Elucidation and structural analysis of conserved pools for genome-scale metabolic reconstructions
Elucidation and structural analysis of conserved pools for genome-scale metabolic reconstructions
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DOI：
10.1529/biophysj.104.043489
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发表时间：
2005-01-01
影响因子：
3.4
通讯作者：
Maranas, CD
中科院分区：
文献类型：
--
作者：
Nikolaev, EV;Burgard, AP;Maranas, CD
在这篇文章中，我们引入代谢物浓度耦合分析（MCCA）来研究基因组尺度代谢网络中代谢物浓度的保守关系。该分析允许在全球范围内识别其浓度始终在共同保守池内耦合的代谢物子集。此外，最小保守池识别（MCPI）的程序开发，阐明保守池的目标代谢产物，而无需计算整个基础的保守关系。这些方法在幽门螺杆菌、大肠杆菌和酿酒酵母的基因组规模的代谢重建上得到了证明。尽管所检查的生物体的模型的大小和复杂性的显着差异，我们发现，几乎所有的代谢物的浓度耦合在一个相对较少的子集。这些对应于碳分子进出网络的整体交换，能量和氧化还原辅因子的相互转化，以及代谢物之间氮、硫、磷酸盐、辅酶A和酰基载体蛋白部分的转移。大型保守库的存在可以被视为保护细胞系统免受应激的全球生物物理屏障，维持关键代谢物之间的协调相互转化，并提供全球代谢调节的额外模式。因此，开发的方法提供了新的和通用的工具，用于阐明代谢物浓度之间的耦合关系，在生物技术和医学应用的影响。
In this article, we introduce metabolite concentration coupling analysis ( MCCA) to study conservation relationships for metabolite concentrations in genome-scale metabolic networks. The analysis allows the global identification of subsets of metabolites whose concentrations are always coupled within common conserved pools. Also, the minimal conserved pool identification ( MCPI) procedure is developed for elucidating conserved pools for targeted metabolites without computing the entire basis conservation relationships. The approaches are demonstrated on genome-scale metabolic reconstructions of Helicobacter pylori, Escherichia coli, and Saccharomyces cerevisiae. Despite significant differences in the size and complexity of the examined organism's models, we find that the concentrations of nearly all metabolites are coupled within a relatively small number of subsets. These correspond to the overall exchange of carbon molecules into and out of the networks, interconversion of energy and redox cofactors, and the transfer of nitrogen, sulfur, phosphate, coenzyme A, and acyl carrier protein moieties among metabolites. The presence of large conserved pools can be viewed as global biophysical barriers protecting cellular systems from stresses, maintaining coordinated interconversions between key metabolites, and providing an additional mode of global metabolic regulation. The developed approaches thus provide novel and versatile tools for elucidating coupling relationships between metabolite concentrations with implications in biotechnological and medical applications.