Physik-Department, Technische Universität München, James-Franck-Straße 1, 85748 Garching, Germany.
J R Soc Interface. 2019 Jul 26;16(156):20190444. doi: 10.1098/rsif.2019.0444. Epub 2019 Jul 31.
Experimental observations suggest that cells change the intracellular localization of key enzymes to regulate the reaction fluxes in enzymatic networks. In particular, cells appear to use sequestration and co-clustering of enzymes as spatial regulation strategies. These strategies should be equally useful to achieve rapid flux regulation in synthetic biomolecular systems. Here, we leverage a theoretical model to analyse the capacity of enzyme sequestration and co-clustering to control the reaction flux in a branch of a reaction-diffusion network. We find that in both cases, the response of the system is determined by two dimensionless parameters, the ratio of total activities of the competing enzymes and the ratio of diffusion to reaction timescales. Using these dependencies, we determine the parameter range for which sequestration and co-clustering can yield a biologically significant regulatory effect. Based on the known kinetic parameters of enzymes, we conclude that sequestration and co-clustering represent a viable regulation strategy for a large fraction of metabolic enzymes, and suggest design principles for reaction flux regulation in natural or synthetic systems.
实验观察表明，细胞会改变关键酶的细胞内定位，以调节酶网络中的反应通量。特别是，细胞似乎将酶的隔离和共聚类作为空间调节策略。这些策略在合成生物分子系统中实现快速通量调节也应该同样有用。在这里，我们利用一个理论模型来分析酶隔离和共聚类在反应扩散网络分支中控制反应通量的能力。我们发现，在这两种情况下，系统的响应都由两个无量纲参数决定，即竞争酶的总活性比和扩散与反应时间尺度比。利用这些依赖性，我们确定了隔离和共聚类可以产生生物学显著调节效果的参数范围。基于酶的已知动力学参数，我们得出结论，隔离和共聚类代表了代谢酶的很大一部分可行的调节策略，并为自然或合成系统中的反应通量调节提出了设计原则。
