Glucose is essential for proliferation and the glycolytic enzyme induction that provokes a transition to glycolytic energy production.
Open accessAbstract
A transition from aerobic to anaerobic metabolism occurs as mitogen-activated thymocytes undergo proliferation. Glucose utilization and lactate formation increases 18- and 38-fold, respectively, during proliferation. The absolute amount of 14CO2 production by pyruvate dehydrogenase remains constant, while 14CO2 production by the tricarboxylic acid cycle is reduced during transition from a resting to a proliferating state. Addition of 2,4-dinitrophenol, an agent uncoupling oxidative phosphorylation, and phenacinemethosulfate, an electron acceptor, provide evidence that the reduction of glucose oxidation in proliferating thymocytes is caused neither by limitation of the tricarboxylic acid cycle itself nor by an insufficient supply of ADP. Our data suggest that enhanced cytosolic regeneration of NAD+ by induction of the glycolytic enzymes during proliferation effectively competes with NADH transport and its subsequent oxidation in the mitochondria. Mitogen-stimulated rat thymocytes cultured in a conventional medium containing glucose induce their glycolytic enzymes 8-10-fold in the S phase of the cell cycle and divide within a culture period of 72 h. Replacement of glucose by glutamine, glutamine and ribose, or glutamine and uridine prevents glycolytic enzyme induction and thymocyte proliferation. The effect of glucose on glycolytic enzyme induction cannot be mimicked by 3-O-methylglucose or 2-deoxyglucose. In conclusion, glucose is required for proliferation and the glycolytic enzyme induction that mediates the transition from oxidative to glycolytic energy production during the G1/S transition of rat thymocytes.
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In T lymphocytes, glucose is a critical substrate for ATP production.
“In T lymphocytes, glucose is a critical substrate for adenosine triphosphate (ATP) production (4).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [4]
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- Authors
- Greiner, E. F., Guppy, M., & Brand, K.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- ORCID
- Greiner, E F
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1994-12
- Volume
- 269
- Issue
- 50
- Pages
- 31484-31490
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1548610182
- Cited by
- 307
- References
- 50
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 7 · 2023: 2 · 2022: 8 · 2021: 18 · 2020: 16 · 2019: 13 · 2018: 12 · 2017: 11 · 2016: 18 · 2015: 12 · 2014: 12 · 2013: 23 · 2012: 18
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- glucose, thymocyte proliferation, aerobic glycolysis, anaerobic metabolism, NAD+ regeneration, TCA cycle, pyruvate dehydrogenase, 2,4-dinitrophenol, phenazine methosulfate, glutamine, G1/S transition, energy metabolism
- MeSH terms
- Animals, Cell Division, Concanavalin A, Dinitrophenols, Energy Metabolism, Enzyme Induction, Female, Glucose, Glycolysis, Hexokinase, Interleukin-2, L-Lactate Dehydrogenase, Methylglucosides, Phosphofructokinase-1, Pyruvate Kinase, Sulfones, Thymus Gland, Uridine, Rats, Wistar, 3-O-Methylglucose, Rats, In Vitro Techniques
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