Park Junyoung O, Rubin Sara A, Xu Yi-Fan, Amador-Noguez Daniel, Fan Jing, Shlomi Tomer, Rabinowitz Joshua D
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey, USA.
Nat Chem Biol. 2016 Jul;12(7):482-9. doi: 10.1038/nchembio.2077. Epub 2016 May 2.
In metabolism, available free energy is limited and must be divided across pathway steps to maintain a negative ΔG throughout. For each reaction, ΔG is log proportional both to a concentration ratio (reaction quotient to equilibrium constant) and to a flux ratio (backward to forward flux). Here we use isotope labeling to measure absolute metabolite concentrations and fluxes in Escherichia coli, yeast and a mammalian cell line. We then integrate this information to obtain a unified set of concentrations and ΔG for each organism. In glycolysis, we find that free energy is partitioned so as to mitigate unproductive backward fluxes associated with ΔG near zero. Across metabolism, we observe that absolute metabolite concentrations and ΔG are substantially conserved and that most substrate (but not inhibitor) concentrations exceed the associated enzyme binding site dissociation constant (Km or Ki). The observed conservation of metabolite concentrations is consistent with an evolutionary drive to utilize enzymes efficiently given thermodynamic and osmotic constraints.
在新陈代谢过程中，可用的自由能是有限的，必须在各个途径步骤之间进行分配，以始终保持负的ΔG。对于每个反应，ΔG与浓度比（反应商与平衡常数）以及通量比（逆向通量与正向通量）均呈对数比例关系。在这里，我们使用同位素标记来测量大肠杆菌、酵母和一种哺乳动物细胞系中的绝对代谢物浓度和通量。然后，我们整合这些信息，为每个生物体获得一组统一的浓度和ΔG。在糖酵解过程中，我们发现自由能的分配方式是为了减轻与接近零的ΔG相关的非生产性逆向通量。在整个新陈代谢过程中，我们观察到绝对代谢物浓度和ΔG基本保持不变，并且大多数底物（但不是抑制剂）浓度超过了相关酶结合位点的解离常数（Km或Ki）。观察到的代谢物浓度的保守性与在热力学和渗透限制条件下有效利用酶的进化驱动力是一致的。
