glutamate ammonia ligase

Summary

Summary: An enzyme that catalyzes the conversion of ATP, L-glutamate, and NH3 to ADP, orthophosphate, and L-glutamine. It also acts more slowly on 4-methylene-L-glutamate. (From Enzyme Nomenclature, 1992) EC 6.3.1.2.

Top Publications

  1. Grassi F, Moretto N, Rivetti C, Cellai S, Betti M, Marquez A, et al. Structural and functional properties of lengsin, a pseudo-glutamine synthetase in the transparent human lens. Biochem Biophys Res Commun. 2006;350:424-9 pubmed
  2. Rosati A, Marconi S, Pollo B, Tomassini A, Lovato L, Maderna E, et al. Epilepsy in glioblastoma multiforme: correlation with glutamine synthetase levels. J Neurooncol. 2009;93:319-24 pubmed publisher
    ..This study suggests that seizures in GBM are coupled with a highly localized enzyme deficiency. The manipulation of GS activity might constitute a novel principle for inhibiting seizures in patients with glioma epilepsy. ..
  3. Haberle J, Gorg B, Rutsch F, Schmidt E, Toutain A, Benoist J, et al. Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med. 2005;353:1926-33 pubmed
    ..Studies that used immortalized lymphocytes expressing R324C glutamine synthetase (R324C-GS) and COS7 cells expressing R341C-GS suggest that these mutations are associated with reduced glutamine synthetase activity. ..
  4. Eid T, Williamson A, Lee T, PETROFF O, de Lanerolle N. Glutamate and astrocytes--key players in human mesial temporal lobe epilepsy?. Epilepsia. 2008;49 Suppl 2:42-52 pubmed publisher
    ..Here, we assess recent data regarding the glutamate excess in epilepsy, review the role of glutamine synthetase, and discuss the implications of astrocytes in the pathophysiology of MTLE. ..
  5. Steffens M, Huppertz H, Zentner J, Chauzit E, Feuerstein T. Unchanged glutamine synthetase activity and increased NMDA receptor density in epileptic human neocortex: implications for the pathophysiology of epilepsy. Neurochem Int. 2005;47:379-84 pubmed
    ..However, the detection of a significantly reduced enzymatic activity in the epileptic amygdala supports the assumption that the enzyme defect is localized to the epileptic mesial temporal lobe of corresponding patients. ..
  6. Yu H, Yao Y, Liu Y, Jiao R, Jiang W, Zhao G. A complex role of Amycolatopsis mediterranei GlnR in nitrogen metabolism and related antibiotics production. Arch Microbiol. 2007;188:89-96 pubmed
    ..coelicolor glnR did not result in a detectable pleiotrophic effect. We thus suggest that GlnR is a global regulator with a dual functional impact upon nitrogen metabolism and related antibiotics production. ..
  7. Carroll P, Pashley C, Parish T. Functional analysis of GlnE, an essential adenylyl transferase in Mycobacterium tuberculosis. J Bacteriol. 2008;190:4894-902 pubmed publisher
    ..Thus, we have confirmed that the unusual requirement of M. tuberculosis for GlnE adenylylation activity is linked to the activity of GS in the cell...
  8. Odell L, Nilsson M, Gising J, Lagerlund O, Muthas D, Nordqvist A, et al. Functionalized 3-amino-imidazo[1,2-a]pyridines: a novel class of drug-like Mycobacterium tuberculosis glutamine synthetase inhibitors. Bioorg Med Chem Lett. 2009;19:4790-3 pubmed publisher
    ..Compound 4n was found to be the most potent inhibitor (IC(50)=0.38+/-0.02 microM). This compound was significantly more potent than the known inhibitors, l-methionine-SR-sulfoximine and phosphinothricin. ..
  9. Huo Y, Tian Z, Rappas M, Wen J, Chen Y, You C, et al. Protein-induced DNA bending clarifies the architectural organization of the sigma54-dependent glnAp2 promoter. Mol Microbiol. 2006;59:168-80 pubmed
    ..This proposal is further supported by the modelling of activator-promoter DNA-Esigma54 complex. ..
  10. van Straaten H, He Y, van Duist M, Labruyere W, Vermeulen J, van Dijk P, et al. Cellular concentrations of glutamine synthetase in murine organs. Biochem Cell Biol. 2006;84:215-31 pubmed
    ..GS activity in muscle amounted to only 0.4 micromol.g(-1).min(-1). Our findings confirmed the postulated dichotomy between cellular concentration and GS function. ..

Detail Information

Publications62

  1. Grassi F, Moretto N, Rivetti C, Cellai S, Betti M, Marquez A, et al. Structural and functional properties of lengsin, a pseudo-glutamine synthetase in the transparent human lens. Biochem Biophys Res Commun. 2006;350:424-9 pubmed
  2. Rosati A, Marconi S, Pollo B, Tomassini A, Lovato L, Maderna E, et al. Epilepsy in glioblastoma multiforme: correlation with glutamine synthetase levels. J Neurooncol. 2009;93:319-24 pubmed publisher
    ..This study suggests that seizures in GBM are coupled with a highly localized enzyme deficiency. The manipulation of GS activity might constitute a novel principle for inhibiting seizures in patients with glioma epilepsy. ..
  3. Haberle J, Gorg B, Rutsch F, Schmidt E, Toutain A, Benoist J, et al. Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med. 2005;353:1926-33 pubmed
    ..Studies that used immortalized lymphocytes expressing R324C glutamine synthetase (R324C-GS) and COS7 cells expressing R341C-GS suggest that these mutations are associated with reduced glutamine synthetase activity. ..
  4. Eid T, Williamson A, Lee T, PETROFF O, de Lanerolle N. Glutamate and astrocytes--key players in human mesial temporal lobe epilepsy?. Epilepsia. 2008;49 Suppl 2:42-52 pubmed publisher
    ..Here, we assess recent data regarding the glutamate excess in epilepsy, review the role of glutamine synthetase, and discuss the implications of astrocytes in the pathophysiology of MTLE. ..
  5. Steffens M, Huppertz H, Zentner J, Chauzit E, Feuerstein T. Unchanged glutamine synthetase activity and increased NMDA receptor density in epileptic human neocortex: implications for the pathophysiology of epilepsy. Neurochem Int. 2005;47:379-84 pubmed
    ..However, the detection of a significantly reduced enzymatic activity in the epileptic amygdala supports the assumption that the enzyme defect is localized to the epileptic mesial temporal lobe of corresponding patients. ..
  6. Yu H, Yao Y, Liu Y, Jiao R, Jiang W, Zhao G. A complex role of Amycolatopsis mediterranei GlnR in nitrogen metabolism and related antibiotics production. Arch Microbiol. 2007;188:89-96 pubmed
    ..coelicolor glnR did not result in a detectable pleiotrophic effect. We thus suggest that GlnR is a global regulator with a dual functional impact upon nitrogen metabolism and related antibiotics production. ..
  7. Carroll P, Pashley C, Parish T. Functional analysis of GlnE, an essential adenylyl transferase in Mycobacterium tuberculosis. J Bacteriol. 2008;190:4894-902 pubmed publisher
    ..Thus, we have confirmed that the unusual requirement of M. tuberculosis for GlnE adenylylation activity is linked to the activity of GS in the cell...
  8. Odell L, Nilsson M, Gising J, Lagerlund O, Muthas D, Nordqvist A, et al. Functionalized 3-amino-imidazo[1,2-a]pyridines: a novel class of drug-like Mycobacterium tuberculosis glutamine synthetase inhibitors. Bioorg Med Chem Lett. 2009;19:4790-3 pubmed publisher
    ..Compound 4n was found to be the most potent inhibitor (IC(50)=0.38+/-0.02 microM). This compound was significantly more potent than the known inhibitors, l-methionine-SR-sulfoximine and phosphinothricin. ..
  9. Huo Y, Tian Z, Rappas M, Wen J, Chen Y, You C, et al. Protein-induced DNA bending clarifies the architectural organization of the sigma54-dependent glnAp2 promoter. Mol Microbiol. 2006;59:168-80 pubmed
    ..This proposal is further supported by the modelling of activator-promoter DNA-Esigma54 complex. ..
  10. van Straaten H, He Y, van Duist M, Labruyere W, Vermeulen J, van Dijk P, et al. Cellular concentrations of glutamine synthetase in murine organs. Biochem Cell Biol. 2006;84:215-31 pubmed
    ..GS activity in muscle amounted to only 0.4 micromol.g(-1).min(-1). Our findings confirmed the postulated dichotomy between cellular concentration and GS function. ..
  11. Allodi S, Bressan C, Carvalho S, Cavalcante L. Regionally specific distribution of the binding of anti-glutamine synthetase and anti-S100 antibodies and of Datura stramonium lectin in glial domains of the optic lobe of the giant prawn. Glia. 2006;53:612-20 pubmed
  12. Burbaeva G, Boksha I, Tereshkina E, Savushkina O, Starodubtseva L, Turishcheva M. Glutamate metabolizing enzymes in prefrontal cortex of Alzheimer's disease patients. Neurochem Res. 2005;30:1443-51 pubmed
    ..The results may suggest for the pathological interruption of regulatory relations between distinct enzymes of glutamate metabolism in brain of AD patients. ..
  13. Harth G, Maslesa Galic S, Tullius M, Horwitz M. All four Mycobacterium tuberculosis glnA genes encode glutamine synthetase activities but only GlnA1 is abundantly expressed and essential for bacterial homeostasis. Mol Microbiol. 2005;58:1157-72 pubmed
    ..tuberculosis drugs. ..
  14. Erikson K, Dorman D, Lash L, Aschner M. Manganese inhalation by rhesus monkeys is associated with brain regional changes in biomarkers of neurotoxicity. Toxicol Sci. 2007;97:459-66 pubmed
    ..g., GSH was increased in the frontal cortex and decreased in the caudate despite two- to threefold increases in Mn concentrations in these regions). ..
  15. Bernard S, M ller A, Dionisio G, Kichey T, Jahn T, Dubois F, et al. Gene expression, cellular localisation and function of glutamine synthetase isozymes in wheat (Triticum aestivum L.). Plant Mol Biol. 2008;67:89-105 pubmed publisher
    ..Use of this genetic variation should inform future efforts to modulate this enzyme for pre-breeding efforts to improve nitrogen use in wheat...
  16. Amon J, Bräu T, Grimrath A, Hänssler E, Hasselt K, Höller M, et al. Nitrogen control in Mycobacterium smegmatis: nitrogen-dependent expression of ammonium transport and assimilation proteins depends on the OmpR-type regulator GlnR. J Bacteriol. 2008;190:7108-16 pubmed publisher
    ..The GlnR protein binds specifically to the corresponding promoter sequences and functions as an activator of transcription when cells are subjected to nitrogen starvation. ..
  17. Harper C, Hayward D, Wiid I, van Helden P. Regulation of nitrogen metabolism in Mycobacterium tuberculosis: a comparison with mechanisms in Corynebacterium glutamicum and Streptomyces coelicolor. IUBMB Life. 2008;60:643-50 pubmed publisher
    ..glutamicum and S. coelicolor is made to identify similarities with M. tuberculosis on both a genomic and proteomic level. This may provide insight into a potential global mechanism of nitrogen control in Mycobacterium tuberculosis. ..
  18. Bernard S, Habash D. The importance of cytosolic glutamine synthetase in nitrogen assimilation and recycling. New Phytol. 2009;182:608-20 pubmed publisher
    ..The diverse physiological roles of cytosolic glutamine synthetase isoenzymes are important in relation to current agricultural and ecological issues. ..
  19. Wyatt K, White H, Wang L, Bateman O, Slingsby C, Orlova E, et al. Lengsin is a survivor of an ancient family of class I glutamine synthetases re-engineered by evolution for a role in the vertebrate lens. Structure. 2006;14:1823-34 pubmed
    ..Genes related to Lengsin are also present in the sea urchin, suggesting that this branch of the GS I family, supplanted by GS II enzymes in vertebrates, has an ancient role in metazoans. ..
  20. Shen X, Xu G. Role of IL-1beta on the glutamine synthetase in retinal Müller cells under high glucose conditions. Curr Eye Res. 2009;34:727-36 pubmed
    ..Interleukin-1beta decreases expression of glutamine synthetase via activation of c-Jun. The data suggested that interleukin-1beta may play a role in the development of diabetic retinopathy. ..
  21. Zhang Y, Pohlmann E, Conrad M, Roberts G. The poor growth of Rhodospirillum rubrum mutants lacking PII proteins is due to an excess of glutamine synthetase activity. Mol Microbiol. 2006;61:497-510 pubmed publisher
    ..rubrum mutants lacking P(II) and presumably in mutants of some other organisms with similar genotypes. The result underscores the importance of proper regulation of GS activity for cell growth...
  22. Robertson D, Tartar A. Evolution of glutamine synthetase in heterokonts: evidence for endosymbiotic gene transfer and the early evolution of photosynthesis. Mol Biol Evol. 2006;23:1048-55 pubmed
    ..The lack of GSIII sequences in the oomycetes examined here further suggests that the GSIII gene that functions in the cytosol of photosynthetic heterokonts was replaced by the endosymbiont-derived GSII gene...
  23. Llorca O, Betti M, Gonzalez J, Valencia A, Marquez A, Valpuesta J. The three-dimensional structure of an eukaryotic glutamine synthetase: functional implications of its oligomeric structure. J Struct Biol. 2006;156:469-79 pubmed
    ..All this suggests for the GS-II enzyme an oligomeric structure containing four active sites and four possible regulatory sites, which might point to a complex regulatory behavior. ..
  24. Audard V, Grimber G, Elie C, Radenen B, Audebourg A, Letourneur F, et al. Cholestasis is a marker for hepatocellular carcinomas displaying beta-catenin mutations. J Pathol. 2007;212:345-52 pubmed
    ..In conclusion, we propose that GS immunostaining and a cholestatic pattern are relevant criteria for the identification of HCC with beta-catenin mutations. ..
  25. Clawson M, Bourret A, Benson D. Assessing the phylogeny of Frankia-actinorhizal plant nitrogen-fixing root nodule symbioses with Frankia 16S rRNA and glutamine synthetase gene sequences. Mol Phylogenet Evol. 2004;31:131-8 pubmed
  26. Cadoret A, Ovejero C, Terris B, Souil E, Levy L, Lamers W, et al. New targets of beta-catenin signaling in the liver are involved in the glutamine metabolism. Oncogene. 2002;21:8293-301 pubmed
    ..Because a linkage of the glutamine pathway to hepatocarcinogenesis has already been demonstrated, we propose that regulation of these three genes of glutamine metabolism by beta-catenin is a contributing factor to liver carcinogenesis. ..
  27. Melo P, Lima L, Santos I, Carvalho H, Cullimore J. Expression of the plastid-located glutamine synthetase of Medicago truncatula. Accumulation of the precursor in root nodules reveals an in vivo control at the level of protein import into plastids. Plant Physiol. 2003;132:390-9 pubmed
    ..These results may reflect a regulation of GS2 activity in relation to nitrogen fixation at the level of protein import into nodule plastids. ..
  28. Glévarec G, Bouton S, Jaspard E, Riou M, Cliquet J, Suzuki A, et al. Respective roles of the glutamine synthetase/glutamate synthase cycle and glutamate dehydrogenase in ammonium and amino acid metabolism during germination and post-germinative growth in the model legume Medicago truncatula. Planta. 2004;219:286-97 pubmed
    ..Interestingly, this reaction also produces reducing power (NADH) in organs deprived of photosynthesis. ..
  29. Taira M, Valtersson U, Burkhardt B, Ludwig R. Arabidopsis thaliana GLN2-encoded glutamine synthetase is dual targeted to leaf mitochondria and chloroplasts. Plant Cell. 2004;16:2048-58 pubmed
    ..Therefore, the GLN2 gene product, heretofore labeled plastidic GS-2, functions in both leaf mitochondria and chloroplasts to faciliate ammonium recovery during photorespiration. ..
  30. Eid T, Thomas M, Spencer D, Rundén Pran E, Lai J, Malthankar G, et al. Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. Lancet. 2004;363:28-37 pubmed
    ..Further studies are needed to define the cause, but the loss of glutamine synthetase may provide a new focus for therapeutic interventions in MTLE. ..
  31. Dobson A, Weber S, Dorman D, Lash L, Erikson K, Aschner M. Oxidative stress is induced in the rat brain following repeated inhalation exposure to manganese sulfate. Biol Trace Elem Res. 2003;93:113-26 pubmed
  32. Mommsen T, Busby E, von Schalburg K, Evans J, Osachoff H, Elliott M. Glutamine synthetase in tilapia gastrointestinal tract: zonation, cDNA and induction by cortisol. J Comp Physiol B. 2003;173:419-27 pubmed publisher
    ..Finally, we present evidence for similar abundance of glutamine synthetase transcripts in all regions of rockfish intestine. The physiological significance of the presence of glutamine synthetase in teleostean intestine is discussed...
  33. Reitzer L. Nitrogen assimilation and global regulation in Escherichia coli. Annu Rev Microbiol. 2003;57:155-76 pubmed
    ..Guanosine tetraphosphate appears to control Lrp synthesis. In summary, a network of interacting global regulators that senses different aspects of metabolism integrates nitrogen assimilation with other metabolic processes. ..
  34. Wilhelmsson U, Li L, Pekna M, Berthold C, Blom S, Eliasson C, et al. Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J Neurosci. 2004;24:5016-21 pubmed
    ..These findings show a novel role for intermediate filaments in astrocytes and implicate reactive astrocytes as potent inhibitors of neuroregeneration. ..
  35. Conjard A, Komaty O, Delage H, Boghossian M, Martin M, Ferrier B, et al. Inhibition of glutamine synthetase in the mouse kidney: a novel mechanism of adaptation to metabolic acidosis. J Biol Chem. 2003;278:38159-66 pubmed
    ..Furthermore, they show that, in rodents, the regulation of renal glutamine synthetase is species-specific. ..