Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles
Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles
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DOI：
10.1371/journal.pcbi.1000319
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发表时间：
2009-03-01
影响因子：
4.3
通讯作者：
Savageau, Michael A.
中科院分区：
文献类型：
--
作者：
Coelho, Pedro M. B. M.;Salvador, Armindo;Savageau, Michael A.
尽管难以精确表征，但已广泛观察到微生物的耐用性。在正常运行状态的某个邻域内，性能可以保持几乎恒定，从而实现动态平衡，但在超出该邻域后，性能会突然崩溃，并产生病理后果。目前，还没有通用的方法来确定局部性能突然恶化的边界，这阻碍了对生物鲁棒性的分子基础的理解。在这里，我们介绍了一种通用的方法，用于表征操作制度之间的边界的基础上分段幂律表示系统的组件。这个概念框架允许我们将“全局公差”定义为参数的正常值与边界值之间的比值。我们说明了这一概念的实用程序的一类moiety-transfer周期，这是一个广泛的模块在生物学。我们的研究结果显示了一个区域的“最佳”的本地性能包围的“穷人”的地区，此外，选择改善本地性能往往推动操作值远离政权的边界，从而增加了全球的宽容。这些预测同意从还原烟酰胺腺嘌呤二核苷酸磷酸（NADPH）的人红细胞的氧化还原循环的实验数据。
Robustness of organisms is widely observed although difficult to precisely characterize. Performance can remain nearly constant within some neighborhood of the normal operating regime, leading to homeostasis, but then abruptly break down with pathological consequences beyond this neighborhood. Currently, there is no generic approach to identifying boundaries where local performance deteriorates abruptly, and this has hampered understanding of the molecular basis of biological robustness. Here we introduce a generic approach for characterizing boundaries between operational regimes based on the piecewise power-law representation of the system's components. This conceptual framework allows us to define "global tolerance'' as the ratio between the normal value of a parameter and the value at such a boundary. We illustrate the utility of this concept for a class of moiety-transfer cycles, which is a widespread module in biology. Our results show a region of "best'' local performance surrounded by "poor'' regions; also, selection for improved local performance often pushes the operating values away from regime boundaries, thus increasing global tolerance. These predictions agree with experimental data from the reduced nicotinamide adenine dinucleotide phosphate (NADPH) redox cycle of human erythrocytes.