title: Covalent modification of bacterial glutamine synthetase: physiological significance.
abstract: Stadtman, Holzer and their colleagues (reviewed in Stadtman and Ginsburg 1974) demonstrated that the enzyme glutamine synthetase (GS) [(L-glutamate: ammonia ligase (ADP-forming), EC 6.3.1.2] is covalently modified by adenylylation in a variety of bacterial genera and that the modification is reversible. These studies further indicated that adenylylated GS is the less active form in vitro. To assess the physiological significance of adenylylation of GS we have determined the growth defects of mutant strains (glnE) of S. typhimurium that are unable to modify GS and we have determined the basis for these growth defects. The glnE strains, which lack GS adenylyl transferase activity (ATP: [L-glutamate: ammonia ligase (ADP-forming)] adenylyltransferase, EC 2.7.7.42), show a large growth defect specifically upon shift from a nitrogen-limited growth medium to medium containing excess ammonium (NH4+). The growth defect appears to be due to very high catalytic activity of GS after shift, which lowers the intracellular glutamate pool to approximately 10% that under preshift conditions. Consistent with this view, recovery of a rapid growth rate on NH4+ is accompanied by an increase in the glutamate pool. The glnE strains have normal ATP pools after shift. They synthesize very large amounts of glutamine and excrete glutamine into the medium, but excess glutamine does not seem to inhibit growth. We hypothesize that a major function for adenylylation of bacterial GS is to protect the cellular glutamate pool upon shift to NH4+ -excess conditions and thereby to allow rapid growth.
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism* / Q000502:physiology; D009713:Nucleotidyltransferases / Q000235:genetics / Q000502:physiology; D011499:Protein Processing, Post-Translational; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D000644:Quaternary Ammonium Compounds; D009713:Nucleotidyltransferases; C020658:glutamine-synthetase adenylyltransferase; D005974:Glutamate-Ammonia Ligase