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Concentrations of PRPP and PRPP synthetase activity did not increase in control cells in medium containing aminopterin unless hypoxanthine was removed from the medium. Exposure of cells to cycloheximide, a protein synthesis inhibitor, prevented the induction of PRPP synthetase and the formation of high PRPP concentrations. Cells from a patient with a mutant HPRT with a high Michaelis constant for PRPP increased PRPP levels and PRPP synthetase activity to a new steady state when they were grown in medium containing aminopterin. Inhibitors of de novo purine synthesis, the presence of hypoxanthine in the medium, and mutant HPRT activity affect the regulation of PRPP levels and PRPP synthetase activity.<\/jats:p>","DOI":"10.1126\/science.201027","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T16:03:07Z","timestamp":1160064187000},"page":"1171-1173","source":"Crossref","is-referenced-by-count":13,"title":["Phosphoribosylpyrophosphate Synthesis in Cultured Human Cells"],"prefix":"10.1126","volume":"198","author":[{"given":"Paul J.","family":"Benke","sequence":"first","affiliation":[{"name":"Mailman Center for Child Development, University of Miami School of Medicine, Miami, Florida 33152"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Dittmar","sequence":"additional","affiliation":[{"name":"Mailman Center for Child Development, University of Miami School of Medicine, Miami, Florida 33152"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","first-page":"132","volume":"43","year":"1976","unstructured":"BECKER, M.A., BIOCHIM BIOPHYS ACTA 43: 132 (1976).","journal-title":"BIOCHIM BIOPHYS ACTA"},{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1172\/JCI108282","volume":"57","year":"1976","unstructured":"BECKER, M.A., PATTERNS OF PHOSPHORIBOSYLPYROPHOSPHATE AND RIBOSE-5-PHOSPHATE CONCENTRATION AND GENERATION IN FIBROBLASTS FROM PATIENTS WITH GOUT AND PURINE OVERPRODUCTION, JOURNAL OF CLINICAL INVESTIGATION 57: 308 (1976).","journal-title":"JOURNAL OF CLINICAL INVESTIGATION"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/0002-9343(72)90046-0","volume":"52","year":"1972","unstructured":"BENKE, P.J., AZAGUANINE-RESISTANCE AS A MANIFESTATION OF A NEW FORM OF METABOLIC OVERPRODUCTION OF URIC-ACID, AMERICAN JOURNAL OF MEDICINE 52: 547 (1972).","journal-title":"AMERICAN JOURNAL OF MEDICINE"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/0006-2944(73)90035-5","volume":"8","year":"1973","unstructured":"BENKE, P.J., TRANSPORT OF HYPOXANTHINE IN FIBROBLASTS WITH NORMAL AND MUTANT HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE, BIOCHEMICAL MEDICINE 8: 309 (1973).","journal-title":"BIOCHEMICAL MEDICINE"},{"key":"e_1_2_1_5_1","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1172\/JCI107409","volume":"52","year":"1973","unstructured":"BENKE, P.J., HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE VARIANT ASSOCIATED WITH ACCELERATED PURINE SYNTHESIS, JOURNAL OF CLINICAL INVESTIGATION 52: 2234 (1973).","journal-title":"JOURNAL OF CLINICAL INVESTIGATION"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1172\/JCI108471","volume":"58","year":"1976","unstructured":"BROSH, S, DENOVO SYNTHESIS OF PURINE NUCLEOTIDES IN HUMAN PERIPHERAL-BLOOD LEUKOCYTES - EXCESSIVE ACTIVITY OF PATHWAY IN HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE DEFICIENCY, JOURNAL OF CLINICAL INVESTIGATION 58: 289 (1976).","journal-title":"JOURNAL OF CLINICAL INVESTIGATION"},{"key":"e_1_2_1_7_1","first-page":"1","volume":"9","year":"1976","unstructured":"DOSSETOR, J.B., CLIN BIOCHEM 9: 1 (1976).","journal-title":"CLIN BIOCHEM"},{"key":"e_1_2_1_8_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/jcp.1040880309","volume":"88","year":"1976","unstructured":"GRAF, L.H., INCREASED PRPP SYNTHETASE-ACTIVITY IN CULTURED RAT HEPATOMA-CELLS CONTAINING MUTATIONS IN HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE GENE, JOURNAL OF CELLULAR PHYSIOLOGY 88: 331 (1976).","journal-title":"JOURNAL OF CELLULAR PHYSIOLOGY"},{"key":"e_1_2_1_9_1","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1016\/S0021-9258(18)97329-1","volume":"240","year":"1965","unstructured":"HENDERSON, J.F., SYNTHESOS OF 5-PHOSPHORIBOSYL 1-PYROPHOSPHATE FROM GLUCOSE IN EHRLICH ASCITES TUMOR CELLS IN VITRO, JOURNAL OF BIOLOGICAL CHEMISTRY 240: 2349 (1965).","journal-title":"JOURNAL OF BIOLOGICAL CHEMISTRY"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)93405-8"},{"key":"e_1_2_1_11_1","first-page":"62","year":"1972","unstructured":"Henderson, J. 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