Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis

By Ralph J. Deberardinis, A. Mancuso, E. Daikhin, Ilana B. Nissim, M. Yudkoff, S. Wehrli, Craig B. Thompson. Proceedings of the National Academy of Sciences of the United States of America, 2007

2,564 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/9cd76b169a951e430c604b297061cbd807f540b7

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Citations in the corpus

Cancer cell metabolism: Warburg and beyond. (2008, background): “Recently, it has been demonstrated that glutamine may be metabolized by the citric acid cycle in cancer cells and converted into lactate, producing NADPH for lipid biosynthesis and oxaloacetate for replenishment of Krebs cycle intermediates (DeBerardinis et al., 2007).”
T cell metabolism drives immunity (2015, background): “2; DeBerardinis et al., 2007). cells proliferate (Ciofani and Zúñiga-Pflücker, 2005; Kelly et al., 2007).”
ESPEN guidelines on nutrition in cancer patients. (2017, background): “Glutamine levels drop in severe illness; however, it has not been proven that this is caused by glutamine depletion [250] On the other hand, tumour cells rapidly take up and metabolize glutamine [251] and it has been speculated that glutamine may contribute significantly to stabilizing the intracell”
Metabolomics and isotope tracing (2018, background): “For glutamine, it has revealed that, despite its dominant contribution to the TCA cycle in cultured cancer cells (DeBerardinis et al., 2007), it is a minority contributor for tumors in vivo (Hensley et al.”
Mitochondria and Cancer (2016, background): “This replenishment of the TCA cycle 4C units is termed anaplerosis and can occur through carboxylation of pyruvate or catabolism of glutamine and other amino acids (Comerford et al., 2014; DeBerardinis et al., 2007; Fan et al., 2009; Mashimo et al., 2014; Yuneva et al., 2007).”
The Warburg effect in tumor progression: Mitochondrial oxidative metabolism as an anti-metastasis mechanism (2014, background): “Since a considerable portion of observed oxygen consumption in cancer cells may be attributed to oxidation of alternate fuels such as glutamine [8], [9], the actual glucose oxidation in cancer cells is probably even lower.”
Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer (2009, background): “Glutaminolysis is a source of the electron donors NADPH, an important molecule required to satisfy the energy demands of cell proliferation [83].”
Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling (2013, positive): “Glutaminolysis is particularly important in proliferating cells in which TCA-cycle intermediates are continually depleted for use in biosynthetic reactions (DeBerardinis et al., 2007).”
KRAS: feeding pancreatic cancer proliferation (2014, neutral): “Glutamine can also provide a proliferating cell with a significant amount of NADPH through the activity of malic enzyme (ME1) which oxidatively decarboxylates malic acid, producing carbon dioxide, NADPH and pyruvate [45].”
Targeting Metabolism for Cancer Therapy (2017, background): “Glutamine is an important nitrogen donor for amino acids and nucleotides (Hosios et al., 2016), but glutamine uptake can exceed the nitrogen requirement of some cancer cells (DeBerardinis et al., 2007).”
Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis (2010, background): “…Kroemer and Pouyssegur, 2008), including those that regulate glycolysis (Christofk et al., 2008; Gatenby and Gillies, 2004), glutaminedependent anaplerosis (DeBerardinis et al., 2007, 2008a; Wise et al., 2008), and the production of lipids (DeBerardinis et al., 2008a; Menendez and Lupu, 2007).”
Q's next: The diverse functions of glutamine in metabolism, cell biology and cancer (2009, background): “In rapidly proliferating cultured glioblastoma cells, for example, most of the acetylCoA pool comes from glucose, whereas essentially all of the anaplerotic carbon (that is, the oxaloacetate) comes from glutamine (DeBerardinis et al., 2007).”
Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013, background): “Carbon-tracing experiments using proliferating glioblastoma cells have established that both glucose and glutamine contribute to mitochondrial citrate pools and subsequent lipid synthesis (69).”
The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation (2011, background): “Metabolic flux analysis in a glioblastoma cell line further revealed that a major portion of glutamine-derived nitrogen and carbon are incorporated into amino acids and lactate, a fraction of which are secreted as metabolic by-products (DeBerardinis et al., 2007).”