论文标题
代谢胰岛素信号传导的反应网络分析
Reaction Network Analysis of Metabolic Insulin Signaling
论文作者
论文摘要
绝对浓度鲁棒性(ACR)和一致性是化学反应网络理论中鲁棒性和稳定性理论中的新颖概念。在本文中,我们根据分解反应网络的最新进展将Shinar和Feinberg的反应网络分析方法扩展到了胰岛素信号系统。我们已经表明,具有20种,35个复合物和35个反应的网络是一致的,这意味着其每个化学计量兼容性类别中最多有一个正平衡。我们已经获得了该系统最好的独立分解,其中包括10个子网组成,其中揭示了三个子网,这些子网不仅在功能上而且在结构上很重要。利用网络面向缺陷的粗化,我们开发了一种确定整个网络正均衡的方法。我们的分析还表明,该系统的ACR中有8种来自缺陷零子网。有趣的是,我们已经表明,对于一组速率常数,胰岛素调节的葡萄糖转运蛋白glut4(在葡萄糖能量代谢中很重要)具有稳定的ACR。
Absolute concentration robustness (ACR) and concordance are novel concepts in the theory of robustness and stability within Chemical Reaction Network Theory. In this paper, we have extended Shinar and Feinberg's reaction network analysis approach to the insulin signaling system based on recent advances in decomposing reaction networks. We have shown that the network with 20 species, 35 complexes, and 35 reactions is concordant, implying at most one positive equilibrium in each of its stoichiometric compatibility class. We have obtained the system's finest independent decomposition consisting of 10 subnetworks, a coarsening of which reveals three subnetworks which are not only functionally but also structurally important. Utilizing the network's deficiency-oriented coarsening, we have developed a method to determine positive equilibria for the entire network. Our analysis has also shown that the system has ACR in 8 species all coming from a deficiency zero subnetwork. Interestingly, we have shown that, for a set of rate constants, the insulin-regulated glucose transporter GLUT4 (important in glucose energy metabolism), has stable ACR.