ArticleNature communications2019
Coordinative metabolism of glutamine carbon and nitrogen in proliferating cancer cells under hypoxia.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
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Who cites it
153 citing papers in PubMed, 224 citations in OpenAlex.
- Real-time NMR analysis of glutamine metabolism for screening anti-cancer agents in living cells.Magnetic resonance letters · 2027Article
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- Nicotinamide nucleotide transhydrogenase directly couples redox homeostasis to proline biosynthesis in human glioma.Molecular cell · 2026Article
- Metabolic circuitry of NADH buffering reveals a vulnerability in redox-adaptive cancer cells.Innovation (Cambridge (Mass.)) · 2026Article
- Glutamine Metabolism in Cardiac Hypertrophy.Reviews in cardiovascular medicine · 2026Review
- Lactate-dependent regulation of ferroptosis: redox homeostasis, lactylation, and translational perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- Preliminary clinical investigation ofEuropean journal of nuclear medicine and molecular imaging · 2026Article
- HIF-1α drives distinct aspects of hypoxia-induced glucose metabolism in intestinal epithelial cells.The Journal of biological chemistry · 2026Article
- Mycobacterium tuberculosis MEM39 (Rv1977) hijacks host aldolase A (ALDOA) to subvert immunometabolism to facilitate bacterial intracellular survival.Cellular & molecular immunology · 2026Article
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Identification of oral squamous cell carcinoma by an electronic nose based on an array of metal oxide sensors with machine learning.BMC oral health · 2026Article
- The hidden players: LncRNA-Encoded micropeptides in cancer hallmarks.Cellular and molecular life sciences : CMLS · 2026Review
- Application of untargeted plasma metabolomics and machine learning to construct a diagnostic model for hypertrophic cardiomyopathy: a case-control study.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Perfluorooctanoic Acid Exposure Causes Macrophage Ammonia Retention and Induces Spontaneous Miscarriages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated analysis of glutamine metabolism and immune microenvironment identifies GOT2 as a prognostic gene in head and neck squamous cell carcinoma.Discover oncology · 2026Article
- Advances in plasma metabolomics detection technology and its clinical applications in lung cancer and other malignancies.Holistic integrative oncology. · 2026Review
- Unraveling autophagy-metabolism crosstalk in cancer: Molecular insights and therapeutic strategies.Theranostics · 2026Review
- From mechanisms to management: a comprehensive review of sarcopenia in gastric cancer.Frontiers in nutrition · 2026Review
- Ammonia signaling network: the intersection of tumor metabolism, epigenetics, and metastasis.Frontiers in endocrinology · 2026Review
- Glutamine Metabolism: Role in Cancer Cell Proliferation and Survival.Cancer treatment and research · 2026Review
93 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Under hypoxia, most of glucose is converted to secretory lactate, which leads to the overuse of glutamine-carbon. However, under such a condition how glutamine nitrogen is disposed to avoid over-accumulating ammonia remains to be determined. Here we identify a metabolic flux of glutamine to secretory dihydroorotate, which is indispensable to glutamine-carbon metabolism under hypoxia. We found that glutamine nitrogen is necessary to nucleotide biosynthesis, but enriched in dihyroorotate and orotate rather than processing to its downstream uridine monophosphate under hypoxia. Dihyroorotate, not orotate, is then secreted out of cells. Furthermore, we found that the specific metabolic pathway occurs in vivo and is required for tumor growth. The identified metabolic pathway renders glutamine mainly to acetyl coenzyme A for lipogenesis, with the rest carbon and nitrogen being safely removed. Therefore, our results reveal how glutamine carbon and nitrogen are coordinatively metabolized under hypoxia, and provide a comprehensive understanding on glutamine metabolism.
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