The metabolism of 3-deazaguanine and 3-deazaguanosine by human cells in culture.
The metabolism of the purine analogs 3-deazaguanine and 3-deazaguanosine was studied in cultured human cells using radiolabeled tracers, individual enzyme assays, and mutant cell lines. The toxicity of each drug appeared to require conversion to the 5' nucleotide. The base was converted to the nucleotide by hypoxanthine guanine phosphoribosyl transferase. The conversion of the nucleoside to the nucleotide was catalyzed by an unidentified kinase. Purine nucleoside 3-deazaguanosine-5'-monophosphate was converted to its corresponding di- and triphosphate by guanylate kinase. Both the base and the nucleoside were incorporated into DNA but not RNA.
D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D006157:Guanosine Monophosphate / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D012313:RNA / Q000378:metabolism
D006151:Guanosine; C010568:3-deazaguanosine; C010569:3-deazaguanylic acid; D006147:Guanine; D012313:RNA; D006157:Guanosine Monophosphate; D004247:DNA; C010567:3-deazaguanine; D007041:Hypoxanthine Phosphoribosyltransferase