Advertisement

Human Phosphoribosylpyrophosphate Synthetase: Relation of Activity and Quaternary Structure

  • Michael A. Becker
  • Laurence J. Meyer
  • William H. Huisman
  • Cheri S. Lazar
  • William B. Adams
Part of the Advances in Experimental Medicine and Biology book series

Abstract

Evidence from a variety of biochemical, pharmacological and clinical studies indicates that the intracellular concentration of 5-phosphoribosyl 1-pyrophosphate (PP-ribose-P)1 is an important determinant of the rate of purine nucleotide and thus uric acid synthesis (Reviews, references 1,2). PP-Ribose-P formation (Figure 1) from ATP and ribose-5-phosphate is catalyzed by the enzyme PP-ribose-P synthetase in a reaction requiring inorganic phosphate (Pi) and magnesium. Small molecule inhibitors also affect PP-ribose-P synthetase activity and include purine, pyrimidine and pyridine nucleotides as well as 2,3-diphosphoglycerate (2,3-DPG) (3). The significance of regulation of the activity of this enzyme is apparent in several families in whom purine overproduction and clinical gout result from different structural mutations in PP-ribose-P synthetase which lead to excessive enzyme activity and PP-ribose-P generation (4–6).

Keywords

Synthetase Activity Pyridine Nucleotide Sedimentation Coefficient Single Protein Band Sedimentation Equil Ibrium 
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.

Abbreviations

PP-ribose-P

5-phosphoribosyl 1-pyrophosphate

ribose-5-P

ribose-5-phosphate

Pi

inorganic phosphate

2, 3-DPG

2, 3-diphosphoglycerate

SDS

sodium dodecylsulfate

DTT

dithiothreitol

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Fox, I.H. and Kelley, W.N.: Ann. Intern. Med. 74: 424–433 (1971).PubMedGoogle Scholar
  2. 2.
    Becker, M.A. and Seegmiller,: Annu. Rev. Med. 25: 15–28 (1974).PubMedCrossRefGoogle Scholar
  3. 3.
    Fox, I.H. and Kelley, W.N.: J. Biol. Chem. 247: 2126–2131 (1972).PubMedGoogle Scholar
  4. 4.
    Sperling, O., Persky-Brosh, S., Boer, P. and DeVries, A.: Biochem. Med. 7: 389–395 (1973).PubMedCrossRefGoogle Scholar
  5. 5.
    Becker, M.A., Kostel, P.J., Meyer, L.J. and Seegmiller, J.E.: Proc. Natl. Acad. Sci. U.S.A. 70: 2749–2752 (1973).PubMedCrossRefGoogle Scholar
  6. 6.
    Becker, M.A.: J. Clin. Invest. 57: 308–318 (1976).PubMedCrossRefGoogle Scholar
  7. 7.
    Fox, I.H. and Kelley, W.N.: J. Biol. Chem. 246: 5739–5748 (1971).PubMedGoogle Scholar
  8. 8.
    Becker, M.A., Kostel, P.J. and Meyer, L.J.: J. Biol. Chem. 250: 6822–6830 (1975).PubMedGoogle Scholar
  9. 9.
    Neville, D.M., Jr.: J. Biol. Chem. 246: 6328–6334 (1971).PubMedGoogle Scholar
  10. 10.
    Reisfield, R.A. and Small, P.A.: Science 152: 1253–1255 (1966).CrossRefGoogle Scholar
  11. 11.
    Weiner, A.M., Piatt, T., and Weber, K.: J. Biol. Chem. 247: 3242–3251 (1972).Google Scholar
  12. 12.
    Yphantis, D.: Biochemistry 3: 297–317 (1964).PubMedCrossRefGoogle Scholar
  13. 13.
    McEwen, C.R.: Anal. Biochem. 20: 114–149 (1967).PubMedCrossRefGoogle Scholar
  14. 14.
    Ackers, G.K.: J. Biol. Chem. 242: 3237–3238 (1967).Google Scholar
  15. 15.
    Siegel, L.M. and Monty, K.J.: Biochim. Biophys. Acta 112: 346–362 (1966).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Michael A. Becker
    • 1
  • Laurence J. Meyer
    • 1
  • William H. Huisman
    • 1
  • Cheri S. Lazar
    • 1
  • William B. Adams
    • 1
  1. 1.Department of MedicineUniversity of California, San Diego and San Diego Veterans Administration HospitalLa JollaUSA

Personalised recommendations