Gene Symbol: Glul
Description: glutamate-ammonia ligase
Alias: Glns, glutamine synthetase, Glutamine synthetase (glutamate-ammonia ligase), glutamate decarboxylase, glutamate-ammonia ligase (glutamine synthase), glutamate-ammonia ligase (glutamine synthetase), glutamine synthetase 1
Species: rat
Products:     Glul

Top Publications

  1. Deuel T, Louie M, Lerner A. Glutamine synthetase from rat liver. Purification, properties, and preparation of specific antisera. J Biol Chem. 1978;253:6111-8 pubmed
  2. 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
    ..change; in contrast with what is known in the rat renal cortex, metabolic acidosis markedly diminished the glutamine synthetase activity and protein level, but not the glutamine synthetase mRNA level in the mouse renal cortex...
  3. Mongin A, Hyzinski García M, Vincent M, Keller R. A simple method for measuring intracellular activities of glutamine synthetase and glutaminase in glial cells. Am J Physiol Cell Physiol. 2011;301:C814-22 pubmed publisher
    Here we report and validate a simple method for measuring intracellular activities of glial glutamine synthetase (GS) and glutaminase (GLNase) in intact glial cells...
  4. Deng Y, Xu Z, Xu B, Xu D, Tian Y, Feng W. The protective effects of riluzole on manganese-induced disruption of glutamate transporters and glutamine synthetase in the cultured astrocytes. Biol Trace Elem Res. 2012;148:242-9 pubmed publisher
    ..this accumulation, this study focused on the role of astrocyte glutamate transporters (GluTs) and glutamine synthetase (GS), which have roles in Glu transport and metabolism, respectively...
  5. van de Zande L, Labruyere W, Arnberg A, Wilson R, van den Bogaert A, Das A, et al. Isolation and characterization of the rat glutamine synthetase-encoding gene. Gene. 1990;87:225-32 pubmed
    From a rat genomic library in phage lambda Charon4A, a complete glutamine synthetase-encoding gene was isolated. The gene is 9...
  6. Stanulović V, Garcia de Veas Lovillo R, Labruyere W, Ruijter J, Hakvoort T, Lamers W. The 3'-UTR of the glutamine-synthetase gene interacts specifically with upstream regulatory elements, contains mRNA-instability elements and is involved in glutamine sensing. Biochimie. 2006;88:1255-64 pubmed
    b>Glutamine synthetase (GS) is expressed at various levels in a wide range of tissues, suggesting that a complex network of modules regulates its expression...
  7. Dennis S, Lai J, Clark J. The distribution of glutamine synthetase in subcellular fractions of rat brain. Brain Res. 1980;197:469-75 pubmed
    The subcellular localization of glutamine synthetase, an enzyme fundamental to the compartmentation of glutamate hypothesis, was investigated using brain tissue of adult rats...
  8. Seyama S, Kuroda Y, Katunuma N. Purification and comparison of glutamine synthetase from rat and chick livers. J Biochem. 1972;72:1017-27 pubmed
  9. Schneid C, Darquy S, Cynober L, Reach G, De Bandt J. Effects of ornithine alpha-ketoglutarate on insulin secretion in rat pancreatic islets: implication of nitric oxide synthase and glutamine synthetase pathways. Br J Nutr. 2003;89:249-57 pubmed
    ..A better understanding of OKG insulino-secretory properties and its mechanisms of action are a prerequisite for its use in insulin-compromised situations. ..

More Information


  1. Gaunitz F, Heise K, Schumann R, Gebhardt R. Glucocorticoid induced expression of glutamine synthetase in hepatoma cells. Biochem Biophys Res Commun. 2002;296:1026-32 pubmed
    The enzyme glutamine synthetase (GS) ranks as one of the most remarkable glucocorticoid-inducible vertebrate genes. However, little is known about the responsible DNA elements and the mode of glucocorticoid action...
  2. Ahmedli N, Gribanova Y, Njoku C, Naidu A, Young A, Mendoza E, et al. Dynamics of the rhomboid-like protein RHBDD2 expression in mouse retina and involvement of its human ortholog in retinitis pigmentosa. J Biol Chem. 2013;288:9742-54 pubmed publisher
    ..Our findings suggest that the RHBDD2 protein plays important roles in the development and normal function of the retina. ..
  3. Herrero M, Remesar X, Blade C, Arola L. Muscle amino acid pattern in obese rats. Int J Obes Relat Metab Disord. 1997;21:698-703 pubmed
    ..remained unchanged in these animals and they showed an increased activity in alanine aminotransferase and glutamine synthetase. The leg muscle of the diet-obese rats took up several amino acids (Ala, Arg and Val) or released others (..
  4. Gorg B, Wettstein M, Metzger S, Schliess F, Haussinger D. Lipopolysaccharide-induced tyrosine nitration and inactivation of hepatic glutamine synthetase in the rat. Hepatology. 2005;41:1065-73 pubmed
    b>Glutamine synthetase (GS) in the liver is restricted to a small perivenous hepatocyte population and plays an important role in the scavenging of ammonia that has escaped the periportal urea-synthesizing compartment...
  5. Smith C, Wilson N, Louw A, Myburgh K. Illuminating the interrelated immune and endocrine adaptations after multiple exposures to short immobilization stress by in vivo blocking of IL-6. Am J Physiol Regul Integr Comp Physiol. 2007;292:R1439-47 pubmed
    ..receptors (GR) and activities of glucocorticoid-inducible enzymes (tyrosine aminotransferase and glutamine synthetase) in muscle and liver...
  6. Chowdhury G, Gupta M, Gibson K, Patel A, Behar K. Altered cerebral glucose and acetate metabolism in succinic semialdehyde dehydrogenase-deficient mice: evidence for glial dysfunction and reduced glutamate/glutamine cycling. J Neurochem. 2007;103:2077-91 pubmed
    ..Our findings indicate that SSADH deficiency is associated with major alterations in glutamate and glutamine metabolism in glia and neurons with surprisingly lesser effects on GABA synthesis. ..
  7. Vermeulen T, Gorg B, Vogl T, Wolf M, Varga G, Toutain A, et al. Glutamine synthetase is essential for proliferation of fetal skin fibroblasts. Arch Biochem Biophys. 2008;478:96-102 pubmed publisher
    Background. Glutamine synthetase (GS) is ubiquitously expressed in the human and plays a major role for many metabolic pathways. However, little is known about its role during the fetal period. Methods...
  8. Eid T, Ghosh A, Wang Y, Beckström H, Zaveri H, Lee T, et al. Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats. Brain. 2008;131:2061-70 pubmed publisher
    ..We recently reported that the glutamate-metabolizing enzyme glutamine synthetase is deficient in the hippocampus in patients with MTLE, and we postulated that this deficiency is critically ..
  9. Olkku A, Mahonen A. Wnt and steroid pathways control glutamate signalling by regulating glutamine synthetase activity in osteoblastic cells. Bone. 2008;43:483-93 pubmed publisher
    ..Glutamate is converted to glutamine by glutamine synthetase (GS), which is therefore able to regulate intracellular concentrations of glutamate...
  10. Liu C, Wu W, Zhang B, Xiang J, Zou J. Temporospatial expression and cellular localization of glutamine synthetase following traumatic spinal cord injury in adult rats. Mol Med Rep. 2013;7:1431-6 pubmed publisher
    b>Glutamine synthetase (GS) is an enzyme involved in an endogenous mechanism of protection against glutamate neurotoxicity and is important in the regulation of astrocyte migration...
  11. Fernandes S, Dringen R, Lawen A, Robinson S. Neurones express glutamine synthetase when deprived of glutamine or interaction with astrocytes. J Neurochem. 2010;114:1527-36 pubmed publisher
    b>Glutamine synthetase (GS) forms glutamine by catalyzing the ATP-dependent amidation of glutamate. In healthy brains, GS is restricted to astrocytes but in Alzheimer's disease and cell culture, GS has been detected in neurones...
  12. Ward H, Bradford H. Relative activities of glutamine synthetase and glutaminase in mammalian synaptosomes. J Neurochem. 1979;33:339-42 pubmed
  13. Krstic R, Nicolas D. Light and electron microscopic immunocytochemical localization of glutamine synthetase in the superficial pineal gland of the rat. Acta Histochem. 1992;93:382-7 pubmed
    b>Glutamine synthetase (L-glutamate:ammonia ligase; EC 6.3.1...
  14. Carter C. Reduced GABA transaminase activity in the Huntington's disease putamen. Neurosci Lett. 1984;48:339-42 pubmed
    ..In both cases, the reduction in GABA transaminase activity is comparable with the reduction in glutamate decarboxylase activity, supporting the suspected localization of this enzyme to GABA neurones within the basal ganglia.
  15. Tate S, Leu F, Meister A. Rat liver glutamine synthetase. Preparation, properties, and mechanism of inhibition by carbamyl phosphate. J Biol Chem. 1972;247:5312-21 pubmed
  16. Castegna A, Aksenov M, Aksenova M, Thongboonkerd V, Klein J, Pierce W, et al. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part I: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. Free Radic Biol Med. 2002;33:562-71 pubmed
    ..Proteomics offers a rapid means of identifying oxidatively modified proteins in aging and age-related neurodegenerative disorders without the limitations of the immunochemical detection method. ..
  17. Krajewski W, Collins R, Holmberg Schiavone L, Jones T, Karlberg T, Mowbray S. Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. J Mol Biol. 2008;375:217-28 pubmed
    b>Glutamine synthetase (GS) catalyzes the ligation of glutamate and ammonia to form glutamine, with concomitant hydrolysis of ATP...
  18. Sun Y, Ou Y, Cheng M, Ruan Y, van der Hoorn F. Binding of nickel to testicular glutamate-ammonia ligase inhibits its enzymatic activity. Mol Reprod Dev. 2011;78:104-15 pubmed publisher
    ..We identified glutamate-ammonia ligase (GLUL) as a prominent nickel-binding protein by mass spectrometry...
  19. Zou J, Wang Y, Mu H, Xiang J, Wu W, Zhang B, et al. Down-regulation of glutamine synthetase enhances migration of rat astrocytes after in vitro injury. Neurochem Int. 2011;58:404-13 pubmed publisher
    ..b>Glutamine synthetase (GS) is highly expressed by astrocytes, and serves a neuroprotective function by converting cytotoxic ..
  20. Yu J, Zhong Y, Shen X, Cheng Y, Qi J, Wang J. In vitro effect of adenosine A2A receptor antagonist SCH 442416 on the expression of glutamine synthetase and glutamate aspartate transporter in rat retinal Müller cells at elevated hydrostatic pressure. Oncol Rep. 2012;27:748-52 pubmed publisher
    ..was to investigate the effect of an adenosine A2A receptor antagonist on the expression of glutamine synthetase (GS) and glutamate aspartate transporter (GLAST) in rat retinal Müller cells at elevated ..
  21. van de Zande L, Labruyere W, Smaling M, Moorman A, Wilson R, Charles R, et al. Nucleotide sequence of rat glutamine synthetase mRNA. Nucleic Acids Res. 1988;16:7726 pubmed
  22. Clinkenbeard E, Butler J, Spear B. Pericentral activity of alpha-fetoprotein enhancer 3 and glutamine synthetase upstream enhancer in the adult liver are regulated by ?-catenin in mice. Hepatology. 2012;56:1892-901 pubmed publisher
    ..Here, using transgenic mice, we show that the upstream enhancer of the rat glutamine synthetase gene is also active, specifically in pericentral regions...
  23. Robin M, Palfreyman M, Zraika M, Schechter P. An analysis of the cortical and striatal involvement in dyskinesia induced in rats by intracerebral injection of GABA-transaminase inhibitors and picrotoxin. Eur J Pharmacol. 1980;62:319-27 pubmed
    ..These findings suggest that interference with gabaergic function in the striatum is not necessary for the production of the dyskinetic syndrome and that this syndrome may be a cortically induced phenomenon. ..
  24. da Silva R, Levillain O, Brosnan J, Araneda S, Brosnan M. The effect of portacaval anastomosis on the expression of glutamine synthetase and ornithine aminotransferase in perivenous hepatocytes. Can J Physiol Pharmacol. 2013;91:362-8 pubmed publisher
    There is functional zonation of metabolism across the liver acinus, with glutamine synthetase restricted to a narrow band of cells around the terminal hepatic venules...
  25. Wang Y, Sun M, Hou Q, Parpura V. Hyposmolality differentially and spatiotemporally modulates levels of glutamine synthetase and serine racemase in rat supraoptic nucleus. Glia. 2013;61:529-38 pubmed publisher
    ..of HOC in vivo, whereas at an early stage there was a transient increase in level of the astrocyte-specific glutamine synthetase (GS)...
  26. Foster A, Whetsell W, Bird E, Schwarcz R. Quinolinic acid phosphoribosyltransferase in human and rat brain: activity in Huntington's disease and in quinolinate-lesioned rat striatum. Brain Res. 1985;336:207-14 pubmed
    ..The results indicate that QPRT activity increases in response to specific neurodegenerative events.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  27. Mill J, Mearow K, Purohit H, Haleem Smith H, King R, Freese E. Cloning and functional characterization of the rat glutamine synthetase gene. Brain Res Mol Brain Res. 1991;9:197-207 pubmed
    b>Glutamine synthetase catalyzes the formation of glutamine from glutamate and ammonia. It plays a central role in both amino acid neurotransmitter metabolism and ammonia detoxification in the central nervous system...
  28. Gunnersen D, Haley B. Detection of glutamine synthetase in the cerebrospinal fluid of Alzheimer diseased patients: a potential diagnostic biochemical marker. Proc Natl Acad Sci U S A. 1992;89:11949-53 pubmed
    ..This protein was identified as glutamine synthetase [GS; glutamate-ammonia ligase; L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1...
  29. Jiang E, Yan X, Weng H. Glial glutamate transporter and glutamine synthetase regulate GABAergic synaptic strength in the spinal dorsal horn. J Neurochem. 2012;121:526-36 pubmed publisher
    ..We investigated the role of glial glutamate transporters (GLT-1 and GLAST) and glutamine synthetase in maintaining GABAergic synaptic activity in the spinal dorsal horn...
  30. DeMarco V, Dyess K, Strauss D, West C, Neu J. Inhibition of glutamine synthetase decreases proliferation of cultured rat intestinal epithelial cells. J Nutr. 1999;129:57-62 pubmed
    The importance of glutamine synthetase (GS) for cell proliferation was examined in rat intestinal crypt cells (IEC-6) by inhibiting its activity with 10 mmol/L methionine sulfoximine (MS) at varying extracellular glutamine (Q) ..
  31. Zou J, Wang Y, Dou F, Lu H, Ma Z, Lu P, et al. Glutamine synthetase down-regulation reduces astrocyte protection against glutamate excitotoxicity to neurons. Neurochem Int. 2010;56:577-84 pubmed publisher
    ..Although the role of astrocyte glutamate transporters in glutamate clearance is well illustrated, the role of glutamine synthetase (GS) that influences this process remains to be elucidated...
  32. Gaunitz F, Heise K, Gebhardt R. A silencer element in the first intron of the glutamine synthetase gene represses induction by glucocorticoids. Mol Endocrinol. 2004;18:63-9 pubmed
    The enzyme glutamine synthetase (GS) ranks as one of the most remarkable glucocorticoid-inducible mammalian genes. In many tissues and cell lines, the synthetic glucocorticoid dexamethasone alone increases GS expression several fold...
  33. Barnett N, Pow D, Robinson S. Inhibition of Müller cell glutamine synthetase rapidly impairs the retinal response to light. Glia. 2000;30:64-73 pubmed
    ..The glutamine synthetase inhibitor methionine sulfoximine, when injected intraocularly in Wistar rats, caused a time- and dose-..
  34. Norenberg M, Martinez Hernandez A. Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 1979;161:303-10 pubmed
    The distribution of glutamine synthetase was determined in rat brain by ultrastructural immunocytochemistry. Except for trace amounts in a rare indeterminate glial cell, all the reaction product was located in astrocytes...
  35. 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
    ..We investigated whether a deficiency in glutamine synthetase, a key enzyme in catabolism of extracellular glutamate in the brain, could explain the perturbed glutamate ..
  36. Iida I, Johkura K, Teng R, Kubota S, Cui L, Zhao X, et al. Immunohistochemical localization of hepatocyte growth factor activator (HGFA) in developing mouse liver tissues. Heterogeneous distribution of HGFA protein. J Histochem Cytochem. 2003;51:1139-49 pubmed
    ..These results suggest that HGFA proteins are produced in the hepatocytes surrounding the efferent hepatic veins in the mouse and that development of the unique distributing pattern takes place postnatally. ..
  37. Takumi Y, Matsubara A, Danbolt N, Laake J, Storm Mathisen J, Usami S, et al. Discrete cellular and subcellular localization of glutamine synthetase and the glutamate transporter GLAST in the rat vestibular end organ. Neuroscience. 1997;79:1137-44 pubmed this site of the high affinity glutamate transporter GLAST and glutamate metabolizing enzyme glutamine synthetase. Confocal microscopy revealed that GLAST and glutamine synthetase were co-localized in supporting cells ..
  38. Nasreen Z, Jameel T, Hasan A, Parveen N, Sadasivudu B. Glutamate decarboxylase and GABA aminotransferase levels in different regions of rat brain on the onset of Leptazol induced convulsions. Neurochem Res. 2012;37:202-4 pubmed publisher
    The activities of Glutamate decarboxylase (GAD) and Gamma aminobutyric acid (GABA) were studied in three regions of rat brain in heightened neuronal activity resulting in convulsions by Leptazol...
  39. Acosta G, Fernández M, Roselló D, Tomaro M, Balestrasse K, Lemberg A. Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats. World J Gastroenterol. 2009;15:2893-9 pubmed
    To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension...
  40. Danielyan L, Zellmer S, Sickinger S, Tolstonog G, Salvetter J, Lourhmati A, et al. Keratinocytes as depository of ammonium-inducible glutamine synthetase: age- and anatomy-dependent distribution in human and rat skin. PLoS ONE. 2009;4:e4416 pubmed publisher
    ..However, the age-dependent and regional peculiarities of distribution of glutamine synthetase (GS), an enzyme responsible for generation of glutamine, and factors regulating its enzymatic activity in ..
  41. Steffek A, McCullumsmith R, Haroutunian V, Meador Woodruff J. Cortical expression of glial fibrillary acidic protein and glutamine synthetase is decreased in schizophrenia. Schizophr Res. 2008;103:71-82 pubmed publisher
    ..We investigated the hypothesis that the astrocytic enzyme glutamine synthetase, involved in maintaining the glutamate-glutamine cycle, and the cytoskeletal molecule glial fibrillary ..
  42. Shen X, Xu G. [Effect of interleukin-1 beta on glutamine synthetase in rat retinal Müller cell under high glucose conditions]. Zhonghua Yan Ke Za Zhi. 2007;43:744-9 pubmed
    To investigate the effect of cytokine interleukin-1 beta (IL-1 beta) on the glutamine synthetase (GS) in retinal Müller cell under high glucose conditions and its possible mechanism...
  43. Yamaguchi Y, Miyagi Y, Baba H. Two-dimensional electrophoresis with cationic detergents: a powerful tool for the proteomic analysis of myelin proteins. Part 2: analytical aspects. J Neurosci Res. 2008;86:766-75 pubmed
  44. van der Hel W, Hessel E, Bos I, Mulder S, Verlinde S, van Eijsden P, et al. Persistent reduction of hippocampal glutamine synthetase expression after status epilepticus in immature rats. Eur J Neurosci. 2014;40:3711-9 pubmed publisher
    ..end-folium sclerosis), a common feature in patients with MTS, was accompanied by a progressively decreased glutamine synthetase (GS)-immunoreactivity from 2 (-15%) to 19 weeks (-33.5%) after SE...
  45. Lehmann C, Bette S, Engele J. High extracellular glutamate modulates expression of glutamate transporters and glutamine synthetase in cultured astrocytes. Brain Res. 2009;1297:1-8 pubmed publisher
    ..GLT-1 and GLAST, and subsequently convert the incorporated glutamate into glutamine by the enzyme, glutamine synthetase (GS)...