Thoke Henrik S, Bagatolli Luis A, Olsen Lars F
Institute for Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK5230 Odense M, Denmark.
Integr Biol (Camb). 2018 Oct 15;10(10):587-597. doi: 10.1039/c8ib00099a.
Water is involved in all aspects of biological activity, both as a solvent and as a reactant. It is hypothesized that intracellular water is in a highly structured state due to the high concentrations of macromolecules in the cell and that this may change the activity of intracellular enzymes due to altered binding affinities and allosteric regulations. Here we first investigate the kinetics of two glycolytic enzymes in artificially crowded aqueous solutions and show that crowding does indeed change their kinetics. Based on our kinetic measurements we propose a new model of oscillating glycolysis that instead of Michaelis-Menten or Monod-Wyman-Changeux kinetics uses the Yang-Ling adsorption isotherm introduced by G. Ling in the frame of the Association-Induction (AI) hypothesis. Using this model, we can reproduce previous experimental observations of the coupling of glycolytic oscillations and intracellular water dynamics, e.g., (i) during the metabolic oscillations, the latter variable oscillates in phase with ATP activity, and (ii) the emergence of glycolytic oscillations largely depends on the extent of intracellular water dipolar relaxation in cells in the resting state. Our results support the view that the extent of intracellular water dipolar relaxation is regulated by the ability of cytoplasmic proteins to polarize intracellular water with the assistance of ATP, as suggested in the AI hypothesis. This hypothesis may be relevant to the interpretation of many other biological oscillators, including cell signalling processes.
水参与生物活性的各个方面，既是溶剂又是反应物。据推测，由于细胞内大分子浓度高，细胞内水处于高度结构化状态，这可能会因结合亲和力和别构调节的改变而改变细胞内酶的活性。在此，我们首先研究了两种糖酵解酶在人工拥挤水溶液中的动力学，结果表明拥挤确实会改变它们的动力学。基于我们的动力学测量，我们提出了一种新的振荡糖酵解模型，该模型不是使用米氏动力学或莫诺德-怀曼-尚热动力学，而是采用G. 凌在缔合诱导（AI）假说框架中引入的杨-凌吸附等温线。使用该模型，我们可以重现先前关于糖酵解振荡与细胞内水动力学耦合的实验观察结果，例如，（i）在代谢振荡期间，后一个变量与ATP活性同步振荡，以及（ii）糖酵解振荡的出现很大程度上取决于静息状态下细胞内水偶极弛豫的程度。我们的结果支持这样一种观点，即如AI假说中所提出的，细胞内水偶极弛豫的程度受细胞质蛋白在ATP协助下使细胞内水极化能力的调节。这一假说可能与许多其他生物振荡器的解释相关，包括细胞信号传导过程。
