title: Dual control of the gua operon of Escherichia coli K12 by adenine and guanine nucleotides.
abstract: The gua operon of Escherichia coli K12 comprises structural genes for the two enzymes, IMP dehydrogenase and GMP synthetase, required for the biosynthesis of GMP from IMP. The specific activities of these enzymes were measured in various purine auxotrophs. GuaA and guaB mutants (guanine-specific) were depressed under conditions of growth limitation by guanine but were repressed by excess guanine. This suggests that formation of the enzymes is normally controlled by a guanine nucleotide. Derepression of the operon in purine-starved pur mutants depended on the type of mutant and on whether adenine or guanine was provided. A purA strain (adenine-specific) and strains with early blocks in purine biosynthesis (purF and purD) did not derepress. PurE or purC strains [5'-phosphoribosyl-5-aminoimidazole (AIR)-accumulating] derepressed only 4-fold. The operon was repressed in purH strains [5'-phosphoribosyl-5-amino-4-imidazolecarboxamide (AICAR)-accumulating] grown with limiting guanine or hypoxanthine, but derepressed by growth with limiting adenine. Two mutants (purA guaA and purA guaB) which can neither synthesize AMP and GMP de novo, nor interconvert them, were isolated. The specific activity of IMP dehydrogenase in one of these strains grown with different concentrations of guanine and adenine revealed that adenine induces tha gua operon whereas guanine represses it. Intracellular purine nucleotide pools wee measured in a purH mutant repressed (guanine-grown) and derepressed (adenine-grown) for IMP dehydrogenase. The guanylate pool was similar under the two growth conditions; however the adenylate pool of the adenine-grown bacteria was two to three times greater than that of the guanine-grown cells. A dual mechanism for regulating expression of the gua operon, involving induction by AMP and repression by GMP, is proposed.
mesh_terms: D000225:Adenine / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000378:metabolism; D019731:Carbon-Nitrogen Ligases; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005796:Genes; D006147:Guanine / Q000378:metabolism* / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000378:metabolism; D007168:IMP Dehydrogenase / Q000378:metabolism; D008025:Ligases / Q000378:metabolism; D009154:Mutation; D009876:Operon / Q000187:drug effects; D011687:Purines / Q000378:metabolism; D012265:Ribonucleotides / Q000378:metabolism
chemical_list: D000227:Adenine Nucleotides; D006150:Guanine Nucleotides; D011687:Purines; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D006147:Guanine; D007168:IMP Dehydrogenase; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C020828:GMP synthase (glutamine-hydrolyzing); C031143:AICA ribonucleotide; D000225:Adenine