Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Fukuoka, Japan.
Biomedical Informatics R&D Center, Kyushu Institute of Technology, Fukuoka, Japan.
Sci Rep. 2019 Nov 20;9(1):17139. doi: 10.1038/s41598-019-53589-1.
Many metabolic cycles, including the tricarboxylic acid cycle, glyoxylate cycle, Calvin cycle, urea cycle, coenzyme recycling, and substrate cycles, are well known to catabolize and anabolize different metabolites for efficient energy and mass conversion. In terms of stoichiometric structure, this study explicitly identifies two types of metabolic cycles. One is the well-known, elementary cycle that converts multiple substrates into different products and recycles one of the products as a substrate, where the recycled substrate is supplied from the outside to run the cycle. The other is the self-replenishment cycle that merges multiple substrates into two or multiple identical products and reuses one of the products as a substrate. The substrates are autonomously supplied within the cycle. This study first defines the self-replenishment cycles that many scientists have overlooked despite its functional importance. Theoretical analysis has revealed the design principle of the self-replenishment cycle that presents a threshold response without any bistability nor cooperativity. To verify the principle, three detailed kinetic models of self-replenishment cycles embedded in an E. coli metabolic system were simulated. They presented the threshold response or digital switch-like function that steeply shift metabolic status.
许多代谢循环，包括三羧酸循环、乙醛酸循环、卡尔文循环、尿素循环、辅酶循环和基质循环，都以高效的能量和物质转化为目的，对不同代谢物进行分解代谢和合成代谢。就计量结构而言，本研究明确识别了两种类型的代谢循环。一种是众所周知的基本循环，它将多种底物转化为不同的产物，并将其中一种产物循环作为底物再次使用，其中循环使用的底物是从外部提供的，以运行循环。另一种是自我补充循环，它将多种底物合并为两种或多种相同的产物，并将其中一种产物再次用作底物。底物在循环内自主供应。本研究首先定义了自我补充循环，尽管其功能重要，但许多科学家都忽略了这一点。理论分析揭示了自我补充循环的设计原则，它呈现出无双稳态或协同性的阈值响应。为了验证这一原则，模拟了三个嵌入大肠杆菌代谢系统的自我补充循环的详细动力学模型。它们呈现出阈值响应或数字开关样功能，使代谢状态急剧变化。
