Beyond aerobic glycolysis : Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis
Ralph J. DeBerardinis,Anthony A. Mancuso,Evgueni Daikhin,Ilana Nissim,Marc Yudkoff,Suzanne Wehrli,Craig B. Thompson +6 more
TLDR
Transformed cells exhibit a high rate of glutamine consumption that cannot be explained by the nitrogen demand imposed by nucleotide synthesis or maintenance of nonessential amino acid pools, and glutamine metabolism provides a carbon source that facilitates the cell's ability to use glucose-derived carbon and TCA cycle intermediates as biosynthetic precursors.Abstract:
Tumor cell proliferation requires rapid synthesis of macromolecules including lipids, proteins, and nucleotides. Many tumor cells exhibit rapid glucose consumption, with most of the glucose-derived carbon being secreted as lactate despite abundant oxygen availability (the Warburg effect). Here, we used 13C NMR spectroscopy to examine the metabolism of glioblastoma cells exhibiting aerobic glycolysis. In these cells, the tricarboxylic acid (TCA) cycle was active but was characterized by an efflux of substrates for use in biosynthetic pathways, particularly fatty acid synthesis. The success of this synthetic activity depends on activation of pathways to generate reductive power (NADPH) and to restore oxaloacetate for continued TCA cycle function (anaplerosis). Surprisingly, both these needs were met by a high rate of glutamine metabolism. First, conversion of glutamine to lactate (glutaminolysis) was rapid enough to produce sufficient NADPH to support fatty acid synthesis. Second, despite substantial mitochondrial pyruvate metabolism, pyruvate carboxylation was suppressed, and anaplerotic oxaloacetate was derived from glutamine. Glutamine catabolism was accompanied by secretion of alanine and ammonia, such that most of the amino groups from glutamine were lost from the cell rather than incorporated into other molecules. These data demonstrate that transformed cells exhibit a high rate of glutamine consumption that cannot be explained by the nitrogen demand imposed by nucleotide synthesis or maintenance of nonessential amino acid pools. Rather, glutamine metabolism provides a carbon source that facilitates the cell's ability to use glucose-derived carbon and TCA cycle intermediates as biosynthetic precursors.read more
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Quantitative Method to Investigate the Balance between Metabolism and Proteome Biomass: Starting from Glycine.
Haiwei Gu,Haiwei Gu,Patrick A. Carroll,Jianhai Du,Jiangjiang Zhu,Fausto Carnevale Neto,Robert N. Eisenman,Daniel Raftery,Daniel Raftery +8 more
TL;DR: A novel method to accurately determine the amounts of amino acids in various domains using serum, urine, and cell samples is demonstrated, which provides additional evidence that the metabolism of proliferating cells is adapted to facilitate producing new cells.
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Mitochondrial pyruvate carrier function and cancer metabolism.
TL;DR: Examination of recent findings on MPC function and cancer metabolism places special emphasis on the compartmentalization of pyruvate metabolism and the alternative routes of metabolism that maintain the cellular biosynthetic pools required for unrestrained proliferation in cancer.
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The glycerol backbone of phospholipids derives from noncarbohydrate precursors in starved lung cancer cells.
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TL;DR: It is reported that PEPCK-M–dependent glycerol phosphate formation from noncarbohydrate precursors (glyceroneogenesis) occurs in starved lung cancer cells and supports de novo glycerophospholipid synthesis.
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Tissue-resident NK cells differ in their expression profile of the nutrient transporters Glut1, CD98 and CD71.
Wilhelm Salzberger,Gloria Martrus,Kai Bachmann,Hanna Goebels,Leonard Heß,Martina Koch,Annika E. Langeneckert,Sebastian Lunemann,Karl J. Oldhafer,Caroline Pfeifer,Tobias Poch,Laura Richert,Christoph Schramm,Ramez Wahib,Madeleine J. Bunders,Marcus Altfeld +15 more
TL;DR: The results show that NK cells from peripheral blood differ from liver- and spleen-resident NK cells in the expression profile of nutrient transporters, consistent with a cell-adaptation to the different nutritional environment in these compartments.
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GRP78 enhances the glutamine metabolism to support cell survival from glucose deficiency by modulating the β-catenin signaling
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References
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