Yang Feng, Qian Hong, Beard Daniel A
Biotechnology and Bioengineering Center, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Metab Eng. 2005 Jul;7(4):251-9. doi: 10.1016/j.ymben.2005.03.002.
Analysis of the stoichiometric structure of metabolic networks provides insights into the relationships between structure, function, and regulation of metabolic systems. Based on knowledge of only reaction stoichiometry, certain aspects of network functionality and robustness can be predicted. Current theories focus on breaking a metabolic network down into non-decomposable pathways able to operate in steady state. The physics underlying these theories is based on mass balance and the laws of thermodynamics. However, due to the inherent nonlinearity of the thermodynamic constraints on metabolic fluxes, computational analysis of large-scale biochemical systems can be expensive. In this study, it is shown how the feasible reaction directions may be determined by either computing the allowable ranges under the mass-balance and thermodynamic constraints or by analyzing the stoichiometric structure of the network. The computed reaction directions translate into a set of linear constraints necessary for thermodynamic feasibility. This set of necessary linear constraints is shown to be sufficient to guarantee feasibility in certain cases, thus translating the nonlinear thermodynamic constraints to linear. We show that for a reaction network of 44 internal reactions representing energy metabolism, the computed linear inequality constraints represent necessary and sufficient conditions for thermodynamic feasibility.
对代谢网络化学计量结构的分析有助于深入了解代谢系统的结构、功能和调控之间的关系。仅基于反应化学计量学知识，就可以预测网络功能和稳健性的某些方面。当前的理论侧重于将代谢网络分解为能够在稳态下运行的不可分解途径。这些理论背后的物理学基于质量平衡和热力学定律。然而，由于代谢通量热力学约束的固有非线性，大规模生化系统的计算分析可能成本高昂。在本研究中，展示了如何通过计算质量平衡和热力学约束下的允许范围或通过分析网络的化学计量结构来确定可行的反应方向。计算出的反应方向转化为热力学可行性所需的一组线性约束。在某些情况下，这组必要的线性约束被证明足以保证可行性，从而将非线性热力学约束转化为线性约束。我们表明，对于一个代表能量代谢的包含44个内部反应的反应网络，计算出的线性不等式约束代表了热力学可行性的必要和充分条件。
