Impact of the solvent capacity constraint on E. coli metabolism.
Impact of the solvent capacity constraint on E. coli metabolism.
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溶剂能力限制对大肠杆菌代谢的影响。
DOI：
10.1186/1752-0509-2-7
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发表时间：
2008-01-23
影响因子：
--
通讯作者：
Oltvai, Zoltan N.
中科院分区：
文献类型：
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作者：
Vazquez, Alexei;Beg, Qasim K.;deMenezes, Marcio A.;Ernst, Jason;Bar-Joseph, Ziv;Barabasi, Albert-Loszlo;Boros, Laszlo G.;Oltvai, Zoltan N.
获得细胞代谢活动的定量预测需要在生理生长条件下相关的物理化学约束的识别和建模。细胞质中的分子拥挤是这样一种潜在的限制，因为它限制了代谢酶可用的溶剂容量。使用最近引入的通量平衡建模框架（FBAwMC），我们在这里证明，这种约束决定了代谢开关在大肠杆菌。当它们从低生长速率转变到高生长速率时，这种转换的特征在于有效优化策略的改变、乙酸盐在高生长速率下的排泄以及E.大肠杆菌的代谢通量，后者被部分证实的中央代谢反应的通量测量。这些结果暗示了溶剂容量是作用于E.大肠杆菌细胞在高代谢速率下运行，并在它们从低生长速率转变为高生长速率时激活代谢开关。在快速生长的酵母细胞中观察到的需氧乙醇排泄（克拉布特里效应）和在快速分裂的癌细胞中观察到的需氧糖酵解（瓦尔堡效应）的背景下，这种限制的相关性应该在未来得到解决。
Obtaining quantitative predictions for cellular metabolic activities requires the identification and modeling of the physicochemical constraints that are relevant at physiological growth conditions. Molecular crowding in a cell's cytoplasm is one such potential constraint, as it limits the solvent capacity available to metabolic enzymes. Using a recently introduced flux balance modeling framework (FBAwMC) here we demonstrate that this constraint determines a metabolic switch in E. coli cells when they are shifted from low to high growth rates. The switch is characterized by a change in effective optimization strategy, the excretion of acetate at high growth rates, and a global reorganization of E. coli metabolic fluxes, the latter being partially confirmed by flux measurements of central metabolic reactions. These results implicate the solvent capacity as an important physiological constraint acting on E. coli cells operating at high metabolic rates and for the activation of a metabolic switch when they are shifted from low to high growth rates. The relevance of this constraint in the context of both the aerobic ethanol excretion seen in fast growing yeast cells (Crabtree effect) and the aerobic glycolysis observed in rapidly dividing cancer cells (Warburg effect) should be addressed in the future.
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影响因子：
3.4
作者：
Beard, DA;Liang, SC;Qian, H
通讯作者：
Qian, H
影响因子：
4
作者：
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通讯作者：
Minton, Allen P.
影响因子：
2.9
作者：
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通讯作者：
Kurland, IJ
影响因子：
5.6
作者：
ZIMMERMAN, SB;TRACH, SO
通讯作者：
TRACH, SO
影响因子：
9.9
作者：
通讯作者：
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