Skip to main content
SpringerLink
Log in

Glutamine Metabolism by Cultured Mammalian Cells

  • Conference paper
Glutamine Metabolism in Mammalian Tissues

Abstract

Cultured mammalian cells are grown in medium containing carbohydrates, amino acids, salts, vitamins, and growth factors. In the 1950’s Eagle [1] identified the basic composition of tissue culture medium, except for the growth factors which were provided by added serum. Based on this work most culture media contain the essential amino acids required by humans [2] plus glutamine, tyrosine, and cystine. Depletion of any one of these amino acids results in cell death [1]. Eagle et al. [3] observed that the glutamine requirement of cells was 10- to 100-fold greater than for any other amino acid. The increased requirement for glutamine was related only marginally to the chemical instability of this amino acid since the daily spontaneous decomposition at 37° C amounted to only 2%–3% of the glutamine in the medium [4]. Although a portion of the glutamine is used for transamination reactions and direct incorporation into protein, we [4, 5] and other investigators [6–8] have proposed that glutamine is oxidized to CO2 to provide a significant portion of the energy requirement of cultured mammalian cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Eagle H (1959) Amino acid metabolism in mammalian cell cultures. Science 130: 432–437

    Article  PubMed  CAS  Google Scholar 

  2. Rose WC (1938) The nutritive significance of the amino acids. Physiol Rev 18: 109–136

    Google Scholar 

  3. Eagle H, Oyama VI, Levy M, Horton CL, Fleischman R (1956) The growth response of mammalian cells in tissue culture to L-glutamine and L-glutamic acid. J Biol Chem 218: 607–616

    PubMed  CAS  Google Scholar 

  4. Zielke HR, Ozand PT, Tildon JT, Sevdalian DA, Corablath M (1976) Growth of human fibroblasts in the absence of glucose utilization. Proc Natl Acad Sci USA 73: 4110–4114

    Article  PubMed  CAS  Google Scholar 

  5. Zielke HR, Ozand PT, Tildon JT, Sevdalian DA, Cornblath M (1978) Reciprocal regulation of glucose and glutamine utilization by cultured human diploid fibroblasts. J Cell Physiol 95: 41–48

    Article  PubMed  CAS  Google Scholar 

  6. Kovačević Z, Morris HP (1972) The role of glutamine in the oxidative metabolism of malignant cells. Cancer Res 32: 326–333

    PubMed  Google Scholar 

  7. Donnelly M, Scheffler IE (1976) Energy metabolism in respiration-deficient and wild type Chinese hamster fibroblasts in culture. J Cell Physiol 89: 39–52

    Article  PubMed  CAS  Google Scholar 

  8. Reitzer LJ, Wice BM, Kennell D (1979) Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. J Biol Chem 254: 2667–2676

    Google Scholar 

  9. Morell B, Froesch ER (1973) Fibroblasts as an experimental tool in metabolic and hormone studies. Eur J Clin Invest 3: 112–118

    Article  PubMed  CAS  Google Scholar 

  10. Bissell MJ, Hatie C, Rubin H (1972) Patterns of glucose metabolism in normal and virus-transformed chick cells in tissue culture. J Natl Cancer Inst 49: 555–565

    PubMed  CAS  Google Scholar 

  11. Bryant JC, Schilling EL, Earle WR (1958) Massive fluid suspension cultures of certain mammalian tissue cells. Glucose utilization and cell proliferation. J Natl Cancer Inst 21: 349–364

    PubMed  CAS  Google Scholar 

  12. Graff S, Moser H, Kastner O, Graff AM, Tannenbaum M (1965) The significance of glycolysis. J Natl Cancer Inst 34: 511–519

    PubMed  CAS  Google Scholar 

  13. Rheinwald JG, Green H (1974) Growth of cultured mammalian cells on secondary glucose sources. Cell 2: 287–293

    Article  PubMed  CAS  Google Scholar 

  14. Sevdalian DA, Zielke HR (1978) Depletion of cellular glycogen during the early logarithmic growth phase of human fibroblasts. Experientia 34: 384–385

    Article  Google Scholar 

  15. Renner ED, Plagemann PGW, Bernlohr RW (1972) Permeation of glucose by simple and facilitated diffusion by Novikoff rat hepatoma cells in suspension culture and its relationship to glucose metabolism. J Biol Chem 247: 5765–5776

    PubMed  CAS  Google Scholar 

  16. Franchi A, Silvestre P, Pouyssegur J (1981) A genetic approach to the role of energy metabolism in the growth of tumor cells: tumorigenicity of fibroblast mutants deficient either in glycolysis or in respiration. Int J Cancer 27: 819–827

    Article  PubMed  CAS  Google Scholar 

  17. Sumbilla CM, Zielke CL, Reed WD, Ozand PT, Zielke HR (1981) Comparison of the oxidation of glutamine, glucose, ketone bodies and fatty acids by human diploid fibroblasts. Biochim Biophys Acta 657: 301–304

    Article  Google Scholar 

  18. Kvamme E, Svenneby G (1961) The effect of glucose on glutamine utilization by Ehrlich ascites tumor cells. Cancer Res 21: 92–98

    PubMed  CAS  Google Scholar 

  19. Zielke HR, Zielke CL, Ozand PT (1984) Glutamine: a major energy source for cultured mammalian cells. Fed Proc 43: 121–125

    PubMed  CAS  Google Scholar 

  20. Kuchka M, Markus HB, Mellman WJ (1981) Influence of hexose conditions on glutamine oxidation of SV-40-transformed and diploid fibroblast human cell lines. Biochem Med 26: 356–364

    Article  PubMed  CAS  Google Scholar 

  21. Sevdalian DA, Ozand PT, Zielke HR (1980) Increase in glutaminase activity during the growth cycle of cultured human diploid fibroblasts. Enzyme 25: 142–144

    PubMed  CAS  Google Scholar 

  22. Knox WE, Horowitz ML, Friedell GH (1969) The proportionality of glutaminase content to growth rate and morphology of rat neoplasms. Cancer Res 29: 669–680

    PubMed  CAS  Google Scholar 

  23. Zielke CL, Zielke HR, Ozand PT (1982) A radioisotope assay for L-glutaminase: the measurement of tritiated water formation from the reaction of L-2-3H glutamine with the L-glutaminase and glutamate oxalacetate transaminase couple. Anal Biochem 127: 134–142

    Article  PubMed  CAS  Google Scholar 

  24. Zielke HR, Sumbilla CM, Sevdalian DA, Hawkins RL, Ozand PT (1980) Lactate: a major product of glutamine metabolism by human diploid fibroblasts. J Cell Physiol 104: 433–441

    Article  PubMed  CAS  Google Scholar 

  25. Sumbilla CM, Ozand PT, Zielke HR (1981) Activities of enzymes required for the conversion of 4-carbon TCA cycle compounds to 3-carbon glycolytic compounds in human diploid fibroblasts. Enzyme 26: 201–205

    PubMed  CAS  Google Scholar 

  26. Reed WR, Zielke HR, Baab PJ, Ozand PT (1981) Ketone bodies, glucose, and glutamine as lipogenic precursors in human diploid fibroblasts. Lipids 9: 677 - 684

    Article  Google Scholar 

  27. Zielke HR, Sumbilla CM, Ozand PT (1981) Effect of glucose on aspartate and glutamate synthesis by human diploid fibroblasts. J Cell Physiol 107: 251–254

    Article  PubMed  CAS  Google Scholar 

  28. Kovačević Z (1971) The pathway of glutamine and glutamate oxidation in isolated mitochondria from mammalian cells. Biochem J 125: 757–763

    PubMed  Google Scholar 

  29. Schwartz JP, Johnson GS (1976) Metabolic effects of glucose deprivation and of various sugars in normal and transformed fibroblast cell lines. Arch Biochem Biophys 173: 237–245

    Article  PubMed  CAS  Google Scholar 

  30. Meister A (1956) Metabolism of glutamine. Physiol Rev 36: 103–127

    PubMed  CAS  Google Scholar 

  31. Perry TL, Berry K, Diamond S, Mak C (1971) Regional distribution of amino acids in human brain obtained at autopsy. J Neurochem 18: 513–519

    Article  PubMed  CAS  Google Scholar 

  32. Felig P (1975) Amino acid metabolism in man. Annu Rev Biochem 44: 933–955

    Article  PubMed  CAS  Google Scholar 

  33. Windmueller HG, Spaeth AE (1974) Uptake and metabolism of plasma glutamine by the small intestine. J Biol Chem 249: 5070–5079

    PubMed  CAS  Google Scholar 

  34. Rapoport S, Rost J, Schultze M (1971) Glutamine and glutamate as respiratory substrates of rabbit reticulocytes. Eur J Biochem 23: 166–170

    Article  PubMed  CAS  Google Scholar 

  35. Bae I-H, Foote RH (1975) Carbohydrate and amino acid requirements and ammonia production of rabbit follicular oocytes matured in vitro. Exp Cell Res 91: 113–118

    Article  PubMed  CAS  Google Scholar 

  36. Stoner GD, Merchant DJ (1972) Amino acid utilization by L-M strain mouse cells in a chemically defined medium. In Vitro 7: 330–343

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pediatric Research, University of Maryland, 655 W. Baltimore Street, Baltimore, MD, 21201, USA

    P. T. Ozand

Authors
  1. H. R. Zielke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. M. Sumbilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. L. Zielke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. T. Tildon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. T. Ozand
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medizinische Universitätsklinik, Hugstetterstraße 55, 7800, Freiburg, Germany

    Dieter Häussinger

  2. Institut für Physiologische Chemie I, Universität Düsseldorf, Moorenstraβe 5, 4000, Düsseldorf, Germany

    Helmut Sies

Rights and permissions

Reprints and permissions

Copyright information

© 1984 Springer- Verlag Berlin Heidelberg

About this paper

Cite this paper

Zielke, H.R., Sumbilla, C.M., Zielke, C.L., Tildon, J.T., Ozand, P.T. (1984). Glutamine Metabolism by Cultured Mammalian Cells. In: Häussinger, D., Sies, H. (eds) Glutamine Metabolism in Mammalian Tissues. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69754-8_16

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-69754-8_16

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-69756-2

  • Online ISBN: 978-3-642-69754-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation