From the Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina 27710
J Biol Chem. 2018 Dec 21;293(51):19725-19739. doi: 10.1074/jbc.RA118.004372. Epub 2018 Oct 25.
Nutrition and metabolism are fundamental to cellular function. Metabolic activity ( rates of flow, most commonly referred to as flux) is constrained by thermodynamics and regulated by the activity of enzymes. The general principles that relate biological and physical variables to metabolic control are incompletely understood. Using metabolic control analysis and computer simulations in several models of simplified metabolic pathways, we derive analytical expressions that define relationships between thermodynamics, enzyme activity, and flux control. The relationships are further analyzed in a mathematical model of glycolysis as an example of a complex biochemical pathway. We show that metabolic pathways that are very far from equilibrium are controlled by the activity of upstream enzymes. However, in general, regulation of metabolic fluxes by an enzyme has a more adaptable pattern, which relies more on distribution of free energy among reaction steps in the pathway than on the thermodynamic properties of the given enzyme. These findings show how the control of metabolic pathways is shaped by thermodynamic constraints of the given pathway.
营养和代谢是细胞功能的基础。代谢活动（流动速率，通常称为通量）受到热力学的限制，并受酶活性的调节。将生物和物理变量与代谢控制相关联的一般原则尚未完全理解。我们使用简化代谢途径的几种模型中的代谢控制分析和计算机模拟，推导出定义热力学、酶活性和通量控制之间关系的分析表达式。这些关系在糖酵解的数学模型中进一步进行了分析，作为复杂生化途径的一个例子。我们表明，远离平衡的代谢途径受到上游酶活性的控制。然而，一般来说，酶对代谢通量的调节具有更具适应性的模式，它更多地依赖于途径中反应步骤之间自由能的分布，而不是给定酶的热力学性质。这些发现表明代谢途径的控制是如何受到给定途径热力学限制的影响的。
