Deberardinis, R. J. & Cheng, T. Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 29, 313-324

Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9063, USA.
Oncogene (Impact Factor: 8.46). 11/2009; 29(3):313-24. DOI: 10.1038/onc.2009.358
Source: PubMed


Several decades of research have sought to characterize tumor cell metabolism in the hope that tumor-specific activities can be exploited to treat cancer. Having originated from Warburg's seminal observation of aerobic glycolysis in tumor cells, most of this attention has focused on glucose metabolism. However, since the 1950s cancer biologists have also recognized the importance of glutamine (Q) as a tumor nutrient. Glutamine contributes to essentially every core metabolic task of proliferating tumor cells: it participates in bioenergetics, supports cell defenses against oxidative stress and complements glucose metabolism in the production of macromolecules. The interest in glutamine metabolism has been heightened further by the recent findings that c-myc controls glutamine uptake and degradation, and that glutamine itself exerts influence over a number of signaling pathways that contribute to tumor growth. These observations are stimulating a renewed effort to understand the regulation of glutamine metabolism in tumors and to develop strategies to target glutamine metabolism in cancer. In this study we review the protean roles of glutamine in cancer, both in the direct support of tumor growth and in mediating some of the complex effects on whole-body metabolism that are characteristic of tumor progression.

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    • "In growing cells, glutamine is converted to the TCA cycle intermediate a-ketoglutarate through the anaplerotic glutamate dehydrogenase pathway. Glutamine is also an essential nitrogen donor in the synthesis of other non-essential amino acids and nucleotides (DeBerardinis and Cheng, 2010). We noticed that activation of glutamine biosynthesis is essential for growth in sugar-feeding animals, suggesting that sugar and glutamine metabolisms are coupled to ensure proper growth rate. "
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    Cell Reports 10/2015; 13(13):1-15. DOI:10.1016/j.celrep.2015.08.081 · 8.36 Impact Factor
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    • "Due to the diversion of most glucose-derived intermediates to biosynthesis, glutamine uptake is also increased in tumours to replenish the depletion of TCA cycle intermediates which are normally supplied from glucose sources and to fuel mitochondrial ATP production. Additionally, recent work has shown that under certain conditions glutamine can also play another important role in the growth of tumour cells, providing acetyl-CoA for lipid synthesis through a process known as reductive carboxylation [35] [36] [37] [38]. Similar to glucose, the expression of membrane glutamine transporters (e.g., ASCT2), in particular the high affinity isoforms, is elevated in cancer [39]. "
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    • "Fluxes of these enzymes are commonly elevated in human cancers (Friday et al., 2011). Glutaminolysis also supports the production of molecules, such as glutathione and NADPH, which protect cells from oxidative stress (DeBerardinis and Cheng, 2010; Reitzer et al., 1979; Wise and Thompson, 2010). Mounting evidence suggests that many types of cancer cells have tumor-specific redox control alterations, with increased levels of reactive oxygen species (ROS) compared with normal cells (Kawanishi et al., 2006; Stuart et al., 2014; Szatrowski and Nathan, 1991; Toyokuni et al., 1995). "
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