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Mol Syst Biol. 2017 November; 13(11): 953.
Published online 2017 November 9. doi:  10.15252/msb.20177763
PMCID: PMC5731346

Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle

Eunyong Ahn, 1 , Praveen Kumar, 2 , Dzmitry Mukha, 2 Amit Tzur, 3 , 4 and Tomer Shlomicorresponding author 1 , 2 , 5


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 LCMS‐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.

Keywords: cell cycle, cellular metabolism, isotope tracing, LCMS, metabolic flux analysis
Subject Categories: Cell Cycle, Genome-Scale & Integrative Biology, Metabolism

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Mol Syst Biol. (2017) 13: 953


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