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Effect of macromolecular crowding on the kinetics of glycolytic enzymes and the behaviour of glycolysis in yeast
Integrative Biology ( IF 1.5 ) Pub Date : 2018-09-03 , DOI: 10.1039/c8ib00099a Henrik S. Thoke 1, 2, 3, 4 , Luis A. Bagatolli 5, 6, 7 , Lars F. Olsen 1, 2, 3, 4
Integrative Biology ( IF 1.5 ) Pub Date : 2018-09-03 , DOI: 10.1039/c8ib00099a Henrik S. Thoke 1, 2, 3, 4 , Luis A. Bagatolli 5, 6, 7 , Lars F. Olsen 1, 2, 3, 4
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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.
中文翻译：
大分子拥挤对酵母中糖酵解酶动力学和糖酵解行为的影响
水作为溶剂和反应物都参与了生物活性的所有方面。据推测，由于细胞中高浓度的大分子，细胞内的水处于高度结构化的状态，并且由于结合亲和力和变构规律的改变，这可能改变细胞内酶的活性。在这里，我们首先研究人为拥挤的水溶液中两种糖酵解酶的动力学，并表明拥挤确实改变了它们的动力学。根据我们的动力学测量，我们提出了一种振荡糖酵解的新模型，该模型代替了Michaelis–Menten或Monod–Wyman–Changeux动力学，使用了G. Ling在协会归纳（AI）假设框架内引入的Yang-Ling吸附等温线。 。使用这个模型，例如，（i）在代谢振荡期间，后一个变量与ATP活性同相振荡，并且（ii）糖酵解振荡的出现很大程度上取决于细胞在静止状态下细胞内水的偶极弛豫程度。我们的结果支持这样的观点，如AI假设所建议的，细胞内水偶极弛豫的程度受细胞质蛋白借助ATP极化细胞内水的能力的调节。该假设可能与许多其他生物振荡器的解释有关，包括细胞信号传导过程。
更新日期：2018-09-03
中文翻译：
大分子拥挤对酵母中糖酵解酶动力学和糖酵解行为的影响
水作为溶剂和反应物都参与了生物活性的所有方面。据推测，由于细胞中高浓度的大分子，细胞内的水处于高度结构化的状态，并且由于结合亲和力和变构规律的改变，这可能改变细胞内酶的活性。在这里，我们首先研究人为拥挤的水溶液中两种糖酵解酶的动力学，并表明拥挤确实改变了它们的动力学。根据我们的动力学测量，我们提出了一种振荡糖酵解的新模型，该模型代替了Michaelis–Menten或Monod–Wyman–Changeux动力学，使用了G. Ling在协会归纳（AI）假设框架内引入的Yang-Ling吸附等温线。 。使用这个模型，例如，（i）在代谢振荡期间，后一个变量与ATP活性同相振荡，并且（ii）糖酵解振荡的出现很大程度上取决于细胞在静止状态下细胞内水的偶极弛豫程度。我们的结果支持这样的观点，如AI假设所建议的，细胞内水偶极弛豫的程度受细胞质蛋白借助ATP极化细胞内水的能力的调节。该假设可能与许多其他生物振荡器的解释有关，包括细胞信号传导过程。
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