title: Effects of benzimidazole on the purine and pyrimidine metabolism of yeast.
abstract: Yeast cells inhibited by benzimidazole accumulate hypoxanthine with associated efflux of xanthine. Unlike control cells, inhibited cells contain no detectable free UMP and CMP. Benzimidazole decreases uptake of [8-14C]hypoxanthine into the intracellular pool of hypoxanthine and xanthine but causes radioactive xanthine to accumulate in the medium. In inhibited cultures there is a threefold increase in incorporation of [8-14C]hypoxanthine into the total (intracellular plus extracellular) xanthine. Uptake of [8-14C]hypoxanthine into free nucleotides and into bound adenine and guanine was inhibited by 70%. Uptake of [U-14C]glycine into IMP, AMP, GMP, DNA and RNA was also substantially decreased. Incorporation of [2-14C]uracil into the intracellular uracil pool was inhibited by 30% and into free uridine and cytidine by over 90%. Benzimidazole inhibited incorporation of [8-3H]IMP into AMP and GMP, and decreased substantially the activity of glutamine-amidophosphoribosyltransferase (EC 2.4.2.14). Yeast cultures were shown to N-ribotylate benzimidazole. Results are consistent with benzimidazole inhibiting yeast growth by competing for P-rib-PP and so depriving other ribotylation processes such as the 'salvage' pathways and de novo synthesis of purines and pyrimidines.
mesh_terms: D000582:Amidophosphoribosyltransferase / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology*; D005656:Fungal Proteins / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007042:Hypoxanthines / Q000378:metabolism; D007291:Inosine Monophosphate / Q000378:metabolism; D011685:Purine Nucleotides / Q000378:metabolism; D011687:Purines / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D014500:Uracil Nucleotides / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D005656:Fungal Proteins; D007042:Hypoxanthines; D011685:Purine Nucleotides; D011687:Purines; D011743:Pyrimidines; D014500:Uracil Nucleotides; D014970:Xanthines; D007291:Inosine Monophosphate; D000582:Amidophosphoribosyltransferase; D005998:Glycine