Metabolite concentrations, fluxes and free energies imply efficient enzyme usage.
Metabolite concentrations, fluxes and free energies imply efficient enzyme usage.
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代谢物浓度，通量和自由能表示有效的酶使用。
DOI：
10.1038/nchembio.2077
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发表时间：
2016-07
影响因子：
14.8
通讯作者：
Rabinowitz JD
中科院分区：
文献类型：
--
作者：
Park JO;Rubin SA;Xu YF;Amador-Noguez D;Fan J;Shlomi T;Rabinowitz JD
在代谢中，可用的自由能是有限的，必须在途径步骤中分配，以保持ΔG始终为负。对于每个反应，ΔG与浓度比（反应常数与平衡常数）和通量比（反向通量与正向通量）都成对数比例。在这里，我们使用同位素标记来测量大肠杆菌，酵母和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，以获得一组统一的浓度和每个生物体的ΔG。在糖酵解中，我们发现自由能被分配，以减轻与ΔG接近零相关的非生产性反向通量。在整个代谢过程中，我们观察到绝对代谢物浓度和ΔG基本上是保守的，并且大多数底物（但不是抑制剂）浓度超过相关的酶结合位点亲和力。所观察到的代谢产物浓度的保守性与在热力学和渗透压约束下有效利用酶的进化驱动力是一致的。
In metabolism, available free energy is limited and must be divided across pathway steps to maintain ΔG negative 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 affinity. The observed conservation of metabolite concentrations is consistent with an evolutionary drive to utilize enzymes efficiently given thermodynamic and osmotic constraints.