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On stability analysis of cascaded linear time varying systems in dynamic isotope experiments
AIChE Journal ( IF 3.7 ) Pub Date : 2020-02-05 , DOI: 10.1002/aic.16911
Weilu Lin 1 , Zejian Wang 1 , Mingzhi Huang 1 , Ju Chu 1 , Yingping Zhuang 1 , Siliang Zhang 1
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The dynamic 13C labeling experiment, as an emerging experimental technique, can be utilized to quantify intracellular fluxes of the cell culture under metabolic unsteady states conditions, for example, under fed batch mode. One main disadvantage of the current dynamic isotope experiment technique is that the intracellular metabolic pools have to be at pseudo‐steady state. Furthermore, to the best of our knowledge, the stability issue of dynamic isotope experiments is not addressed in the literature. In this work, if one assumes that concentrations of intracellular metabolites are nonsteady, it is shown that dynamic cumomer balance equations for any metabolic network are uniformly bounded‐input and bounded‐output stable regardless of the existence of traps. It is valid under very weak conditions. Specifically, it requires that the intracellular flux and the size of intracellular pool are finite and strictly greater than zero at any time. The new finding paves the way to utilize the dynamic isotope experiment to approximately quantify intracellular fluxes and sizes of intracellular pools under intracellular metabolic nonsteady state with piecewise affine fluxes.

中文翻译:

动态同位素实验中级联线性时变系统的稳定性分析

动态13作为一种新兴的实验技术,C标记实验可以用来量化在代谢不稳定状态下(例如在补料分批模式下)细胞培养的细胞内通量。当前动态同位素实验技术的主要缺点之一是细胞内代谢池必须处于伪稳态。此外,就我们所知,动态同位素实验的稳定性问题并未在文献中提及。在这项工作中,如果假设细胞内代谢物的浓度不稳定,则表明任何代谢网络的动态枯草平衡方程都是均匀的有界输入和有界输出稳定的,而不管是否存在陷阱。在非常弱的条件下有效。特别,它要求细胞内通量和细胞内池的大小必须是有限的,并且在任何时候都必须严格大于零。这一新发现为利用动态同位素实验在分段代谢仿射通量的细胞内代谢非稳态下近似定量细胞内通量和细胞内池大小铺平了道路。
更新日期:2020-02-05
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