Luo Ruo-Yu, Liao Sha, Tao Guan-Yang, Li Yuan-Yuan, Zeng Shaoqun, Li Yi-Xue, Luo Qingming
Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Mol Syst Biol. 2006;2:2006.0031. doi: 10.1038/msb4100071. Epub 2006 Jun 6.
To better understand the dynamic regulation of optimality in metabolic networks under perturbed conditions, we reconstruct the energetic-metabolic network in mammalian myocardia using dynamic flux balance analysis (DFBA). Additionally, we modified the optimal objective from the maximization of ATP production to the minimal fluctuation of the profile of metabolite concentration under ischemic conditions, extending the hypothesis of original minimization of metabolic adjustment to create a composite modeling approach called M-DFBA. The simulation results are more consistent with experimental data than are those of the DFBA model, particularly the retentive predominant contribution of fatty acid to oxidative ATP synthesis, the exact mechanism of which has not been elucidated and seems to be unpredictable by the DFBA model. These results suggest that the systemic states of metabolic networks do not always remain optimal, but may become suboptimal when a transient perturbation occurs. This finding supports the relevance of our hypothesis and could contribute to the further exploration of the underlying mechanism of dynamic regulation in metabolic networks.
为了更好地理解在受干扰条件下代谢网络中最优性的动态调节，我们使用动态通量平衡分析（DFBA）重建了哺乳动物心肌中的能量代谢网络。此外，我们将最优目标从最大化ATP生成修改为缺血条件下代谢物浓度分布的最小波动，扩展了原始代谢调节最小化的假设，从而创建了一种称为M-DFBA的复合建模方法。模拟结果比DFBA模型的结果更符合实验数据，特别是脂肪酸对氧化ATP合成的持续主要贡献，其确切机制尚未阐明，似乎也无法由DFBA模型预测。这些结果表明，代谢网络的系统状态并不总是保持最优，而是在发生短暂干扰时可能变得次优。这一发现支持了我们假设的相关性，并可能有助于进一步探索代谢网络中动态调节的潜在机制。
