Inhibition of de novo purine biosynthesis and interconversion by 6-methylpurine in Escherichia coli.
The inhibition of Escherichia coli strain B and strain W-11 by 6-methylpurine depended on the formation of 6-methylpurine ribonucleotide by the action of adenine phosphoribosyltransferase (AMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.7). 6-Methylpurine ribonucleotide inhibited the de novo synthesis of purines, presumably via pseudofeedback inhibition of phosphoribosylpyrophosphate amidotransferase (EC 2.4.2.14). The same mechanism accounted for its inhibition of adenylosuccinate synthetase [IMP: l-aspartate ligase (GDP), EC 6.3.4.4]. Adenine and 6-methylaminopurine prevented inhibition by competing for the action of adenine phosphoribosyltransferase. In addition, adenine reversed this inhibition by replenishing the AMP to bypass both sites of inhibition. Nonproliferating suspensions of strain B-94, which lacked adenylosuccinate lyase (EC 4.3.2.2), converted exogenous hypoxanthine and aspartate to succinoadenine derivatives which accumulated in the medium. Compounds which inhibited adenylosuccinate synthetase inhibited accumulation of the succinoadenine derivatives. A method was described for the isolation of mutants which potentially possessed an altered adenylosuccinate synthetase.
D000225:Adenine / Q000494:pharmacology; D002247:Carbon Isotopes; D002854:Chromatography, Paper; D003864:Depression, Chemical; D004586:Electrophoresis; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D005827:Genetics, Microbial; D008025:Ligases / Q000378:metabolism; D008190:Lyases / Q000378:metabolism; D009154:Mutation; D011687:Purines / Q000096:biosynthesis*; D013053:Spectrophotometry; D014166:Transferases / Q000378:metabolism; D014466:Ultraviolet Rays
D002247:Carbon Isotopes; D011687:Purines; D014166:Transferases; D008190:Lyases; D008025:Ligases; D000225:Adenine