Trade-off of dynamic fragility but not of robustness in metabolic pathways in silico
Trade-off of dynamic fragility but not of robustness in metabolic pathways in silico
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DOI：
10.1111/febs.12057
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发表时间：
2013-01-01
期刊：
影响因子：
5.4
通讯作者：
Westerhoff, Hans V.
中科院分区：
文献类型：
--
作者：
Quinton-Tulloch, Mark J.;Bruggeman, Frank J.;Westerhoff, Hans V.
选择鲁棒性是生化网络的一个关键特征。它赋予生活在动态环境中的生物体以健身益处。网络对外部扰动的（不）敏感性是由网络动力学、结构和酶动力学之间的相互作用引起的。在这项工作中，我们专注于鲁棒性和控制（脆弱性）之间的微妙相互作用。我们描述了一个定量的方法来定义系统通量的脆弱性和鲁棒性的扰动。我们发现，对于许多数学模型的代谢途径，鲁棒性的通量相对于所有的酶活性的扰动被捕获的鲁棒性系数的广泛分布。我们发现，在代谢途径通量相对于特定网络步骤的扰动不太鲁棒的情况下，平均鲁棒性仍然可以增加。然后，我们表明，脆弱性是保守的网络过程的扰动和等同的脆弱性与代谢控制分析中定义的控制。这突出了脆弱性和鲁棒性之间相互作用的非直观性质，以及对动态网络理解的需要。
Selective robustness is a key feature of biochemical networks. It confers a fitness benefit to organisms living in dynamic environments. The (in-)sensitivity of a network to external perturbations results from the interplay between network dynamics, structure and enzyme kinetics. In this work, we focus on the subtle interplay between robustness and control (fragility). We describe a quantitative method for defining the fragility and robustness of system fluxes to perturbations. We find that for many mathematical models of metabolic pathways, the robustness of fluxes vis-a-vis perturbations of all the enzyme activities is captured by a broad distribution of the robustness coefficients. We find that in cases where a metabolic pathway flux is made less robust with respect to the perturbation of a particular network step, the average robustness may still be increased. We then show that fragility is conserved upon a perturbation of network processes and equate fragility with control as defined in metabolic control analysis. This highlights the non-intuitive nature of the interplay between fragility and robustness and the need for a dynamic network understanding.