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Phosphoribosylpyrophosphate Synthetase Superactivity: Detection, Characterization of Underlying Defects, and Treatment

  • Michael A. Becker
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 165)

Abstract

Phosphoribosylpyrophosphate (PRPP) synthetase catalyzes the synthesis of PRPP, a critical substrate common to the de novo and salvage pathways of purine nucleotide synthesis. The PRPP synthetase reaction involves the transfer of the terminal pyrophosphate group of ATP (as a MgATP complex) to the C-1 carbon of ribose-5-P and is dependent on inorganic phosphate (Pi) and Mg2+ which serve as enzyme activators as well as cofactors. Activity of PRPP synthetase is inhibited by a number of phosphorylated compounds including the reaction products (PRPP) and AMP), purine, pyrimidine, and pyridine nucleotides and 2,3-DPG.1 Human PRPP synthetase is composed of a single polypeptide subunit2 the structural gene for which maps to the long arm of the X-chromasome.3 Under appropriate conditions of enzyme and effector concentration in vitro PRPP synthetase subunits are capable of reversible self-association to aggregates containing 2,4,8,16 and 32 subunits, with only the largest two of these containing significant enzyme activity.4

Keywords

Uric Acid Pyridine Nucleotide Purine Nucleotide Acute Gouty Arthritis Maximal Reaction Velocity 
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. 1.
    Fox, I.H., and Kelley, W.N., J. Biol. Chem. 247:2166 (1972).Google Scholar
  2. 2.
    Becker, M.A., Meyer, L.J., Huisman, W.H., Lazar, C., and Adams, W.B., J. Biol. Chem. 252:3911 (1977).PubMedGoogle Scholar
  3. 3.
    Becker, M.A., Yen, R.C.K., Itkin, P., Goss, S.J., Seegmiller, J.E., and Bakay, B, Science 203:1016 (1979).PubMedCrossRefGoogle Scholar
  4. 4.
    Meyer, L.J. and Becker, M.A., J. Biol. Chem. 252:3919 (1977).PubMedGoogle Scholar
  5. 5.
    Sperling, O., Boer, P. Persky-Brosh, S., Kanarek E., and de Vries A., Rev. Europ. Etud. Clin. Biol. 17:703 (1972).Google Scholar
  6. 6.
    Becker, M.A., Meyer, L.J., and Seegmiller, J.E., Am. J. Med. 55: 232 (1975).CrossRefGoogle Scholar
  7. 7.
    Zoref, E., De Vries, A., and Sperling, O., J. Clin. Invest. 56: 1093 (1975).PubMedCrossRefGoogle Scholar
  8. 8.
    Becker, M.A., J. Clin. Invest. 57:308 (1976).PubMedCrossRefGoogle Scholar
  9. 9.
    Becker, M.A., Raivio, K.O., Bakay, B., Adams, W.B., and Nyhan, W.L., J. Clin. Invest. 65:109 (1980).PubMedCrossRefGoogle Scholar
  10. 10.
    Akaoka, I., Fujimori, S., Kamatani, N., Takeuchi, F., Yano, E., Nishida, Y., Hashimoto, A., and Horiuchi, Y., J. Rheumatol. 8: 563 (1981).PubMedGoogle Scholar
  11. 11.
    Becker, M.A., Losman, M.J., Itkin, P., and Simkin, P.A., J. Lab. Clin. Med. 99:945 (1982).Google Scholar
  12. 12.
    Yen, R.C.K., Adams, W.B., Lazar, C., and Becker, M.A., Proc. Natl. Acad. Sci. USA 75:482 (1978).PubMedCrossRefGoogle Scholar
  13. 13.
    Zoref, E., de Vries, A., and Sperling, O., Adv. Exp. Med. Biol. 76A;287 (1977).PubMedGoogle Scholar
  14. 14.
    Simmonds H.A., Webster, D.R., Wilson, J., Fairbanks, L.D. and Potter, C,F., Adv. Exp. Med. Biol. (this volume).Google Scholar
  15. 15.
    Becker, M.A., Kostel, P.J., and Meyer, L.J., J. Biol. Chem. 250: 6822 (1975).PubMedGoogle Scholar
  16. 16.
    Hershko, A., Razin, A., and Mager, J., Biochim. Biophys. Acta 184:64 (1969).Google Scholar
  17. 17.
    Green, C.D., and Martin, D.W., Jr., Proc. Natl. Acad. Sci, USA 70:3698 (1973).PubMedCrossRefGoogle Scholar
  18. 18.
    Lyon, M.F., Nature 190:372 (1961).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Michael A. Becker
    • 1
  1. 1.Department of MedicineThe University of ChicagoChicagoUSA

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