Human Glutamine Phosphoribosylpyrophosphate (PP-ribose-P) Amidotransferase: Kinetic, Regulation and Configurational Changes

  • E. W. HolmesJr.
  • J. B. Wyngaarden
  • W. N. Kelley
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 41A)


In a large percentage of patients with gout, hyperuricemia is the result of an increase in the rate of purine biosynthesis de novo (Wyngaarden and Kelley, 1972). Consequently, it is important to understand the molecular basis for the regulation of purine biosynthesis in man.


Enzyme Preparation Sucrose Gradient Large Form Small Form Sedimentation Coefficient 
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  1. Caskey, C.T., Ashton, D.M. and Wyngaarden, J.B. 1964. The enzymology of feedback inhibition of glutamine phosphoribosylpyrophosphate amidotransferase by purine ribonucleotides. J. Biol. Chem. 239: 2570–2579.PubMedGoogle Scholar
  2. Fox, I.H., Wyngaarden, J.B. and Kelley, W.N. 1970. Depletion of erythrocyte phosphoribosylpyrophosphate in man: A newly observed effect of allopurinol. New Eng. J. Med. 283: 1177–1182.CrossRefGoogle Scholar
  3. Fox, I.H. and Kelley, W.N. 1971. Phosphoribosylpyrophosphate in man: Biochemical and clinical significance. Ann. Intern. Med. 74: 424–433.PubMedGoogle Scholar
  4. Hartman, S.C. 1963. Phosphoribosylpyrophosphate amidotransferase: Purification and general catalytic properties. J. Biol. Chem. 238: 3024–3035.PubMedGoogle Scholar
  5. Hill, D.L. and Bennett, L.L., Jr. 1969. Purification and properties of 5-phosphoribosylpyrophosphate amidotransferase from adenocarcinoma, 755 cells. Biochem. 8: 122–130.CrossRefGoogle Scholar
  6. Holmes, E.W., McDonald, J.A., McCord, J.M., Wyngaarden, J.B. and Kelley, W.N. 1973. Human glutamine phosphoribosylpyrophosphate amidotransferase: Kinetic and regulatory properties. J. Biol. Chem. 248: 144–150.PubMedGoogle Scholar
  7. Holmes, E.W., Wyngaarden, J.B. and Kelley, W.N. Human glutamine phosphoribosylpyrophosphate amidotransferase: Two molecular forms interconvertible by purine ribonucleotides and phosphoribosylpyrophosphate. J. Biol. Chem. (in press).Google Scholar
  8. Kelley, W.N., Fox, I.H. and Wyngaarden, J.B. 1970. Essential role purine biosynthesis in cultured human cells. I. Effects of orotic acid. Biochim. Biophys. Acta. 215: 512–516.PubMedCrossRefGoogle Scholar
  9. Kelley, W.N., Greene, M.L., Fox, I.H., Rosenbloom, F.M., Levy, R.I. and Seegmiller, J.E. 1970. Effects of orotic acid on purine and lipoprotein metabolism in man. Metabolism. 19: 1025–1035.PubMedCrossRefGoogle Scholar
  10. Momose, H., Nishikawa, H. and Katsujja, N. 1965. Genetic and biochemical studies of 5’ nucleotide formation. II. Repression of enzyme formation in purine nucleotide biosynthesis in Bacillus subtilis and derivation of depressed mutants. J. Gen. Appl. Microbiol. 11: 211–220.CrossRefGoogle Scholar
  11. Nagy, M. 1970. Regulation of the biosynthesis of purine nucleotides in Schizosaccharomyces pombe. I. Properties of the phosphoribosylpyrophosphate glutamine amidotransferase of the wild strain and of a mutant desensitized towards feedback modifers. Biochim. Biophys. Acta. 198: 471–481.PubMedCrossRefGoogle Scholar
  12. Nierlich, D.P. and Magasanik, B. 1965. Regulation of purine ribonucleotide synthesis by end product inhibition: The effect of adenine and guanine ribonucleotides on the 5’-phosphoribosylpyrophosphate amidotransferase in Aerobacter aerogenes. J. Biol. Chem. 240: 358–365.PubMedGoogle Scholar
  13. Reem, G.H. 1972. De novo purine biosynthesis by two pathways in Burkitt lymphoma cells and in human spleen. J. Clin. Invest. 51: 1058–1062.PubMedCrossRefGoogle Scholar
  14. Rosenbloom, F.M., Henderson, J.F., Caldwell, I.C., Kelley, W.N. and Seegmiller, J.E. 1968. Biochemical bases of accelerated purine biosynthesis de novo in human fibroblasts lacking hypoxanthine-guanine phosphoribosyltransferase. J. Biol. Chem. 243: 1166–1173.PubMedGoogle Scholar
  15. Rottman, F. and Guarino, A.J. 1964. The inhibition of phosphoribosylpyrophosphate amidotransferase activity by Cordecepin monophosphate. Biochim. Biophys. Acta. 89: 465–472.PubMedGoogle Scholar
  16. Rowe, P.B. and Wyngaarden, J.B. 1968. Glutamine phosphoribosylpyrophosphate amidotransferase. Purification, substructure aminoacid composition and absorption spectra. J. Biol. Chem. 243: 6373–6383.PubMedGoogle Scholar
  17. Rowe, P.B., Coleman, M.D. and Wyngaarden, J.B. 1970. Glutamine phosphoribosylpyrophosphate amidotransferase. Catalytic and conformational heterogeneity of the pigeon liver enzyme. Biochem. 9: 1498–1505.CrossRefGoogle Scholar
  18. Schulman, J.D., Greene, M.L., Fujimoto, W.Y. and Seegmiller, J.E. 1971. Adenine therapy for the Lesch-Nyhan syndrome. Ped. Res. 5: 77.CrossRefGoogle Scholar
  19. Wood, A.W. and Seegmiller, J.E. 1973. Properties of 5-phosphoribosyl-l-pyrophosphate amidotransferase from human lymphoblasts. J. Biol. Chem. 248: 139–143.Google Scholar
  20. Wyngaarden, J.B. and Ashton, D.M. 1959. The regulation of activity of phosphoribosylpyrophosphate amidotransferase by purine ribonucleotides: A potential feedback control of purine biosynthesis. J. Biol. Chem. 234: 1492–1496.PubMedGoogle Scholar
  21. Wyngaarden, J.B. and Kelley, W.N. 1972. Gout, in The Metabolic Basis of Inherited Diseases. 3rd ed. J. B. Stanbury, J.B. Wyngaarden, and D.S. Fredrickson. (eds.). pp. 889–968. McGraw-Hill Book Co., Inc. New York.Google Scholar

Copyright information

© Plenum Press, New York 1974

Authors and Affiliations

  • E. W. HolmesJr.
  • J. B. Wyngaarden
    • 1
  • W. N. Kelley
    • 1
  1. 1.Duke University Medical CenterDurhamUSA

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