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.
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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
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
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
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
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
Champe, P. C. & Harvey, R. A. (1994) Hexose monophosphate pathway. Oxidative reactions and nonoxidative reactions, pp. 110–113 in Biochemistry, 2nd edn., Lippincott, Philadelphia
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
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
Fell, D. (1997)Understanding the Control of MetabolismPortland Press, London
Georgiannos, S. N., Weston, P. M. & Goode, A. W. (1993) Micronutrients in gastrointestinal cancerBr. J. Cancer68, 1195–1198
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
Heinrich, R. & Rapoport, T. A. (1974) A linear steady-state treatment of enzymatic chains: general properties, control and effector strengthEur. J. Biochem. 4289–95
Henquin, N., Havivi, J., Reshef, A., Barak, F. & Horn, Y. (1989) Nutritional monitoring and counselling for cancer patients during chemotherapyOncology46, 173–177
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
Horecker, B. L. & Mehler, A. H. (1955) Carbohydrate metabolismAnnu. Rev. Biochem. 24207–274
Kacser, H. & Burns, J. A. (1973) The control of fluxSymp. Soc. Exp. Biol.27, 65–104
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
Krebs, H. A. (1957) Control of metabolic processesEndeavour16,125–132
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
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
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
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
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
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
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
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
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
Stephanopoulos, G. & Vallino, J. J. (1991) Network rigidity and metabolic engineering in metabolic overproductionScience252, 1675–1681
Voit, E. O. (1991)Canonical Nonlineal Modeling: S-System Approach to Understanding ComplexityVan Nostrand Reinhold, New York
Warburg, O. (1930)The Metabolism of TumoursConstable, London
Warburg, O. (1956) On the origin of cancer cellsScience123, 309–314
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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
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DOI: https://doi.org/10.1007/978-94-011-4072-0_19
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