Department of Biochemistry and Molecular Biology, Complutense University, Madrid, Spain.
PLoS One. 2012;7(7):e41122. doi: 10.1371/journal.pone.0041122. Epub 2012 Jul 26.
Determining the regulation of metabolic networks at genome scale is a hard task. It has been hypothesized that biochemical pathways and metabolic networks might have undergone an evolutionary process of optimization with respect to several criteria over time. In this contribution, a multi-criteria approach has been used to optimize parameters for the allosteric regulation of enzymes in a model of a metabolic substrate-cycle. This has been carried out by calculating the Pareto set of optimal solutions according to two objectives: the proper direction of flux in a metabolic cycle and the energetic cost of applying the set of parameters. Different Pareto fronts have been calculated for eight different "environments" (specific time courses of end product concentrations). For each resulting front the so-called knee point is identified, which can be considered a preferred trade-off solution. Interestingly, the optimal control parameters corresponding to each of these points also lead to optimal behaviour in all the other environments. By calculating the average of the different parameter sets for the knee solutions more frequently found, a final and optimal consensus set of parameters can be obtained, which is an indication on the existence of a universal regulation mechanism for this system.The implications from such a universal regulatory switch are discussed in the framework of large metabolic networks.
确定基因组规模的代谢网络调控是一项艰巨的任务。有人假设，随着时间的推移，生化途径和代谢网络可能已经针对多个标准经历了一个优化的进化过程。在本研究中，使用多准则方法来优化代谢底物循环模型中酶的变构调节的参数。这是通过根据两个目标计算最优解的 Pareto 集来完成的：代谢循环中通量的适当方向和应用参数集的能量成本。针对八个不同的“环境”（特定的终产物浓度时程）计算了不同的 Pareto 前沿。对于每个得到的前沿，都确定了所谓的拐点，可以将其视为首选的权衡解决方案。有趣的是，与这些点中的每一个相对应的最佳控制参数也导致了所有其他环境中的最佳行为。通过计算更频繁出现的拐点的不同参数集的平均值，可以获得最终的最佳共识参数集，这表明该系统存在一种通用的调节机制。在大型代谢网络的框架下讨论了这种通用调节开关的意义。
