INTRODUCTION The switch from quiescence (G0) into G1 and cell cycle progression critically depends on specific nutrients and metabolic capabilities. Conversely, metabolic networks are regulated by enzyme-metabolite interaction and transcriptional regulation that lead to flux modifications to support cell growth. How cells process and integrate environmental information into coordinated responses is challenging to analyse and not yet described quantitatively. OBJECTIVES To quantitatively monitor the central carbon metabolism during G0 exit and the first 2 h after reentering the cell cycle from synchronized Saccharomyces cerevisiae. METHODS Dynamic tailored 13C metabolic flux analysis was used to observe the intracellular metabolite flux changes, and the metabolome and proteome were observed to identify regulatory mechanisms. RESULTS G0 cells responded immediately to an extracellular increase of glucose. The intracellular metabolic flux changed in time and specific events were observed. High fluxes into trehalose and glycogen synthesis were observed during the G0 exit. Both fluxes then decreased, reaching a minimum at t = 65 min. Here, storage degradation contributed significantly (i.e. 21%) to the glycolytic flux. In contrast to these changes, the glucose uptake rate remained constant after the G0 exit. The flux into the oxidative pentose phosphate pathway was highest (29-fold increase, 36.4% of the glucose uptake) at t = 65 min, while it was very low at other time points. The maximum flux seems to correlate with a late G1 state preparing for the S phase transition. In the G1/S phase (t = 87 min), anaplerotic reactions such as glyoxylate shunt increased. Protein results show that during this transition, proteins belonging to clusters related with ribosome biogenesis and assembly, and initiation transcription factors clusters were continuously synthetised. CONCLUSION The intracellular flux distribution changes dynamically and these major rearrangements highlight the coordinate reorganization of metabolic flux to meet requirements for growth during different cell state.

中文翻译：

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在同步的酿酒酵母中，代谢物从静止转变为生长。

简介从静止（G0）到G1的转换以及细胞周期的进展关键取决于特定的营养物质和代谢能力。相反，代谢网络受酶-代谢物相互作用和转录调节的调节，从而导致通量修饰以支持细胞生长。细胞如何处理并将环境信息整合到协调的反应中是一项具有挑战性的分析工作，目前尚未进行定量描述。目的定量监测G0出口期间和从同步酿酒酵母重新进入细胞周期后的前2小时的中心碳代谢。方法采用动态量身定制的13C代谢通量分析方法观察细胞内代谢物通量的变化，并观察代谢组和蛋白质组以确定调节机制。结果G0细胞立即对细胞外葡萄糖增加作出反应。细胞内代谢通量随时间变化并且观察到特定事件。在G0出口期间观察到海藻糖和糖原合成的高通量。然后，两个通量均减小，在t = 65 min时达到最小值。在此，存储降解显着地贡献了糖酵解通量（21％）。与这些变化相反，G0退出后，葡萄糖摄取率保持恒定。在t = 65分钟时，进入氧化戊糖磷酸途径的通量最高（增加29倍，占葡萄糖吸收的36.4％），而在其他时间点则非常低。最大通量似乎与为S相转变做准备的晚期G1状态相关。在G1 / S阶段（t = 87分钟），诸如乙醛酸酯分流的异常反应增加。蛋白质结果显示，在此过渡过程中，连续合成了与核糖体生物发生和组装相关的簇以及起始转录因子簇。结论细胞内通量分布动态变化，这些主要的重排突出了代谢通量的坐标重组，以满足不同细胞状态下生长的需求。