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Flux Control Coefficients of Glycinamide Ribonucleotide Transformylase for de novo Purine Biosynthesis

  • Gary K. Smith
  • Richard G. Knowles
  • Christopher I. Pogson
  • Mark Salter
  • M. Hanlon
  • R. Mullin
Chapter
Part of the NATO ASI Series book series (NSSA, volume 190)

Abstract

The Pathway of de novo purine synthesis in mammals is initiated from phosphoribosylpyrophosphate and incorporates carbon and nitrogen from glutamine, glycine and the onecarbon pool to form initially IMP, from which the other purines can be synthesized. This pathway has been considered to be largely regulated by purines at the first enzyme, phosphoribosylpyrophosphate amidotransferase. In order for this enzyme to be an effective site of feedback regulation it must have a substantial flux control coefficient compared to the other enzymes in the de novo pathway. This feedback inhibitory mechanism results in significant control residing outside the purine de novo pathway, in purine utilization (positive control) and the alternative pathway of purine synthesis, purine salvage (negative control). As part of a continuing anti-tumour effort we are investigating specific steps in the de novo purine synthesis as targets for inhibition in cancer chemotherapy.

Keywords

Control Coefficient Effective Site Purine Synthesis Purine Biosynthesis High Intracellular Concentration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Groen, A. K., Van der Meer, R., Westerhoff, H. V., Wanders, R. J. A., Akerboom, T. P. M. & Tager, J. M. (1982) in Metabolic Compartmentation (Sies, H., ed.) pp 9–37, Academic Press, LondonGoogle Scholar
  2. Kacser, H. & Burns, J. A. (1973) Symp. Soc. Exp. Biol. 27, 65–104PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Gary K. Smith
    • 1
  • Richard G. Knowles
    • 2
  • Christopher I. Pogson
    • 2
  • Mark Salter
    • 2
  • M. Hanlon
    • 1
  • R. Mullin
    • 1
  1. 1.Department of Medicinal ChemistryBurroughs Wellcome CompanyResearch Triangle ParkUSA
  2. 2.Department of Biochemical SciencesThe Wellcome Research LaboratoriesBeckenham, KentUK

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