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Human adenine phosphoribosyltransferase: Characterization from subjects with a deficiency of enzyme activity

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Abstract

Adenine phosphoribosyltransferase (APRT) was characterized with respect to specific activity and immunoreactive protein (CRM) levels in hemolysate from 18 members of an APRT-deficient kindred. In addition, lymphoblastoid cell lines were established from six of these subjects and APRT from these cells was characterized in a similar fashion. Levels of specific activity and CRM in patients homozygous for the deficiency were less than 1% of normal. Heterozygous subjects had higher levels of activity and CRM in lymphoblasts than in erythrocytes and, in all cases, the APRT present was normal in terms of isoelectric point, subunit molecular weight, and heat stability. The higher levels of activity and CRM found in lymphoblasts may be due either to expression of a mutant gene product stabilized in a normal:mutant dimer or to autologous regulation.

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References

  • Barratt, T. M., Simmonds, H. A., Cameron, J. S., Potter, C. F., Rose, G. A., Arkell, D. G., and Williams, D. I. (1979). Complete deficiency of adenine phosphoribosyltransferase. A third case presenting as renal stones in a young child. Arch. Dis. Child 54 25.

    Google Scholar 

  • Debray, H., Carter, P., Temstet, A., and Cendron, J. (1976). Child's urinary lithiasis revealing a complete deficit in adenine phosphoribosyltransferase. Pediat. Res. 10 762.

    Google Scholar 

  • Fox, I. H., Meade, J. C., and Kelley, W. N. (1973). Adenine phosphoribosyltransferase deficiency in man. Report of a second family. Am. J. Med. 55614.

    Google Scholar 

  • Gault, H. M., Simmonds, H. A., Snedden, W., Dow, D., Churchill, D. N., and Penney, H. (1981). Urolithiasis due to 2, 8-dihydroxyadenine in an adult. N. Engl. J. Med. 3051570.

    Google Scholar 

  • Holden, J. A., and Kelley, W. N. (1978). Human hypoxanthine-guanine phosphoribosyltransferase: Evidence for a tetrameric structure. J. Biol. Chem. 2534459.

    Google Scholar 

  • Holden, J. A., Meredith, G. S., and Kelley, W. N. (1979). Human adenine phosphoribosyltransferase: Affinity purification, subunit structure, amino acid composition, and peptide mapping. J. Biol. Chem. 2546951.

    Google Scholar 

  • Kelley, W. N., Levy, R. I., Rosenbloom, F. M., Henderson, J. F., and Seegmiller, J. E. (1968). Adenine phosphoribosyltransferase deficiency: A previously underscribed genetic defect in man. J. Clin. Invest. 472281.

    Google Scholar 

  • Lewis, W. H. P. (1973). Common polymorphism of peptidase A. Electrophoretic variants associated with quantitative variation of red cell levels. Ann. Hum. Genet. Lond. 36267.

    Google Scholar 

  • Lowry, O. H., Rosebrough, N. V., Farr, A. L., and Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193265.

    Google Scholar 

  • Povey, S., Corney, G., Lewis, W. H. P., Robson, E. B., Parrington, J. M., and Harris, H. (1972). The genetics of peptidase C in man. Ann. Hum. Gen. Lond. 35455.

    Google Scholar 

  • Sinka, K. P., Lewis, W. H. P., Corney, G., and Harris, H. (1970). Studies on the quantitative variation of human red cell peptidase A activity. Ann. Hum. Gen. Lond. 34153.

    Google Scholar 

  • Turner, B. M., Fisher, R. A., Garthwaite, E., Whale, R. J. and Harris, H. (1973). An account of two new ICD-S variants not detectable in red blood cells. Ann. Hum. Gen. Lond. 37469.

    Google Scholar 

  • VanAcker, K. J., Simmonds, H. A., Potter, C. F., and Cameron, J. S. (1977). Complete deficiency of adenine phosphoribosyltransferase: Report of a family. N. Engl. J. Med 297127.

    Google Scholar 

  • Wilson, J. M., Daddona, P. E., Simmonds, H. A., VanAcker, K. J., and Kelley, W. N. (1981a). Human adenine phosphoribosyltransferase: Immunochemical quantitation and protein blot analysis of mutant forms of the enzyme. J. Biol. Chem. 2571508.

    Google Scholar 

  • Wilson, J. M., Baugher, B. W., Landa, L., and Kelley, W. N. (1981b). Human hypoxanthine-guanine phosphoribosyltransferase: Purification and characterization of mutant forms of the enzyme. J. Biol. Chem. 25610306.

    Google Scholar 

  • Wilson, J. M., Baugher, B. W., Mattes, P. M., Daddona, P. E., and Kelley, W. N. (1982). Human hypoxanthine-guanine phosphoribosyltransferase: Demonstration of structural variants in lymphoblastoid cells derived from patients with a deficiency of the enzyme. J. Clin. Invest. 69706.

    Google Scholar 

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O'Toole, T.E., Wilson, J.M., Gault, M.H. et al. Human adenine phosphoribosyltransferase: Characterization from subjects with a deficiency of enzyme activity. Biochem Genet 21, 1121–1134 (1983). https://doi.org/10.1007/BF00488464

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  • DOI: https://doi.org/10.1007/BF00488464

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