Optimal Fluxes, Reaction Replaceability, and Response to Enzymopathies in the Human Red Blood Cell
Optimal Fluxes, Reaction Replaceability, and Response to Enzymopathies in the Human Red Blood Cell
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DOI：
10.1155/2010/415148
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发表时间：
2010-01-01
影响因子：
--
通讯作者：
Van Kerrebroeck, V.
中科院分区：
文献类型：
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作者：
De Martino, A.;Granata, D.;Van Kerrebroeck, V.
描述基因组尺度代谢网络的功能、关键依赖关系和对扰动的响应是一个具有重要应用的基本问题。一个关键的问题是确定潜在的最有害的反应敲除。将组合方法与采样技术相结合，探索可行通量状态的空间，可能为这一问题提供重要的见解。我们通过列举从底物到产物的替代途径，评估了人类红细胞中每一种代谢转化的可替代性，获得了单一酶病潜在损害的完整图谱。对健康细胞和突变细胞的最优稳态通量空间进行采样，揭示了拓扑和动力学方面的相关性和互补性。
Characterizing the capabilities, key dependencies, and response to perturbations of genome-scale metabolic networks is a basic problem with important applications. A key question concerns the identification of the potentially most harmful reaction knockouts. The integration of combinatorial methods with sampling techniques to explore the space of viable flux states may provide crucial insights on this issue. We assess the replaceability of every metabolic conversion in the human red blood cell by enumerating the alternative paths from substrate to product, obtaining a complete map of he potential damage of single enzymopathies. Sampling the space of optimal steady state fluxes in the healthy and in the mutated cell reveals both correlations and complementarity between topologic and dynamical aspects.