Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada; Institute for Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
Biophys J. 2022 Jan 18;121(2):237-247. doi: 10.1016/j.bpj.2021.12.022. Epub 2021 Dec 22.
Metabolism is precisely coordinated, with the goal of balancing fluxes to maintain robust growth. However, coordinating fluxes requires information about rates, which can only be inferred through concentrations. While flux-sensitive metabolites have been reported, the design principles underlying such sensing have not been clearly elucidated. Here we use kinetic modeling to show that substrate concentrations of thermodynamically constrained reactions reflect upstream flux and therefore carry information about rates. Then we use untargeted multi-omic data from Escherichia coli and Saccharomyces cerevisiae to show that the concentrations of some metabolites in central carbon metabolism reflect fluxes as a result of thermodynamic constraints. We then establish, using 37 real concentration-flux relationships across both organisms, that in vivo ΔG≥-4 kJ/mol is the threshold above which substrates are likely to be sensitive to upstream flux(es).
代谢过程是精确协调的，其目标是平衡通量以维持稳健的生长。然而，协调通量需要有关速率的信息，而这些信息只能通过浓度来推断。虽然已经报道了通量敏感代谢物，但这种感应的设计原则尚未得到明确阐明。在这里，我们使用动力学建模表明，热力学受限反应的底物浓度反映了上游通量，因此携带有关速率的信息。然后，我们使用来自大肠杆菌和酿酒酵母的非靶向多组学数据表明，中心碳代谢中一些代谢物的浓度是由于热力学限制，反映了通量。然后，我们使用这两个生物体中的 37 个实际浓度-通量关系建立了一个模型，表明在体内ΔG≥-4 kJ/mol 是底物可能对上游通量敏感的阈值。
