, G. (1986) Eur. J. Biochem. 154, 167-170] between the 'slow' enzyme relaxation and the extent of kinetic co-operativity holds only in the specific case where the transconformation occurs in one step. Owing to the possible occurrence of a multistep conformation change, the lack of this relationship means nothing as to the validity, or the invalidity, of the concept of mnemonical transition. More informative than the time scale of the 'slow' transition is its dependence with respect to glucose and glucose 6-phosphate, which both react with the enzyme. The effect of reaction products on the modulation of kinetic co-operativity is also of cardinal importance in the diagnosis of enzyme memory. Since an alternative model has been recently proposed by Pettersson (cited above) to explain the mechanistic origin of kinetic co-operativity of monomeric enzymes, the effect of products on the kinetic co-operativity predicted by this alternative model has been studied theoretically, in order to determine whether it is consistent with the experimental results obtained with wheat germ hexokinase LI. This analysis shows that the predictions of this model are in total disagreement with both the predictions of the mnemonical model and the experimental results obtained with wheat germ hexokinase LI, as well as with other enzymes. This alternative model cannot therefore be considered as a sensible explanation of the mechanistic origin of co-operativity of monomeric enzymes. It is therefore concluded that the mnemonical model which rests on numerous experimental results, obtained by different research groups, on different enzymes is the simplest and most likely explanation of the kinetic subtleties displayed by some monomeric enzymes, and in particular wheat germ hexokinase LI.
如果酶记忆中涉及的构象转变发生在几个基本步骤中，那么整体“缓慢”弛豫的时间常数主要由与整体构象转变相关的速率常数的各个值决定。然而，酶反应的动力学协同程度主要由构象转变基本步骤的可逆程度控制。因此，“缓慢”转变的时间尺度与酶反应的动力学协同程度之间没有简单的关系。因此，约10⁻³ s⁻¹的缓慢转变与强正协同或负协同完全兼容，特别是与小麦胚芽己糖激酶LI所观察到的负协同兼容。最近[佩特松，G.（1986年）《欧洲生物化学杂志》154卷，167 - 170页]建立的“缓慢”酶弛豫与动力学协同程度之间的关系仅在构象转变发生在一步的特定情况下成立。由于可能发生多步构象变化，这种关系的缺乏对于记忆性转变概念的有效性或无效性并无意义。比“缓慢”转变的时间尺度更具信息量的是其对葡萄糖和葡萄糖6 - 磷酸的依赖性，这两者都与酶发生反应。反应产物对动力学协同调节的影响在酶记忆的诊断中也至关重要。由于佩特松（上文引用）最近提出了一个替代模型来解释单体酶动力学协同的机制起源，因此从理论上研究了产物对该替代模型预测的动力学协同的影响，以确定它是否与用小麦胚芽己糖激酶LI获得的实验结果一致。该分析表明，该模型的预测与记忆性模型的预测、用小麦胚芽己糖激酶LI获得的实验结果以及其他酶的实验结果完全不一致。因此，这个替代模型不能被视为对单体酶协同机制起源的合理解释。因此可以得出结论，基于不同研究小组在不同酶上获得的大量实验结果的记忆性模型是对一些单体酶，特别是小麦胚芽己糖激酶LI所表现出的动力学微妙之处的最简单且最有可能的解释。
