Optimization-based metabolic control analysis.
Optimization-based metabolic control analysis.
复制标题
基于优化的代谢控制分析。
DOI：
10.1002/btpr.482
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发表时间：
2010
影响因子：
2.9
通讯作者：
Huang,Yinlun
中科院分区：
文献类型：
--
作者：
Uygun,Korkut;Uygun,Basak;Matthew,HowardWT;Huang,Yinlun
在这项工作中，一种新的基于优化的代谢控制分析（OMCA）方法，以减少代谢控制分析（MCA）的数据要求。假设使用最优控制方法，代谢网络中的通量与代谢物浓度和酶活性相关，作为相对于稳态目标最优的状态反馈控制系统。然后，它示出的最佳反馈增益直接相关的弹性系数（EC）的MCA。这种方法需要确定系统的代谢物和通量的相对"重要性"，与典型的MCA要求相比，这在显著减少实验数据的情况下是可能的。OMCA方法应用于肝细胞中糖酵解的自上而下的控制模型。统计表明，OMCA模型能够预测实验观察到的EC，很少有例外。此外，基于OMCA的模型协调研究表明，模型中四个假设的化学计量系数的修改可以解释大多数差异，除了相对于NADH/NAD比率的弹性。© 2010美国化学工程师学会生物技术。程序：2010
In this work, a novel optimization‐based metabolic control analysis (OMCA) method is introduced for reducing data requirement for metabolic control analysis (MCA). It is postulated that using the optimal control approach, the fluxes in a metabolic network are correlated to metabolite concentrations and enzyme activities as a state‐feedback control system that is optimal with respect to a homeostasis objective. It is then shown that the optimal feedback gains are directly related to the elasticity coefficients (ECs) of MCA. This approach requires determination of the relative “importance” of metabolites and fluxes for the system, which is possible with significantly reduced experimental data, as compared with typical MCA requirements. The OMCA approach is applied to a top–down control model of glycolysis in hepatocytes. It is statistically demonstrated that the OMCA model is capable of predicting the ECs observed experimentally with few exceptions. Further, an OMCA‐based model reconciliation study shows that the modification of four assumed stoichiometric coefficients in the model can explain most of the discrepancies, with the exception of elasticities with respect to the NADH/NAD ratio. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010