University Lille, CNRS, UMR 8523 - PhLAM - Physique des Lasers Atomes et Molécules, Lille, France.
Biophys J. 2024 Oct 15;123(20):3600-3611. doi: 10.1016/j.bpj.2024.09.012. Epub 2024 Sep 14.
The transduction of free energy in metabolic networks represents a thermodynamic mechanism by which the free energy derived from nutrients is converted to drive nonspontaneous, energy-requiring metabolic reactions. This transduction is typically observed in processes that generate energy-rich molecules such as ATP and NAD(P)H, which, in turn, power specific reactions, particularly biosynthetic reactions. This property establishes a pivotal connection between the intricate topology of metabolic networks and their ability to redirect energy for functional purposes. The present study proposes a dedicated framework aimed at exploring the relationship between free-energy dissipation, network topology, and metabolic objectives. The starting point is that, regardless of the network topology, nonequilibrium chemostatting conditions impose stringent thermodynamic constraints on the feasible flux steady states to satisfy energy and entropy balances. An analysis of randomly sampled reaction networks shows that the network topology imposes additional constraints that restrict the accessible flux solution space, depending on key structural features such as the reaction's molecularity, reaction cycles, and conservation laws. Notably, topologies featuring multimolecular reactions that implement free-energy transduction mechanisms tend to extend the accessible flux domains, facilitating the achievement of metabolic objectives such as anabolic flux maximization or flux rerouting capacity. This approach is applied to a coarse-grained model of carbohydrate metabolism, highlighting the structural requirements for optimal biomass yield.
代谢网络中的自由能转导代表了一种热力学机制，通过该机制，可将营养物质中衍生的自由能转化为驱动力，推动非自发、需能的代谢反应。这种转导通常发生在产生高能分子（如 ATP 和 NAD(P)H）的过程中，高能分子继而为特定反应，特别是生物合成反应提供动力。这种特性在代谢网络的复杂拓扑结构与其将能量重新定向用于功能目的的能力之间建立了关键联系。本研究提出了一个专门的框架，旨在探索自由能耗散、网络拓扑和代谢目标之间的关系。研究的起点是，无论网络拓扑如何，非平衡恒化器条件对满足能量和熵平衡的可行通量稳态施加了严格的热力学限制。对随机采样的反应网络的分析表明，网络拓扑施加了额外的限制，根据关键结构特征（如反应的分子性、反应循环和守恒定律）限制了可访问的通量解空间。值得注意的是，具有实现自由能转导机制的多分子反应的拓扑结构往往会扩展可访问的通量区域，从而促进实现代谢目标，如最大化合成代谢通量或通量重定向能力。该方法应用于碳水化合物代谢的粗粒度模型，突出了最佳生物量产量的结构要求。
