Alpha-5-phosphoribosyl-1-pyrophosphate-independent salvage of purines in cultured Chinese hamster lung fibroblasts.
A variant clone of cultured chinese hamster lung fibroblasts (V79), selected for resistance to 8-azaguanine (V79 azagrst), although lacking hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8), is able to convert hypoxanthine into IMP via purine-nucleoside phosphorylase (EC 2.4.2.1) and nucleoside kinase. In addition to the phosphoribosylation pathway, we also present evidence for the occurrence of a kinase-mediated pathway of recovery of hypoxanthine in the wild-type cells. The lower rate of formation of IMP in the V79 azagrst cells, apparently correlated with the phosphorylation of the nucleoside, suggests possible differences in the catalytic and/or regulatory properties of nucleoside kinase in the two cell lines. This fact might be of particular relevance in evaluating the mechanisms of resistance to purine analogs displayed by several cell types.
Camici
M
M
Dipartimento di Fisiologia e Biochimica, Laboratori di Biochimica, Pisa, Italy.
Mura
U
U
Cellini
F
F
Del Corso
A
A
Turchi
G
G
Ipata
P L
PL
D000818:Animals; D001375:Azaguanine; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D019271:Hypoxanthine; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism*; D007042:Hypoxanthines / Q000378:metabolism*; D007291:Inosine Monophosphate / Q000096:biosynthesis; D008168:Lung; D010428:Pentosephosphates; D010754:Phosphoribosyl Pyrophosphate; D010770:Phosphotransferases / Q000378:metabolism; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism; D012267:Ribosemonophosphates / Q000378:metabolism
D007042:Hypoxanthines; D010428:Pentosephosphates; D012267:Ribosemonophosphates; D007291:Inosine Monophosphate; C031154:ribose 1-phosphate; D019271:Hypoxanthine; D010754:Phosphoribosyl Pyrophosphate; D011683:Purine-Nucleoside Phosphorylase; D007041:Hypoxanthine Phosphoribosyltransferase; D010770:Phosphotransferases; C021892:nucleoside phosphotransferase; D001375:Azaguanine