Theory for the systemic definition of metabolic pathways and their use in interpreting metabolic function from? A pathway-oriented perspective
Theory for the systemic definition of metabolic pathways and their use in interpreting metabolic function from? A pathway-oriented perspective
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DOI：
10.1006/jtbi.2000.1073
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发表时间：
2000-04-07
影响因子：
2
通讯作者：
Palsson, BO
中科院分区：
文献类型：
--
作者：
Schilling, CH;Letscher, D;Palsson, BO
细胞代谢最常被描述和解释的生化反应，使代谢网络。基因组学正在为越来越多的生物体提供关于参与细胞代谢的基因/基因产物的近乎完整的信息。由于代谢系统的真正功能单元是其途径，因此，在全鳗鱼代谢的背景下定义代谢途径以分析代谢网络的结构设计和能力的时机已经到来。在这项研究中，我们提出了一套独特的系统独立的生化途径，称为极端途径，系统化学计量学和有限的热力学的基础上识别的理论基础。这些途径表示从凸分析导出的稳态通量锥的边缘，并且它们可以用于表示代谢网络可实现的任何通量分布。提出了一种算法来确定一组极端的路径为任何复杂的系统和分类方案介绍了这些途径的特征。系统的独立性的属性进行了讨论沿着与代谢调节和细胞代谢网络的演变相关的问题，其影响。从极端途径的集合中确定的潜在途径结构现在为我们提供了从基于途径的角度分析，解释和预测代谢功能的能力，除了传统的基于反应的角度。开发的算法和分类方案可用于描述注释基因组中的通路结构，以探索生物体的能力。(C)北京大学出版社.
Cellular metabolism is most often described and interpreted in terms of the biochemical reactions that make up the metabolic network. Genomics is providing near complete information regarding the genes/gene products participating in cellular metabolism for a growing number of organisms. As the true functional units of metabolic systems are its pathways, the time has arrived to define metabolic pathways in the context of whole-eel metabolism for the analysis of the structural design and capabilities of the metabolic network. In this study, we present the theoretical foundations for the identification of the unique set of systemically independent biochemical pathways, termed extreme pathways, based on system stochiometry and limited thermodynamics. These pathways represent the edges of the steady-state flux cone derived from convex analysis, and they can be used to represent any flux distribution achievable by the metabolic network. An algorithm is presented to determine the set of extreme pathways for a system of any complexity and a classification scheme is introduced for the characterization of these pathways. The property of systemic independence is discussed along with its implications for issues related to metabolic regulation and the evolution of cellular metabolic networks. The underlying pathway structure that is determined from the set of extreme pathways now provides us with the ability to analyse, interpret, and perhaps predict metabolic function from a pathway-based perspective in addition to the traditional reaction-based perspective. The algorithm and classification scheme developed can be used to describe the pathway structure in annotated genomes to explore the capabilities of an organism. (C) 2000 Academic Press.