The control of cell proliferation by preformed purines: a genetic study. II. Pleiotropic manifestations and mechanism of a control exerted by adenylic purines on PRPP synthesis.
When plated in medium containing 0.5 microgram/ml coformycin and adenosine (or adenine) fibroblasts were killed, even if pyrimidines were supplied. Measurements of N-formylglycine amide ribonucleotide synthesis showed that lethality is a manifestation of purine starvation. In the case of adenosine kinase deficient cells, growth was restored by hypoxanthine. The adenylic derivatives block only purine biosynthesis, presumably by inhibition of PRPP-amidotransferase. In this same medium, wild-type cells exhibited symptoms of PRPP deprivation: purine and pyrimidine syntheses were both shut off and HGPRT was simultaneously inactivated. The pleiotropic control by adenosine was abolished in adenosine-resistant mutants that behaved as PRPP "over-producers." These mutations conferred partial resistance to various toxic purine and pyrimidine analogs and preserved HGPRT activity in adenosine-containing medium.  This permits selection against these mutants. Evidence suggesting that adenosine kinase products may fulfill a specific function in the regulation of PRPP synthesis is discussed.
D000225:Adenine / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology*; D000248:Adenosine Kinase / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology; D002460:Cell Line; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D009154:Mutation; D010428:Pentosephosphates / Q000096:biosynthesis*; D010754:Phosphoribosyl Pyrophosphate / Q000096:biosynthesis*; D012263:Ribonucleosides / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001381:Azepines; D010428:Pentosephosphates; D012263:Ribonucleosides; D010754:Phosphoribosyl Pyrophosphate; D007041:Hypoxanthine Phosphoribosyltransferase; D000248:Adenosine Kinase; D000225:Adenine; D000241:Adenosine