ArticleCell metabolism2018
As Extracellular Glutamine Levels Decline, Asparagine Becomes an Essential Amino Acid.
Article in Cell metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 papers, 1 of them a synthesis that pooled it.
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Who cites it
220 citing papers in PubMed, 1 synthesis or guideline pooled it, 333 citations in OpenAlex.
- Global research trends and emerging themes in amino acid deprivation based cancer therapy: a bibliometric and visualization study.Frontiers in immunology · 2026Pooled it
- Anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab for first-line treatment in advanced natural killer T cell lymphoma.Signal transduction and targeted therapy · 2024Trial
- Molecular mechanisms and targeted therapeutic strategies for glycolytic reprogramming in osteosarcoma.Genes & diseases · 2027Review
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- L-asparaginase reversibly suppresses CD40-mediated B cell activation and antigen-presenting function by metabolic restriction.iScience · 2026Article
- Influence of Different Closure Systems on Yeast Metabolism During the Secondary Fermentation of Traditional Method Sparkling Wines.Microorganisms · 2026Article
- Direct pharmacological targeting of asparagine synthetase to overcome resistance to L-asparaginase in ALL therapy.JCI insight · 2026Article
- Cardiac regeneration and repair: the emerging mechanisms and therapeutic approaches.Molecular biomedicine · 2026Review
- Article
- TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis.JCI insight · 2026Article
- Article
- Optimal Combination of Glycine, Asparagine, and Phenylalanine Promotes α-Casein Synthesis and Secretion in MAC-T Cells Through Activation of the PI3K-AKT-mTOR Pathway.Animals : an open access journal from MDPI · 2026Article
- Voluntary running exercise is associated with metabolic shifts linked to adult hippocampal neurogenesis.Scientific reports · 2026Article
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- METTL1-mediated mOncogene · 2026Article
- The lncRNA DAMER selectively guides mNature cell biology · 2026Article
- Article
- The glutaminase activity of ASNS fuels glutamine metabolism in leukemia.Haematologica · 2026Article
- The Glutamine-α-Ketoglutarate Metabolic Axis Controls Vascular Smooth Muscle Cell Function.Cells · 2026Article
- Ribosome-associated quality control of aberrant protein production during amino acid limitation.bioRxiv : the preprint server for biology · 2026Article
160 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
When mammalian cells are deprived of glutamine, exogenous asparagine rescues cell survival and growth. Here we report that this rescue results from use of asparagine in protein synthesis. All mammalian cell lines tested lacked cytosolic asparaginase activity and could not utilize asparagine to produce other amino acids or biosynthetic intermediates. Instead, most glutamine-deprived cell lines are capable of sufficient glutamine synthesis to maintain essential amino acid uptake and production of glutamine-dependent biosynthetic precursors, with the exception of asparagine. While experimental introduction of cytosolic asparaginase could enhance the synthesis of glutamine and increase tricarboxylic acid cycle anaplerosis and the synthesis of nucleotide precursors, cytosolic asparaginase suppressed the growth and survival of cells in glutamine-depleted medium in vitro and severely compromised the in vivo growth of tumor xenografts. These results suggest that the lack of asparaginase activity represents an evolutionary adaptation to allow mammalian cells to survive pathophysiologic variations in extracellular glutamine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.