ArticleProceedings of the National Academy of Sciences of the United States of America2020
Quantitative analysis of amino acid metabolism in liver cancer links glutamate excretion to nucleotide synthesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 81 citations in OpenAlex.
- Illuminating spatial dynamics of glutamine metabolism with a sensitive genetically encoded biosensor.RSC chemical biology · 2026Article
- Targeting the nervous system: Mechanistic insights into neuro-tumor communication and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Atomic elementary flux modes explain the steady state flow of metabolites in large-scale flux networks.Cell reports methods · 2026Article
- LATS1/2-CD38 Metabolic Rewiring Links Senescence to Intraplaque Thrombosis.Circulation research · 2026Article
- Hyperglutaminolysis drives senescence and aging through arginine-mTORC1 axis activation.Signal transduction and targeted therapy · 2026Article
- Illuminating spatial dynamics of glutamine metabolism with a sensitive genetically encoded biosensor.bioRxiv : the preprint server for biology · 2026Article
- The ionotropic AMPA receptor contributes to autoimmunity via altered regulatory T cell differentiation.iScience · 2026Article
- The Role of Mitochondrial Dysfunction in Hepatocellular Carcinoma: From Pathogenesis and Drug Resistance to Targeted Therapeutic Strategies.Journal of hepatocellular carcinoma · 2026Review
- From Genome to Function: Metabolism-Wide Models of Lifecycle Stages of Parasites.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Multiomic Analysis Links Neighborhood Disadvantage to Inflammatory Proteins and Tumorigenic Markers in ER+ Breast Cancer Plasma and Tumor Samples.Journal of proteome research · 2025Article
- Amino Acid Hepatotoxicity Biomarkers in Human Hepatic Organoids: Promising Standardization of Drug Toxicity Evaluation.ACS pharmacology & translational science · 2025Article
- Genome-scale modeling identifies dynamic metabolic vulnerabilities during the epithelial to mesenchymal transition.Communications biology · 2024Article
- Advancements in nutritional diagnosis and support strategies during the perioperative period for patients with liver cancer.World journal of gastrointestinal surgery · 2024Review
- Metabolic collaboration between cells in the tumor microenvironment has a negligible effect on tumor growth.Innovation (Cambridge (Mass.)) · 2024Article
- Interpreting protein abundance in Saccharomyces cerevisiae through relational learning.Bioinformatics (Oxford, England) · 2024Article
- Glutamine addiction in tumor cell: oncogene regulation and clinical treatment.Cell communication and signaling : CCS · 2024Review
- Amino Acid and Glucose Fermentation Maintain ATP Content in Mouse and Human Malignant Glioma Cells.ASN neuro · 2024Article
- Brain microvascular endothelial cell metabolism and its ties to barrier function.Vitamins and hormones · 2024Article
- Targeting YAP1 to improve the efficacy of immune checkpoint inhibitors in liver cancer: mechanism and strategy.Frontiers in immunology · 2024Review
- Inferring mitochondrial and cytosolic metabolism by coupling isotope tracing and deconvolution.Nature communications · 2023Article
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many cancer cells consume glutamine at high rates; counterintuitively, they simultaneously excrete glutamate, the first intermediate in glutamine metabolism. Glutamine consumption has been linked to replenishment of tricarboxylic acid cycle (TCA) intermediates and synthesis of adenosine triphosphate (ATP), but the reason for glutamate excretion is unclear. Here, we dynamically profile the uptake and excretion fluxes of a liver cancer cell line (HepG2) and use genome-scale metabolic modeling for in-depth analysis. We find that up to 30% of the glutamine is metabolized in the cytosol, primarily for nucleotide synthesis, producing cytosolic glutamate. We hypothesize that excreting glutamate helps the cell to increase the nucleotide synthesis rate to sustain growth. Indeed, we show experimentally that partial inhibition of glutamate excretion reduces cell growth. Our integrative approach thus links glutamine addiction to glutamate excretion in cancer and points toward potential drug targets.
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