title: Increased inhibition of HGPRT by IMP and GMP and higher levels of PRPP in an 8-azaguanine - hat resistant mutant of Chinese hamster cells.
abstract: In this paper an 8-azaguanine resistant mutant of Chinese hamster cells able to grow in HAT medium is analyzed. Kinetic analysis of hypoxanthine-guanine-phosphoribosyl-transferase show that the enzyme of the mutant has an altered affinity for both phosphoribosyl-pyrophosphate and the inhibitors IMP and GMP. Furthermore we show that mutant cells exposed to inhibitors of de novo purine synthesis have increased levels of phosphoribosyl-pyrophosphate probably due to decreased utilization by the de novo pathway. These results explain the ability of the mutant to grow both in 8-azaguanine and HAT medium.
mesh_terms: D000818:Animals; D001375:Azaguanine / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D003470:Culture Media; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006157:Guanosine Monophosphate / Q000494:pharmacology*; D019271:Hypoxanthine; D007041:Hypoxanthine Phosphoribosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007042:Hypoxanthines / Q000494:pharmacology; D007291:Inosine Monophosphate / Q000494:pharmacology*; D007292:Inosine Nucleotides / Q000494:pharmacology*; D007700:Kinetics; D009154:Mutation; D010428:Pentosephosphates / Q000378:metabolism*; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism*; D012268:Ribose-Phosphate Pyrophosphokinase / Q000378:metabolism
chemical_list: D003470:Culture Media; D006150:Guanine Nucleotides; D007042:Hypoxanthines; D007292:Inosine Nucleotides; D010428:Pentosephosphates; D007291:Inosine Monophosphate; D019271:Hypoxanthine; D010754:Phosphoribosyl Pyrophosphate; D006157:Guanosine Monophosphate; D007041:Hypoxanthine Phosphoribosyltransferase; D012268:Ribose-Phosphate Pyrophosphokinase; D001375:Azaguanine