Summary
In order to study the biochemical basis of a complete deficiency of adenine phosphoribosyl transferase (APRT) the enzyme was purified to homogeneity, its properties were characterized, and antibodies raised. The enzyme is indirectly involved in adenine uptake. Apparently, by forming AMP the internal concentration of adenine is kept low allowing its diffusion.
The same APRT is present in various tissues as was revealed by antibody inactivations employing anti-erythrocyte APRT as well as by direct enzyme assays in cells from the APRT deficient patient. In vitro cultured fibroblasts derived from this patient had less than 0.02% enzyme activity. No cross-reacting material was found in erythrocytes obtained from an APRT deficient child.
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References
van Acker KJ, Simmonds HA, Potter C, Cameron JS (1977) Complete deficiency of adenine phosphoribosyltransferase: Report of a family. N Engl J Med 297:127–132
Alford BL, Barnes EM (1976) Hypoxanthine transport by cultured Chinese hamster lung fibroblasts. J Biol Chem 251:4823–4827
Barratt TM, Simmonds HA, Cameron JS, Potter CF, Rose GA, Arkell DG, Williams DI (1979) Complete deficiency of adenine phosphoribosyltransferase: A third case presenting as renal stones in a young child. Arch Dis Child 54:25–31
Böyum A (1968) Separation of leucocytes from blood and bone marrow. Scand J Clin Lab Invest 21 [Suppl 97]:1–109
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Anal Biochem 72:248–254
de Bruyn CHMM, Oei TL (1977) Incorporation of purine bases by intact red blood cells. In: Müller MM, Kaiser E, Seegmiller JE (eds) Purine metabolism in man, vol II. Plenum, New York, pp 139–150
Cartier PH (1980) Adenine uptake by isolated rat thymocytes. J Biol Chem 255:4574–4582
Debray H, Cartier P, Temstet A, Cendron J (1976) Child's urinary lithiasis revealing a complete deficit in adenine phosphoribosyl transferase. Pediatr Res 10:762–766
Fox IH, Meade JC, Kelley WN (1973) Adenine phosphoribosyltransferase deficiency in man: Report of a second family. Am J Med 55: 614–620
Freese E, Lopez JM, Freese EB (1979) Initiation of bacterial and yeast sporulation by partial deprivation of guanine nucleotides. In: Koch G, Richter G (eds) Regulation of macromolecular synthesis by low molecular weight mediators. Academic Press, New York, pp 127–143
Giblett ER, Anderson JE, Cohen F, Pollara B, Meuwissen HJ (1972) Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet 1:1067–1069
Giblett ER, Amman AJ, Ware DW, Sandman R, Diamond LK (1975) Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity. Lancet 1:1010–1013
Greene ML, Boyle JA, Seegmiller JE (1970) Substrate stabilizationL Genetically controlled reciprocal relationship of two human enzymes. Science 167:887–889
Grummt F, Speckbacher M (1975) GTP degradation to guanine catalyzed by ribosomal subunits and microsomal-wash factors. Eur J Biochem 57:579–585
Hjelm H (1974) Protein A from Staphylococcus aureus: purification, structural studies and applications of its interaction with immunoglobulin B. Acta Universitatis Upsaliensis 213
Hochstadt-Ozer J (1972) The regulation of purine utilization in bacteria: IV. Roles of membrane localized and pericytoplasmic enzymes in the mechanism of purine nucleoside transport across isolated Escherichia coli membranes. J Biol Chem 247:2419–2426
Holden JA, Meredith GS, Kelley WN (1979) Human adenine phosphoribosyltransferase: affinity purification, subunit structure, amino acid composition, and peptide mapping. J Biol Chem 254:6951–6955
Hughes SH, Wahl GM, Capecchi MR (1975) Purification and characterization of mouse hypoxanthine-guanine phosphoribosyltransferase. J Biol Chem 250:120–126
Lesch M, Nyhan WL (1964) A familial disorder of uric acid metabolism and central nervous system function. Am J Med 36:561–570
Müller MM, Kraupp M, de Bruyn CHMM (1979) Purine base transport in normal and mutant erythrocytes. Hum Hered 29:118–123
Ponta H, Pon CL, Herrlich P, Gualerzi C, Hisch-Kauffmann M, Pfennig-Yeh M, Rahmsdorf HJ (1975) The sex-factor dependent exclusion of colivirus T7. Eur J Biochem 59:261–270
Schabel F, Doppler W, Hisch-Kauffmann M, Glatzl J, Schweiger M, Berger H, Heinz-Erian P (1980) Hereditary deficiency of adenine phosphoribosyl transferase. Paediatr Paedol 15:233–238
Schweiger M, Wagner EF (1979) Nucleosidetriphosphate mediated discrimination of gene expression in T1-infected E. coli. In: Koch G, Richter G (eds) Regulation of macromolecular synthesis by low molecular weight mediators. Academic Press, New York, pp 249–262
Thomas CB, Arnold WJ, Kelley WN (1973) Human adenine phosphoribosyltransferase: purification, subunit structure, and substrate specificity. J Biol Chem 248:2529–2535
Tischfield JA, Ruddle FH (1974) Assignment of the gene for adenine phosphoribosyltransferase to human chromosome 16 by mouse-human somatic cell hybridization. Proc Natl Acad Sci USA 71: 45–49
Wagner EF, Schweiger M (1980) Development of Escherichia coli virus T1: ATP-mediated discrimination of gene expression. J Biol Chem 255:540–542
Watts RWE, Engelman K, Klinenberg JR, Seegmiller JE, Sjoerdsma A (1964) The enzyme defect in xanthinuria. Biochem J 90:4P
Zylka JM, Plagemann PGW (1975) Purine and pyrimidine transport by cultured Novikoff cells: specificities and mechanism of transport and relationship to phosphoribosylation. J Biol Chem 250:5756–5757
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Doppler, W., Hirsch-Kauffmann, M., Schabel, F. et al. Characterization of the biochemical basis of a complete deficiency of the adenine phosphoribosyl transferase (APRT). Hum Genet 57, 404–410 (1981). https://doi.org/10.1007/BF00281694
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DOI: https://doi.org/10.1007/BF00281694