Abstract
Radioautographic examination of the bone marrow of three patients with X-linked congenital hyperuricosuria (Lesch-Nyhan's disease), after incubation with radioactive hypoxanthine, revealed no labeling even in extremely immature blood cells. An adequacy of the cosubstrate, phosphoribosepyrophosphate, in these cells was demonstrated by the appearance of labeling following incubation with tritiated adenine. It is concluded that the enzyme IMP pyrophosphorylase (inosinate: pyrophosphate phosphoribosyltransferase E.C.2.4.2.8) is deficient in young blood cells as well as in peripheral blood elements. The possibility that the enzyme deficiency in the peripheral blood results from the rapid degradation of an unstable enzyme is thereby excluded. Absence of radioactive labeling of terminal cells—erythrocytes, granulocytes, and platelets—is attributed to an insufficiency of the cosubstrate, phosphoribosepyrophosphate.
Similar content being viewed by others
References
Balis, M. E., Krakoff, I. H., Berman, P. H., and Dancis, J. (1967). Urinary metabolites in congenital hyperuricosuria. Science 156 1122.
Berman, P. H., Balis, M. E., and Dancis, J. (1968). Diagnostic test for congenital hyperuricemia with central nervous system dysfunction. J. Lab. Clin. Med. 71 247.
Berman, P. H., Balis, M. E., and Dancis, J. (1969). Congenital hyperuricemia: An inborn error of purine metabolism associated with psychomotor retardation, athetosis and self-mutilation. Arch. Neurol. 20 43.
Dancis, J., Berman, P. H., Jansen, V., and Balis, M. E. (1968). Absence of mosaicism in the lymphocyte in X-linked congenital hyperuricosuria. Life Sci. 7 587.
Hastings, J., Freedman, S., Rendon, O., Cooper, H. L., and Hirschhorn, K. (1961). Culture of human white cells using differential leucocyte separation. Nature 192 1214.
Herschko, A., Razin, A., Shoshani, T., and Mager, J. (1967). Turnover of purine nucleotides in rabbit erythrocytes. II. Studies in vitro. Biochem. Biophys. Acta 149 59.
Joftes, D. L. (1959). Liquid emulsion autoradiography with tritium. Lab. Invest. 8 131.
Kelley, W. N., Rosenbloom, F. M., Henderson, F. J., and Seegmiller, J. E. (1967). Xanthine phosphoribosyltransferase in man: Relationship to hypoxanthine-guanine phosphoribosyltransferase. Biochem. Biophys. Res. Commun. 28 340.
Kornberg, A., Lieberman, I., and Simms, E. S. (1955). Enzymatic synthesis and properties of 5-phosphoribosylpyrophosphate. J. Biol. Chem. 215 389.
Lesch, M., and Nyhan, W. L. (1964). A familial disorder of uric acid metabolism and central nervous system function. Am. J. Med. 36 561.
Piomelli, S., Corash, L. M., Davenport, D. D., Miraglia, J., and Amorosi, E. L. (1968). In vivo lability of glucose-6-phosphate dehydrogenase in GdA− and GdMediterranean deficiency. J. Clin. Invest. 47 940.
Rosenbloom, F. M., Kelley, W. N., Henderson, J. F., and Seegmiller, J. E. (1967). Lyon hypothesis and X-linked disease. Lancet 2 605.
Rubin, C. S., Piomelli, S., and Balis, M. E. (unpublished).
Seegmiller, J. E., Rosenbloom, F. M., and Kelley, W. M. (1967). Enzyme defect associated with a sex-linked neurological disorder and excessive purine synthesis. Science 155 1682.
Sorensen, L. B., and Benke, P. J. (1967). Biochemical evidence for a distinct type of primary gout. Nature 13 1122.
Author information
Authors and Affiliations
Additional information
The studies were done in the Special Clinical Unit of New York University Medical Center. Aided by USPHS CA 08748.
Rights and permissions
About this article
Cite this article
Dancis, J., Jansen, V., Berman, P.H. et al. Inosinate pyrophosphorylase activity in immature blood cells in X-linked congenital hyperuricosuria. Biochem Genet 3, 311–316 (1969). https://doi.org/10.1007/BF00485715
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00485715