Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Biophys J. 2013 Mar 19;104(6):1380-90. doi: 10.1016/j.bpj.2013.01.056.
Complex networks of biochemical reactions, such as intracellular protein signaling pathways and genetic networks, are often conceptualized in terms of modules--semiindependent collections of components that perform a well-defined function and which may be incorporated in multiple pathways. However, due to sequestration of molecular messengers during interactions and other effects, collectively referred to as retroactivity, real biochemical systems do not exhibit perfect modularity. Biochemical signaling pathways can be insulated from impedance and competition effects, which inhibit modularity, through enzymatic futile cycles that consume energy, typically in the form of ATP. We hypothesize that better insulation necessarily requires higher energy consumption. We test this hypothesis through a combined theoretical and computational analysis of a simplified physical model of covalent cycles, using two innovative measures of insulation, as well as a possible new way to characterize optimal insulation through the balancing of these two measures in a Pareto sense. Our results indicate that indeed better insulation requires more energy. While insulation may facilitate evolution by enabling a modular plug-and-play interconnection architecture, allowing for the creation of new behaviors by adding targets to existing pathways, our work suggests that this potential benefit must be balanced against the metabolic costs of insulation necessarily incurred in not affecting the behavior of existing processes.
生化反应的复杂网络，如细胞内蛋白信号通路和遗传网络，通常被概念化为模块——半独立的组件集合，执行明确定义的功能，并且可以包含在多个通路中。然而，由于分子信使在相互作用和其他效应（统称为反效性）期间的隔离，真正的生化系统并不表现出完美的模块化。通过消耗能量（通常以 ATP 的形式）的酶促无效循环，生化信号通路可以免受抑制模块化的阻抗和竞争效应的影响。我们假设更好的隔离必然需要更高的能量消耗。我们通过对共价循环简化物理模型的理论和计算分析来检验这一假设，使用了两种创新的隔离度量方法，以及一种通过在帕累托意义上平衡这两种度量来表征最佳隔离的可能新方法。我们的结果表明，确实更好的隔离需要更多的能量。虽然隔离可能通过允许模块化的即插即用互连架构来促进进化，从而通过向现有通路添加目标来创建新的行为，但我们的工作表明，这种潜在的好处必须与隔离所必需的代谢成本相平衡，以避免对现有过程的行为产生影响。
