Skip to main content

Use of Metabolic Control Analysis to Design a New Strategy for Cancer Therapy

  • Chapter
Technological and Medical Implications of Metabolic Control Analysis

Abstract

The synthesis of nucleic acids is much more active in cancer than in normal cells, and is a process of the utmost importance in tumour proliferation. At present, conventional cancer treatment is directed only at the inhibition of synthesis of the purine and pyrimidine bases. Antimetabolites and alkylating agents are cancer chemotherapeutic agents that inhibit nucleic acid synthesis by preventing the synthesis of substrates for only half of the nucleic acid molecule, namely the purine and pyrimidine bases. It has been well known since the 193os that glucose metabolism is increased in malignant tissues (Warburg, 1930, 1956). The increase in glucose metabolism is accompanied not only by an increase of lactate production but also by an increase in pentose production for RNA and DNA synthesis (Eigenbrodt et al., 1985).However, the importance of the pentose phosphate pathway in tumours has been overlooked.

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

Access this chapter

eBook
USD 16.99
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
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover 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

  • Basu, T. K. & Dickerson, J. W. (1976) The thiamin status of early cancer patients with par-ticular reference to those with breast and bronchial carcinomasOncology33, 250–252

    Article  PubMed  CAS  Google Scholar 

  • Ben-Yoseph, O., Camp, D. M., Robinson, T. E. & Ross, B. D. (1995) Dynamic measurement of cerebral pentose phosphate pathway activity invivousing [1,6–13C26,6–2H2]glucose and microdialysisJ. Neurochem.64, 1336–1342

    Article  PubMed  CAS  Google Scholar 

  • Boros, L. G., Puigjaner, J., Cascante, M., Lee, W. N. P.et al.(1997) Oxythiamine and dehydroepiandrosterone inhibit the nonoxidative synthesis of ribose and tumor cell proliferationCancer Res.57, 4242-4248

    PubMed  CAS  Google Scholar 

  • Boros, L. G., Brandes, J. L., Lee, W. N., Cascante, M. etal.(1998) Thiamine supplementation to cancer patients: a double edged swordAnticancer Res.18, 595–602

    PubMed  CAS  Google Scholar 

  • Cascante, M., Canela, E. I., Franco, R. (1990) Control analysis of systems having two steps catalysed by the same protein molecule in unbranched chainsEur. J. Biochem. 192369–371

    Article  PubMed  CAS  Google Scholar 

  • Champe, P. C. & Harvey, R. A. (1994) Hexose monophosphate pathway. Oxidative reactions and nonoxidative reactions, pp. 110–113 in Biochemistry, 2nd edn., Lippincott, Philadelphia

    Google Scholar 

  • Cornish-Bowden, A. (1995) Kinetics of multi-enzyme systems, pp. 121–136 in Biotechnology (ed. Rehm, H.-J. & Reed, G.), 2nd edn., vol. 9, Verlag Chemie, Weinheim

    Chapter  Google Scholar 

  • Eigenbrodt, E., Fister, P. & Reinacher, M. (1985) New perspectives on carbohydrate metabolism in tumor cells, pp. 141–179 inRegulation of Carbohydrate Metabolism(ed. Beitner, R.), vol. 2, CRC Press, Boca Raton, Florida

    Google Scholar 

  • Fell, D. (1997)Understanding the Control of MetabolismPortland Press, London

    Google Scholar 

  • Georgiannos, S. N., Weston, P. M. & Goode, A. W. (1993) Micronutrients in gastrointestinal cancerBr. J. Cancer68, 1195–1198

    Article  PubMed  CAS  Google Scholar 

  • Groen, A. K. & Westerhoff, H. V. ((1990) Modern control theories: a consumers’ test, pp. l01–118 inControl of Metabolic Processes(ed. Cornish-Bowden, A. & Cárdenas, M. L.), Plenum Press, New York

    Google Scholar 

  • Heinrich, R. & Rapoport, T. A. (1974) A linear steady-state treatment of enzymatic chains: general properties, control and effector strengthEur. J. Biochem. 4289–95

    Article  PubMed  CAS  Google Scholar 

  • Henquin, N., Havivi, J., Reshef, A., Barak, F. & Horn, Y. (1989) Nutritional monitoring and counselling for cancer patients during chemotherapyOncology46, 173–177

    Article  PubMed  CAS  Google Scholar 

  • Hiatt, H. H. (1957) Studies of ribose metabolism. I. The pathway of nucleic ribose synthesis in human carcinoma cell in tissue cultureJ. Clin. Invest.36, 1408–1415

    Article  PubMed  CAS  Google Scholar 

  • Horecker, B. L. & Mehler, A. H. (1955) Carbohydrate metabolismAnnu. Rev. Biochem. 24207–274

    Article  PubMed  CAS  Google Scholar 

  • Kacser, H. & Burns, J. A. (1973) The control of fluxSymp. Soc. Exp. Biol.27, 65–104

    PubMed  CAS  Google Scholar 

  • Katz, J. & Rognstad, R. (1967) The labeling of pentose phosphate from glucose-4C and estimation of the rates of transaldolase, transketolase, the contribution of the pentose cycle, and ribose phosphate synthesisBiochemistry6, 2227–2247

    Article  PubMed  CAS  Google Scholar 

  • Krebs, H. A. (1957) Control of metabolic processesEndeavour16,125–132

    CAS  Google Scholar 

  • Lee, W. N., Boros, L. G., Puigjaner, J., Bassilian, S.et al.(1998) Mass isotopomer study of the nonoxidative pathways of the pentose cycle with [I,2–13C2]glucoseAm. J. Physiol.274, E843–E851

    PubMed  CAS  Google Scholar 

  • Macallan, D. C., Fullerton, C. A., Neese, R. A., Haddock, K.et al.(1998) Measurement of cell proliferation by labeling of DNA with stable isotope-labeled glucose: studies invitroin animals, and in humansProc. Natl. Acad. Sci. USA5, 708–713

    Article  Google Scholar 

  • Mahan, K. L. & Arlin, M. (1992) Thiamine (vitamin BI), pp. 85–87 inFood Nutrition and Diet Therapy8th edn. (ed. Mahan, K. L. & Arlin, M.), Saunders, Philadelphia

    Google Scholar 

  • Ross, B. D., Kingsley, P. B. & Ben-Yoseph, O. (1994) Measurement of pentose phosphate pathway activity in a single incubation with [1,6–13C26,6–2H2]glucoseBiochem. J.302, 31–38

    PubMed  CAS  Google Scholar 

  • Sabaté, L., Franco, R., Canela, E. I., Centelles, J. J. & Cascante, M. (1995) A model of the pentose phosphate pathway in rat liver cellsMol. Cell. Biochem.142, 9–17

    Article  PubMed  Google Scholar 

  • Savageau, M. A. (1969a) Biochemical systems analysis. I. Some mathematical properties of the rate law for the component enzymatic reactionsJ. Theor. Biol.25, 365–369

    Article  CAS  Google Scholar 

  • Savageau, M. A. (1969b) Biochemical systems analysis. n. The steady-state solutions for an n-pool system using a power law approximationJ. Theor. Biol.25, 370-379

    Google Scholar 

  • Seear, M., Lockitch, G., Jacobson, B., Quigley, G. & MacNab, A. (1992) Thiamine, riboflavin, and pyridoxine deficiencies in a population of critically ill childrenJ. Pediatrics121, 533–538

    Article  CAS  Google Scholar 

  • Small, J. R. & Kacser, H. (1993) Responses of metabolic systems to large changes in enzyme activities and effectors. 1. The linear treatment of unbranched chainsEur. J. Biochem.213, 613–624

    Article  PubMed  CAS  Google Scholar 

  • Stephanopoulos, G. & Vallino, J. J. (1991) Network rigidity and metabolic engineering in metabolic overproductionScience252, 1675–1681

    Article  PubMed  CAS  Google Scholar 

  • Voit, E. O. (1991)Canonical Nonlineal Modeling: S-System Approach to Understanding ComplexityVan Nostrand Reinhold, New York

    Google Scholar 

  • Warburg, O. (1930)The Metabolism of TumoursConstable, London

    Google Scholar 

  • Warburg, O. (1956) On the origin of cancer cellsScience123, 309–314

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Cascante, M. et al. (2000). Use of Metabolic Control Analysis to Design a New Strategy for Cancer Therapy. In: Cornish-Bowden, A., Cárdenas, M.L. (eds) Technological and Medical Implications of Metabolic Control Analysis. NATO Science Series, vol 74. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4072-0_19

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-4072-0_19

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-0-7923-6189-3

  • Online ISBN: 978-94-011-4072-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics