Kinetic Studies of Hypoxanthine-Guanine Phosphoribosyltransferase in Intact Cells

  • Theodore Page
  • Bohdan Bakay
  • William L. Nyhan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 165)


Since the discovery that a deficiency of the enzyme hypoxanthine guanine phosphoribosyl transferase (HPRT) was responsible for the Lesch-Nyhan syndrome (1,2) and other related ailments of greatly differing severity (3-5), enzyme assays using tissue lysates have failed to demonstrate a correlation between the degree of the enzyme deficiency and the severity of the accompanying clinical manifestations (5). Presumably this is because a mutant enzyme molecule may have decreased stability and show less activity after cell lysis than it actually possesses in vivo (4-6). Particularly noteworthy are cases in which individuals with virtually no demonstrable HPRT activity in their erythrocyte lysates show only hyperuricemia, without the behavioral and neurological abnormalities seen in the Lesch-Nyhan syndrome (5). Several investigators have shown that the activities measured in cell lysates may differ considerably from those measured in the intact cell (4,7). Using the incorporation of radiolabeled hypoxanthine into purine compounds as a measure of HPRT activity in the intact cell, it has been possible to show a close correlation between residual enzyme activity and the severity of the clinical symptoms in HPRT deficiency diseases (9). It appears that this more physiological approach is of greater value in assessing in vivo enzyme function. It is possible that cases in which there is a partial deficiency of HPRT with intermediate severity of symptoms may represent HPRT molecules with increased Km’s.


Intact Cell Residual Enzyme Activity Erythrocyte Lysate Lanthanum Chloride Roller Bottle 
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  1. 1.
    Lesch, M., and Nyhan, W. L., 1964, Amer. J. Med., 36:561PubMedCrossRefGoogle Scholar
  2. 2.
    Seegmiller, J. E., Rosenbloom. F. M., and Kelley, W. N., 1967, Science, 155:1682.Google Scholar
  3. 3.
    Kelleyy, W. N., Rosenbloom, F. M., Henderson, J. F., and Seegmiller, J. E., 1967, Proc. Nat. Acad. Sci., 57:1735.CrossRefGoogle Scholar
  4. 4.
    Bakay, B., Nissine, E., Sweetman, L., Franke, U., and Nyhan, W. L., 1979, Pediatr. Res., 13:1365.PubMedCrossRefGoogle Scholar
  5. 5.
    Emmerson, B. T., and Thompson, L., 1973, Q. J. Med., 42:423.PubMedGoogle Scholar
  6. 6.
    Arnold, W. J., Mead, J. C., and Kelley, W. N., 1972, J. Clin. Invest., 51:1805.PubMedCrossRefGoogle Scholar
  7. 7.
    Holland, M. J. C., DiLorenzo, A. M., Danois, J., Balis, M. E., Yu, T.E., and Cox, R. P., 1976, J. Clin. Invest., 57:1600.PubMedCrossRefGoogle Scholar
  8. 8.
    Bakay, B., Nissinen, E., and Sweetman, L., 1978, Anal. Biochem., 86:65.PubMedCrossRefGoogle Scholar
  9. 9.
    Page, T. M., Bakay, B., Nissinen, E., and Nyhan, W. L., 1981, J. Inner. Metab. Dis., 4:203.CrossRefGoogle Scholar
  10. 10.
    Bakay, B., Telfer, M. A., and Nyhan, W. L., 1969, Biochem. Med., 3:230.CrossRefGoogle Scholar
  11. 11.
    Wilkinson, G. N., 1961, Biochem. J., 80:324.PubMedGoogle Scholar
  12. 12.
    Sweetman, L., Hoch, M., Bakay, B., Borden, M., Lesh, P., and Nyhan, W. L., 1978, J. Pediatr., 92:385.PubMedCrossRefGoogle Scholar
  13. 13.
    Henderson, J. F., Brox, L. W., Kelley, W. N., Rosenbloom, F. M., and Seegmiller, J.E., 1968, J. Biol. Chem., 243:2514.PubMedGoogle Scholar
  14. 14.
    Kreinitzky, T. A., and Papaioannou, R., 1969, J. Biol. Chem., 244:1271.Google Scholar
  15. 15.
    Bakay, B., Nyhan, W. L., Fawcett, N., and Kogut, M. D., 1972, Biochem. Genet., 7:73.PubMedCrossRefGoogle Scholar
  16. 16.
    Kelley, W. N., and Wyngaarden, J. B., 1976, in Handbuch der Inneren Medizin 2:603, Springer-Verlag, Berlin.Google Scholar
  17. 17.
    Murphy, E., Holland, M. J. C., and Cox, R. P., 1977, Exp. Cell Res., 108:461.PubMedCrossRefGoogle Scholar
  18. 18.
    Plageman, P. G., and Richey, D. P., 1974, Biochim. Biophys. Acta., 344:263.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Theodore Page
    • 1
  • Bohdan Bakay
    • 1
  • William L. Nyhan
    • 1
  1. 1.Department of PediatricsUniversity of CaliforniaSan Diego La JollaUSA

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