Metabolic alterations associated with proliferation of mitogen-activated lymphocytes and of lymphoblastoid cell lines: evaluation of glucose and glutamine metabolism
Abstract
In vitro resting, short-term mitogen stimulated, and proliferating rat thymocytes as well as established human T and B lymphoblastoid cell lines were compared in their capacity to metabolize glucose and glutamine as energy source. Furthermore, the pathways of glutamine metabolism in these cells were studied. Compared with resting thymocytes, glucose metabolism of proliferating thymocytes was 36-fold increased during the incubation; 92% of the amount of glucose utilized was converted into trioses mainly lactate, whereas resting cells metabolized only 38% to trioses. However, the latter oxidized 19% of glucose to CO2, as opposed to 1.1% by the proliferating cells. Rates of glucose uptake and degradation to products by the malignant T lymphoblastoid cell line (Jurkat) were nearly identical with those observed with proliferating rat thymocytes, whereas the benign B lymphoblastoid cell lines (DHg-B-1 and LV-B-1) showed significantly higher rates of glucose metabolism. All three transformed lymphoblastoid cell lines, however, metabolized glucose almost completely to lactate as did the proliferating rat thymocytes. Lymphocytes are able to utilize glutamine with glutamate, aspartate and ammonia being the major end-products. A complete recovery of glutamine carbon in the products was obtained with all cells. Glutamine utilization by incubated proliferating rat thymocytes was 8-fold increased as compared to the resting cells. Again the human T lymphoblastoid cell line showed the same rates of glutamine uptake and conversion into products as did the proliferating rat thymocytes, whereas both B lymphoblastoid cell lines had about 2.5-fold enhanced rates as compared to the T cell line. The results indicate that during lymphocyte proliferation caused by mitogen stimulation as well as by permanent transformation into lymphoblastoid cell lines glucose metabolism is altered not only quantitatively but also qualitatively by changing from partly aerobic to almost complete anaerobic glucose breakdown. Glutamine has been found to be a suitable energy source for lymphocytes. About 75% of the amount of glutamate derived from glutamine entered into the citric acid cycle via the aspartate aminotransferase, and the remaining 25% via the glutamate dehydrogenase reaction. The changes in metabolic rates observed in proliferating as well as in transformed or leukemic lymphocytes appear to be reliable parameters to characterize the state of lymphocyte activation or to evaluate the efficacy of lymphokines.
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Preferential conversion of glucose into lactate has been demonstrated in genetically normal proliferating cells and virus-infected cells.
“preferential conversion of glucose into lactate has been later demonstrated in genetically normal proliferating cells, as well as in cells infected by viruses”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Brand et al., 1986
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- Authors
- Brand, K., Leibold, W., Luppa, P., Schoerner, C., & Schulz, A.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University of Veterinary Medicine Hannover, Foundation (DE)
- ORCID
- Luppa, P.
- Venue
- Immunobiology
- Publisher
- Elsevier BV
- Published
- 1986-10
- Volume
- 173
- Issue
- 1
- Pages
- 23-34
- ISSN
- 0171-2985 (ISSN-L)
- OpenAlex
- W2000628687
- Cited by
- 80
- References
- 18
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 7 · 2013: 3 · 2012: 5
- FWCI
- 0.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Immunobiology (publishedVersion)
- PubMed (publishedVersion)
- 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 › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- lymphocyte proliferation, glucose metabolism, glutamine metabolism, thymocytes, lymphoblastoid cell lines, Jurkat cells, B-lymphoblastoid cell lines, T lymphoblastoid cell lines, mitogen stimulation, lactic acid production, anaerobic glycolysis, glutamate, aspartic acid, glutamate dehydrogenase, aspartate aminotransferase
- MeSH terms
- Animals, B-Lymphocytes, Cell Line, Concanavalin A, Energy Metabolism, Glucose, Glutamine, Humans, Leukemia, Lymphoid, Lymphocyte Activation, Mitogens, T-Lymphocytes, Thymus Gland, Rats
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