Quantitative Biomedicine Unit, BioCruces Health Research Institute, Barakaldo, Basque Country, Spain.
PLoS One. 2013;8(3):e58284. doi: 10.1371/journal.pone.0058284. Epub 2013 Mar 15.
The experimental observations and numerical studies with dissipative metabolic networks have shown that cellular enzymatic activity self-organizes spontaneously leading to the emergence of a Systemic Metabolic Structure in the cell, characterized by a set of different enzymatic reactions always locked into active states (metabolic core) while the rest of the catalytic processes are only intermittently active. This global metabolic structure was verified for Escherichia coli, Helicobacter pylori and Saccharomyces cerevisiae, and it seems to be a common key feature to all cellular organisms. In concordance with these observations, the cell can be considered a complex metabolic network which mainly integrates a large ensemble of self-organized multienzymatic complexes interconnected by substrate fluxes and regulatory signals, where multiple autonomous oscillatory and quasi-stationary catalytic patterns simultaneously emerge. The network adjusts the internal metabolic activities to the external change by means of flux plasticity and structural plasticity.
METHODOLOGY/PRINCIPAL FINDINGS: In order to research the systemic mechanisms involved in the regulation of the cellular enzymatic activity we have studied different catalytic activities of a dissipative metabolic network under different external stimuli. The emergent biochemical data have been analysed using statistical mechanic tools, studying some macroscopic properties such as the global information and the energy of the system. We have also obtained an equivalent Hopfield network using a Boltzmann machine. Our main result shows that the dissipative metabolic network can behave as an attractor metabolic network.
CONCLUSIONS/SIGNIFICANCE: We have found that the systemic enzymatic activities are governed by attractors with capacity to store functional metabolic patterns which can be correctly recovered from specific input stimuli. The network attractors regulate the catalytic patterns, modify the efficiency in the connection between the multienzymatic complexes, and stably retain these modifications. Here for the first time, we have introduced the general concept of attractor metabolic network, in which this dynamic behavior is observed.
耗散代谢网络的实验观察和数值研究表明，细胞酶活性会自发地自我组织，从而导致细胞中出现系统代谢结构，其特征是一组不同的酶反应始终处于活跃状态（代谢核心），而其余的催化过程仅间歇性地活跃。这种全局代谢结构已在大肠杆菌、幽门螺杆菌和酿酒酵母中得到验证，似乎是所有细胞生物的共同关键特征。与这些观察结果一致，细胞可以被视为一个复杂的代谢网络，它主要整合了大量自我组织的多酶复合物，这些复合物通过底物通量和调节信号相互连接，其中多个自主的振荡和准静态催化模式同时出现。网络通过通量可塑性和结构可塑性将内部代谢活动调整到外部变化。
方法/主要发现：为了研究细胞酶活性调节中涉及的系统机制，我们在不同的外部刺激下研究了耗散代谢网络的不同催化活性。使用统计力学工具分析了出现的生化数据，研究了一些宏观性质，如系统的全局信息和能量。我们还使用玻尔兹曼机获得了等效的霍普菲尔德网络。我们的主要结果表明，耗散代谢网络可以表现为吸引子代谢网络。
结论/意义：我们发现系统酶活性受具有存储功能代谢模式能力的吸引子控制，这些模式可以从特定的输入刺激中正确恢复。网络吸引子调节催化模式，改变多酶复合物之间的连接效率，并稳定保留这些修改。在这里，我们首次引入了吸引子代谢网络的一般概念，在这种网络中观察到了这种动态行为。
