Beg Q K, Vazquez A, Ernst J, de Menezes M A, Bar-Joseph Z, Barabási A-L, Oltvai Z N
Department of Pathology, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12663-8. doi: 10.1073/pnas.0609845104. Epub 2007 Jul 24.
The influence of the high intracellular concentration of macromolecules on cell physiology is increasingly appreciated, but its impact on system-level cellular functions remains poorly quantified. To assess its potential effect, here we develop a flux balance model of Escherichia coli cell metabolism that takes into account a systems-level constraint for the concentration of enzymes catalyzing the various metabolic reactions in the crowded cytoplasm. We demonstrate that the model's predictions for the relative maximum growth rate of wild-type and mutant E. coli cells in single substrate-limited media, and the sequence and mode of substrate uptake and utilization from a complex medium are in good agreement with subsequent experimental observations. These results suggest that molecular crowding represents a bound on the achievable functional states of a metabolic network, and they indicate that models incorporating this constraint can systematically identify alterations in cellular metabolism activated in response to environmental change.
细胞内大分子的高浓度对细胞生理的影响越来越受到重视，但其对系统水平细胞功能的影响仍缺乏充分量化。为评估其潜在效应，我们在此构建了一个大肠杆菌细胞代谢的通量平衡模型，该模型考虑了在拥挤细胞质中催化各种代谢反应的酶浓度的系统水平限制。我们证明，该模型对野生型和突变型大肠杆菌细胞在单一底物限制培养基中的相对最大生长速率，以及从复杂培养基中摄取和利用底物的顺序和模式的预测，与后续实验观察结果高度一致。这些结果表明，分子拥挤代表了代谢网络可实现功能状态的一种限制，并且表明纳入这一限制的模型能够系统地识别响应环境变化而激活的细胞代谢改变。
