Metabolomics-driven quantitative analysis of ammonia assimilation in E. coli.
Metabolomics-driven quantitative analysis of ammonia assimilation in E. coli.
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DOI：
10.1038/msb.2009.60
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发表时间：
2009
影响因子：
9.9
通讯作者：
Rabinowitz, Joshua D.
中科院分区：
文献类型：
--
作者：
Yuan, Jie;Doucette, Christopher D.;Fowler, William U.;Feng, Xiao-Jiang;Piazza, Matthew;Rabitz, Herschel A.;Wingreen, Ned S.;Rabinowitz, Joshua D.
尽管对单个酶及其组织途径进行了广泛的研究，但酶网络控制细胞内代谢物浓度和通量的手段仍不完全清楚。在这里，我们通过代谢组学和基于常微分方程的模型研究了大肠杆菌中心氮代谢的综合调控。调节细胞外铵引发的代谢组变化集中在氮同化的两个关键中间体α-酮戊二酸和谷氨酰胺。许多其他化合物保持浓度稳态，表明在与营养扰动密切相关的代谢组子集中分离出浓度变化。与饱和酶对底物浓度不敏感的观点相反，对饱和酶活性位点的竞争被发现是酶通量的关键决定因素。结合控制谷氨酰胺合成酶活性的共价修饰反应，这种活性位点竞争足以解释和预测中心氮代谢产物复杂的动态响应模式。
Despite extensive study of individual enzymes and their organization into pathways, the means by which enzyme networks control metabolite concentrations and fluxes in cells remains incompletely understood. Here, we examine the integrated regulation of central nitrogen metabolism in Escherichia coli through metabolomics and ordinary-differential-equation-based modeling. Metabolome changes triggered by modulating extracellular ammonium centered around two key intermediates in nitrogen assimilation, α-ketoglutarate and glutamine. Many other compounds retained concentration homeostasis, indicating isolation of concentration changes within a subset of the metabolome closely linked to the nutrient perturbation. In contrast to the view that saturated enzymes are insensitive to substrate concentration, competition for the active sites of saturated enzymes was found to be a key determinant of enzyme fluxes. Combined with covalent modification reactions controlling glutamine synthetase activity, such active-site competition was sufficient to explain and predict the complex dynamic response patterns of central nitrogen metabolites.
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影响因子：
3.2
作者：
Atkinson, MR;Blauwkamp, TA;Ninfa, AJ
通讯作者：
Ninfa, AJ
影响因子：
14.8
作者：
Bennett, Bryson D.;Yuan, Jie;Rabinowitz, Joshua D.
通讯作者：
Rabinowitz, Joshua D.
影响因子：
3.2
作者：
GUTNICK, D;CALVO, JM;AMES, BN
通讯作者：
AMES, BN
DOI：
10.1073/pnas.97.18.10101
发表时间：
2000-08-29
影响因子：
11.1
作者：
Alter, O;Brown, PO;Botstein, D
通讯作者：
Botstein, D
影响因子：
2.9
作者：
Feng, Xiao-jiang;Rabitz, Herschel;Le Bris, Claude
通讯作者：
Le Bris, Claude