Nature of 6-methylpurine inhibition and characterization of two 6-methylpurine-resistant mutants of Neurospora crassa.
6-Methylpurine, an analog of adenine, inhibits the growth of Neurospora crassa. From kinetic studies it was found that 6-methylpurine is converted to its nucleotide form by adenine phosphoribosyltransferase (EC 2.4.2.7), and inhibits the de novo purine biosynthesis. Adenine relieves the growth inhibition caused by 6-methylpurine, whereas hypoxanthine is not very effective. Studies dealing with hypoxanthine utilization in the presence of 6-methylpurine indicated a severely reduced uptake of hypoxanthine and a general slowdown in its further metabolism. Two mutants (Mepr-3 and Mepr-10) which are resistant to 6-methylpurine were characterized. Studies of purine base uptake and the in vivo and in vitro conversion to nucleotides indicated that Mepr-10 may be an adenine phosphoribosyltransferase-defective mutant, whereas Mepr-3 may be a mutant with altered feedback response to 6-methylpurine. Both mutants showed a severely lowered hypoxanthine phosphoribosyltransferase activity, but because 6-methylpurine did not have any effect on the conversion of hypoxanthine to IMP in the wild type, it was concluded that 6-methylpurine resistance in these mutants cannot be due to lowered hypoxanthine phosphoribosyltransferase activity, but rather that the lowering of enzyme activity may be a secondary effect.
D000227:Adenine Nucleotides / Q000096:biosynthesis; D000228:Adenine Phosphoribosyltransferase / Q000378:metabolism; D001693:Biological Transport, Active; D004352:Drug Resistance, Microbial; D005796:Genes; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D007042:Hypoxanthines / Q000378:metabolism; D009154:Mutation; D009491:Neurospora / Q000187:drug effects*; D009492:Neurospora crassa / Q000187:drug effects*; D011687:Purines / Q000378:metabolism* / Q000494:pharmacology*
D000227:Adenine Nucleotides; D007042:Hypoxanthines; D011687:Purines; C016588:6-methylpurine; D000228:Adenine Phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase