Cellular metabolic demands change throughout the cell cycle. Nevertheless, a characterization of how metabolic fluxes adapt to the changing demands throughout the cell cycle is lacking. Here, we developed a temporal-fluxomics approach to derive a comprehensive and quantitative view of alterations in metabolic fluxes throughout the mammalian cell cycle. This is achieved by combining pulse-chase LC-MS-based isotope tracing in synchronized cell populations with computational deconvolution and metabolic flux modeling. We find that TCA cycle fluxes are rewired as cells progress through the cell cycle with complementary oscillations of glucose versus glutamine-derived fluxes: Oxidation of glucose-derived flux peaks in late G1 phase, while oxidative and reductive glutamine metabolism dominates S phase. These complementary flux oscillations maintain a constant production rate of reducing equivalents and oxidative phosphorylation flux throughout the cell cycle. The shift from glucose to glutamine oxidation in S phase plays an important role in cell cycle progression and cell proliferation.

中文翻译：

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时间通量组学揭示了整个哺乳动物细胞周期中TCA周期通量的振荡。

在整个细胞周期中，细胞代谢需求发生变化。然而，缺乏表征代谢通量如何适应整个细胞周期内不断变化的需求的特征。在这里，我们开发了一种时间流线型方法，以得出关于整个哺乳动物细胞周期中代谢通量变化的全面和定量的观点。这是通过将同步细胞群体中基于脉冲追踪LC-MS的同位素示踪与计算解卷积和代谢通量建模相结合而实现的。我们发现，随着细胞与葡萄糖和谷氨酰胺衍生的通量的互补振荡，随着细胞的发展，TCA循环通量被重新连接：G1期后期葡萄糖衍生的通量峰的氧化，而氧化和还原性谷氨酰胺代谢占主导。这些互补的通量振荡在整个细胞周期中保持恒定的还原当量和氧化磷酸化通量的生产率。在S期中，从葡萄糖到谷氨酰胺氧化的转变在细胞周期进程和细胞增殖中起重要作用。