A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks

A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks
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DOI:
10.1038/73786
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发表时间:
2000-03-01
影响因子:
46.9
通讯作者:
Dandekar, T
Dandekar, T
中科院分区:
工程技术1区
文献类型:
--
作者:
Schuster, S;Fell, DA;Dandekar, T

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一组线性路径通常无法捕获代谢网络的全部行为。 “基本通量模式”的概念提供了一种数学工具来定义和全面描述一组酶在化学计量和热力学上可行的所有代谢途径。我们使用这个概念来分析磷酸戊糖途径(PPP)和糖酵解之间的相互作用。该系统的一组基本模式包括传统的糖酵解、无效循环、生物化学教科书中描述的所有 PPP 功能模式,以及先验地同样享有途径状态的其他模式。应用包括最大限度地提高氨基酸和抗生素合成中的产品产量、根据基因组数据重建代谢和一致性检查、酶缺陷分析以及代谢网络中的药物靶点识别。
A set of linear pathways often does not capture the full range of behaviors of a metabolic network. The concept of 'elementary flux modes' provides a mathematical tool to define and comprehensively describe all metabolic routes that are both stoichiometrically and thermodynamically feasible for a group of enzymes. We have used this concept to analyze the interplay between the pentose phosphate pathway (PPP) and glycolysis. The set of elementary modes for this system involves conventional glycolysis, a futile cycle, all the modes of PPP function described in biochemistry textbooks, and additional modes that are a priori equally entitled to pathway status. Applications include maximizing product yield in amino acid and antibiotic synthesis, reconstruction and consistency checks of metabolism from genome data, analysis of enzyme deficiencies, and drug target identification in metabolic networks.