Glutamine in neoplastic cells: Focus on the expression and roles of glutaminases
Abstract
Glutamine is an important source of energy for neoplastic tissues, and products of its metabolism include, among others, glutamate (Glu) and glutathione (GSH), the two molecules that play a key role in tumor proliferation, invasiveness and resistance to therapy. Glutamine hydrolysis in normal and transforming mammalian tissues alike, is carried out by different isoforms of glutaminases, of which the two major are liver-type glutaminase (LGA) and kidney-type glutaminase (KGA). This brief review summarizes available data on the expression profiles and activities of these isoenzymes in different neoplastic tissues as compared to the tissues of origin, and dwells on recent work demonstrating effects of manipulation of glutaminase expression on tumor growth. A comment is devoted to the emerging evidence that LGA, apart from degrading Gln for metabolic purposes, is involved in gene transcription; its enforced overexpression in glioma cells was found to reduce their proliferation and migration.
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Glutamine metabolism plays a critical role in tumor progression by supporting mitochondrial oxidative phosphorylation, supplying TCA cycle intermediates, glutathione synthesis, NEAA synthesis, and producing NADPH.
“Unsurprisingly, glutamine metabolism plays a critical role in tumor progression since it not only supports mitochondrial oxidative phosphorylation but also supplies metabolic intermediates for the TCA cycle, glutathione synthesis, and NEAA synthesis and simultaneously produces NADPH157–159.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [157]
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Glutamine reliance in cell metabolism
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- Authors
- Szeliga, M., & Obara-Michlewska, M.
- Affiliations
- Mossakowski Medical Research Institute, Polish Academy of Sciences (PL)
- Corresponding author
- Szeliga, Monika
- ORCID
- Szeliga, Monika
- Venue
- Neurochemistry International
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 55
- Issue
- 1-3
- Pages
- 71-75
- ISSN
- 0197-0186 (ISSN-L)
- OpenAlex
- W1965847573
- Cited by
- 76
- References
- 82
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 6 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 6 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 4 · 2014: 3 · 2013: 9 · 2012: 9
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurochemistry International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Keywords
- glutamine metabolism, glutaminase, kidney-type glutaminase, tumor energy metabolism, glutamate, glutathione, tumor cell proliferation, treatment resistance, gene transcription, glioma, tumor growth
- MeSH terms
- Animals, Glutaminase, Glutamine, Humans, Isoenzymes, Neoplasms, Tissue Distribution
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