Abstract
Very low erythrocyte hypoxanthine phosphoribosyl transferase activity was found in a 6-month-old child with microcephaly, hyperuricemia, and retardation of central nervous development, who subsequently developed self-mutilation. Fibroblast cell extracts from this patient showed less than 6% of normal activity of HPRT. Major metabolic products of adenine-8-C14 by extracts from both the patient and normal subjects were identified by high-voltage electrophoresis and paper chromatography as adenosine 5′-monophosphate, adenosine, and inosine. Inosine was the principal product of the fibroblast cell extracts from the first biopsy of the patient, whereas the normal fibroblast cell extracts produced predominantly adenosine. These results suggest that interconversion of the purine nucleotides plays a significant role in metabolism of these fibroblast cell extracts.
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References
Balis, M. E. (1968). Aspects of purine metabolism. Fed. Proc. 271067.
Emmerson, B. T., and Wyngaarden, J. B. (1969). Purine metabolism in heterozygous carriers of hypoxanthine-guanine phosphoribosyltransferase deficiency. Science 1661533.
Fujimoto, W. Y., and Seegmiller, J. E. (1970). Hypoxanthine-guanine phosphoribosyltransferase deficiency: Activity in normal, mutant, and heterozygote-cultured human skin fibroblasts. Proc. Natl. Acad. Sci. 65577.
Fujimoto, W. Y., Greene, M. L., and Seegmiller, J. E., Jr. (1968). X-linked uric aciduria with neurological disease and self-mutilation: Diagnostic test for the enzyme defect. J. Pediat. 73920.
Itiaba, K., Banfalvi, M., and Crawhall, J. C. (1972). Variations in purine phosphoribosyl transferase enzymes during growth of fibroblast cell cultures. Biochem. Med. (in press).
Kelley, W. N., Rosenbloom, F. M., Henderson, J. F., and Seegmiller, J. E. (1967). A specific enzyme defect in gout associated with overproduction of uric acid. Proc. Natl. Acad. Sci. 571735.
Kelley, W. N., Greene, M. L., Rosenbloom, F. M., Henderson, J. F., and Seegmiller, J. E. (1969). Hypoxanthine-guanine phosphoribosyltransferase deficiency in gout. Ann. Int. Med. 70155.
Lesch, M., and Nyhan, W. L. (1964). A familial disorder of uric acid metabolism and central nervous system function. Am. J. Med. 36561.
Liddle, L., Seegmiller, J. E., and Laster, L. (1959). The enzymatic spectrophotometric method for determination of uric acid. J. Lab. Clin. Med. 54903.
Lowry, O. H., Rosenbrough, N. J., Farr, A. L., and Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193265.
Murray, A. W., and Friedrichs, B. (1969). Inhibition of 5′-nucleotidase from Ehrlich ascites tumour cells by nucleoside triphosphates. Biochem. J. 11183.
Parker, R., Snedden, W., and Watts, R. W. E. (1969). The mass-spectrometric identification of hypoxanthine and xanthine (“oxpurines”) in skeletal muscle from two patients with congenital xanthine oxidase deficiency (xanthinuria). Biochem. J. 115103.
Rubin, C. S., Balis, M. E., Pionelli, S., Berman, P. H., and Dancis, J. (1969). Elevated AMP pyrophosphorylase activity in congenital IMP pyrophosphorylase deficiency (Lesch-Nyhan disease). J. Lab. Clin. Med. 74732.
Seegmiller, J. E., Rosenbloom, F. M., and Kelley, W. N. (1967). Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science 1551682.
Shiio, I., and Ishii, K. (1971). Genetically altered repression pattern of purine nucleotide synthesizing enzymes and inosine production in 8-azaguanine resistant mutants. J. Biochem. 69339.
Sorensen, L. B. (1970). Mechanism of excessive purine biosynthesis in hypoxanthineguanine phosphoribosyltransferase deficiency. J. Clin. Invest. 49968.
Thompson, R. Y. (1960). Purines and pyrimidines and their derivatives. In Smith, I. (ed.), Chromatographic and Electrophoretic Techniques, Vol. 1, Interscience, New York, p. 236.
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This project received support from the M.R.C. grant MA-3331 and the Canadian Arthritis and Rheumatism Society.
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Itiaba, K., Banfalvi, M. & Crawhall, J.C. Metabolism of purines in cultured normal and HPRT-deficient human fibroblasts. Biochem Genet 8, 149–156 (1973). https://doi.org/10.1007/BF00485542
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DOI: https://doi.org/10.1007/BF00485542