title: Mechanism of inhibition of phosphoribosylation of 5-fluorouracil by purines.
abstract: The mechanism of the abolishment of the cytotoxicity of 5-flurouracil by purines in L5178Y cells was determined by using phosphoribosylation enzymes for both 5-fluorouracil and hypoxanthine. Hypoxanthine inhibited the phosphoribosylation of 5-fluorouracil in the presence of both enzymes, but no inhibition by hypoxanthine was found without hypoxanthine phosphoribosyltransferase or at a high concentration of 5-phosphoribosyl 1-pyrophosphate (PRPP). Hypoxanthine, adenine and inosine decreased the intracellular concentration of PRPP to less than one-tenth of that of the control. These results suggest that 5-fluorouracil is activated directly to its nucleotide, 5-fluorouridine 5'-monophosphate, by the phosphoribosylation enzyme and that the inhibition of activation by purines is due to depletion of PRPP.
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005472:Fluorouracil / Q000378:metabolism* / Q000633:toxicity; D051379:Mice; D010430:Pentosyltransferases / Q000378:metabolism*; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism; D011687:Purines / Q000494:pharmacology*
chemical_list: D011687:Purines; D010754:Phosphoribosyl Pyrophosphate; D010430:Pentosyltransferases; C022484:purine phosphoribosyltransferase; C022500:pyrimidine phosphoribosyltransferase; D005472:Fluorouracil