The DOI matches its Crossref record; 129 of the 129 references it cites were found in a registry or an index.
Cancer cell metabolism: the essential role of the nonessential amino acid, glutamine
Open accessAbstract
Biochemistry textbooks and cell culture experiments seem to be telling us two different things about the significance of external glutamine supply for mammalian cell growth and proliferation. Despite the fact that glutamine is a nonessential amino acid that can be synthesized by cells from glucose-derived carbons and amino acid-derived ammonia, most mammalian cells in tissue culture cannot proliferate or even survive in an environment that does not contain millimolar levels of glutamine. Not only are the levels of glutamine in standard tissue culture media at least ten-fold higher than other amino acids, but glutamine is also the most abundant amino acid in the human bloodstream, where it is assiduously maintained at approximately 0.5 mM through a combination of dietary uptake, de novo synthesis, and muscle protein catabolism. The complex metabolic logic of the proliferating cancer cells' appetite for glutamine-which goes far beyond satisfying their protein synthesis requirements-has only recently come into focus. In this review, we examine the diversity of biosynthetic and regulatory uses of glutamine and their role in proliferation, stress resistance, and cellular identity, as well as discuss the mechanisms that cells utilize in order to adapt to glutamine limitation.
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“Glutamine, which is a nonessential amino acid (NEAA) due to the endogenous glutamine biosynthesis pathway, is currently considered essential in cancer cells because transformed cells consume glutamine at a rate exceeding that of glutamine biosynthesis5.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [5]
In the citing paper
“The gamma-nitrogen of glutamine is used in five reactions in de novo nucleotide synthesis, and its bioavailability controls de novo biosynthesis of pyrimidines and purines (Fig. 2)5.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [5]
In the citing paper
“Although glutamine has been considered an NEAA that is synthesized endogenously, most cancer cells cannot proliferate or survive in a medium that does not contain glutamine5.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [5]
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Cites
The emerging hallmarks of cancer metabolism
Pavlova, N. N., & Thompson, C. B. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.006 · Cited by 5,926 · cited 1×
“Thus, levels of certain metabolites are continuously monitored by a cell, directly informing cellular decisions on gene expression, affecting cellular differentiation as a result (Pavlova & Thompson, 2016).”
Self-citationAn Integrated Genomic Analysis of Human Glioblastoma Multiforme
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Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
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Self-citationModulation of oxidative stress as an anticancer strategy
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Regulated Translation Initiation Controls Stress-Induced Gene Expression in Mammalian Cells
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Leone, R. D., Zhao, L., Englert, J. M., Sun, I.-M., Oh, M.-H., Sun, I.-H., Arwood, M. L., Bettencourt, I. A., Patel, C. H., Wen, J., et al. (2019) · Science · doi:10.1126/science.aav2588 · Cited by 1,169
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Glutamine reliance in cell metabolism
Yoo, H. C., Yu, Y. C., Sung, Y., & Han, J. M. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00504-8 · Cited by 1,021
Metadata
- Authors
- Zhang, J., Pavlova, N. N., & Thompson, C. B.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Thompson, Craig B
- Venue
- The EMBO Journal
- Published
- 2017-04-18
- Volume
- 36
- Issue
- 10
- Pages
- 1302-1315
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC5430235
- OpenAlex
- W2606441315
- Cited by
- 651
- References
- 129
- Citations by year
- 2026: 52 · 2025: 85 · 2024: 93 · 2023: 80 · 2022: 83 · 2021: 74 · 2020: 68 · 2019: 64 · 2018: 43 · 2017: 9
- FWCI
- 5.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Terri Brodeur Breast Cancer Foundation
- HHS|National Institutes of Health (P30 CA008748, P01 CA104838)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
- Keywords
- glutamine, cancer metabolism, non-essential amino acids, glutamine synthesis, glutamine limitation, cellular stress resistance, cell proliferation, cell identity, muscle protein degradation, protein synthesis
- MeSH terms
- Animals, Glutamine, Humans, Neoplasms, Cell Proliferation
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