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Gene Review

Gls  -  glutaminase

Mus musculus

Synonyms: 6330442B14, AI314027, B230365M23Rik, GLS, Gls1, ...
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Disease relevance of Gls

  • Our results suggest that inhibition of glutaminase expression using anti-sense technology induces phenotypic changes in Ehrlich ascites tumor cells that allow the development of an effective anti-tumor immune response, which makes the cells unable to develop in vivo tumors [1].
  • Mice bearing the Lewis lung carcinoma showed a high tumour glutaminase activity and significantly higher concentrations of most amino acids than in both the liver and the skeletal muscle of the host [2].
  • AVET-transfected keratinocytes derived from keratinocyte trans- glutaminase negative lamellar ichthyosis patients with a CMV-TGK expression plasmid showed that it is possible to reach a level of total enzyme activity similar to that found in cultured keratinocytes from normal individuals [3].
  • Changes in phosphate-activated glutaminase activities determined in intact cells and isolated mitochondria have been followed during mouse Ehrlich ascites carcinoma development [4].
  • Pseudomonas 7A glutaminase reduced the survival of cells in glutamine-free culture and prevented growth of spheroids [5].

High impact information on Gls

  • The levels of free glutamine in plasma and tissues, and the activities of glutamine synthetase and glutaminase, tended to approach normal values in the last days of life of the tumor-transplanted animals [6].
  • Unlike results reported with glutaminase and asparaginase preparations, the lactate dehydrogenase-elevating virus had no significant influence on plasma clearance of tyrosine phenol-lyase [7].
  • Here we have shown that TNF-alpha is the key cytokine that stimulates extensive microglial glutamate release in an autocrine manner by up-regulating glutaminase to cause excitoneurotoxicity [8].
  • In vivo, mtGSH depletion in B16M-F10 cells was achieved by feeding mice (where the B16M-F10 grew as a solid tumor in the footpad) with an L-glutamine (L-Gln)-enriched diet, which promoted in the tumor cells an increase in glutaminase activity, accumulation of cytosolic L-glutamate, and competitive inhibition of GSH transport into mitochondria [9].
  • We rescued neuronal cell death in vitro by using a glutaminase inhibitor or hemichannel blockers to diminish microglial glutamate release without perturbing the physiological glutamate level [8].

Chemical compound and disease context of Gls


Biological context of Gls


Anatomical context of Gls


Associations of Gls with chemical compounds


Physical interactions of Gls


Other interactions of Gls


Analytical, diagnostic and therapeutic context of Gls

  • Glutaminase had no effect on cell survival in the Lewis lung tumour or in MGH-U1 xenografts, with or without radiation; glutaminase caused dose-dependent growth delay of the KHT tumour, which was additive to that caused by radiation [5].
  • Bacterial glutaminase was shown to be effective in lowering the tumor burden with increased life span of the host [25].
  • Northern blot analysis indicated that two species of glutaminase mRNA were expressed in the spleen, which showed a differential expression pattern during the first 2 days after tumor implantation [26].
  • Phosphate dependent glutaminase enzyme purified from mitochondria of malignant and non malignant ovarian tissue also showed bands of same molecular weight on 10% SDS-PAGE and gave same immunoreactive bands in trans-immunoblot like the purified glutaminase from ascites fluid [27].
  • In several investigations, bacterial glutaminase was found to be a potent therapeutic agent against varieties of tumor, but it showed suppressive effects on haematopoietic systems and inhibitory effects on normal lymphocytic blastogenesis [28].


  1. Ehrlich ascites tumor cells expressing anti-sense glutaminase mRNA lose their capacity to evade the mouse immune system. Segura, J.A., Ruiz-Bellido, M.A., Arenas, M., Lobo, C., Márquez, J., Alonso, F.J. Int. J. Cancer (2001) [Pubmed]
  2. Amino acid metabolism in tumour-bearing mice. Rivera, S., Azcón-Bieto, J., López-Soriano, F.J., Miralpeix, M., Argilés, J.M. Biochem. J. (1988) [Pubmed]
  3. Efficient in vitro transfection of human keratinocytes with an adenovirus-enhanced receptor-mediated system. Huber, M., Limat, A., Wagner, E., Hohl, D. J. Invest. Dermatol. (2000) [Pubmed]
  4. Phosphate-activated glutaminase expression during tumor development. Aledo, J.C., Segura, J.A., Medina, M.A., Alonso, F.J., Núñez de Castro, I., Márquez, J. FEBS Lett. (1994) [Pubmed]
  5. Influence of reduced concentration of L-glutamine on growth and viability of cells in monolayer, in spheroids, and in experimental tumours. Tannock, I.F., Steele, D., Roberts, J. Br. J. Cancer (1986) [Pubmed]
  6. Contribution by host tissues to circulating glutamine in mice inoculated with Ehrlich ascites tumor cells. Quesada, A.R., Medina, M.A., Márquez, J., Sánchez-Jiménez, F.M., Núñez de Castro, I. Cancer Res. (1988) [Pubmed]
  7. Some biological properties and an in vivo evaluation of tyrosine phenol-lyase on growth of B-16 melanoma. Meadows, G.G., DiGiovanni, J., Minor, L., Elmer, G.W. Cancer Res. (1976) [Pubmed]
  8. Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. Takeuchi, H., Jin, S., Wang, J., Zhang, G., Kawanokuchi, J., Kuno, R., Sonobe, Y., Mizuno, T., Suzumura, A. J. Biol. Chem. (2006) [Pubmed]
  9. Bcl-2 and Mn-SOD antisense oligodeoxynucleotides and a glutamine-enriched diet facilitate elimination of highly resistant B16 melanoma cells by tumor necrosis factor-alpha and chemotherapy. Benlloch, M., Mena, S., Ferrer, P., Obrador, E., Asensi, M., Pellicer, J.A., Carretero, J., Ortega, A., Estrela, J.M. J. Biol. Chem. (2006) [Pubmed]
  10. Glutamatergic or GABAergic neuron-specific, long-term expression in neocortical neurons from helper virus-free HSV-1 vectors containing the phosphate-activated glutaminase, vesicular glutamate transporter-1, or glutamic acid decarboxylase promoter. Rasmussen, M., Kong, L., Zhang, G.R., Liu, M., Wang, X., Szabo, G., Curthoys, N.P., Geller, A.I. Brain Res. (2007) [Pubmed]
  11. [13N]Ammonia and L-[amide-13N]glutamine metabolism in glutaminase-sensitive and glutaminase-resistant murine tumors. Rosenspire, K.C., Gelbard, A.S., Cooper, A.J., Schmid, F.A., Roberts, J. Biochim. Biophys. Acta (1985) [Pubmed]
  12. Effect of purified glutaminase from human ascites fluid on experimental tumor bearing mice. Bhattacharya, P., Sett, S., Maity, P. J. Exp. Clin. Cancer Res. (2001) [Pubmed]
  13. Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse. Coleman, M.A., Eisen, J.A., Mohrenweiser, H.W. Genomics (2000) [Pubmed]
  14. A glutaminase (gis) gene maps to mouse chromosome 1, rat chromosome 9, and human chromosome 2. Mock, B., Kozak, C., Seldin, M.F., Ruff, N., D'Hoostelaere, L., Szpirer, C., Levan, G., Seuanez, H., O'Brien, S., Banner, C. Genomics (1989) [Pubmed]
  15. Analysis of glutaminase activity and RNA expression in preimplantation mouse embryos. Chatot, C.L., Lawry, J.R., Germain, B., Ziomek, C.A. Mol. Reprod. Dev. (1997) [Pubmed]
  16. Increased production of extracellular glutamate by the mitochondrial glutaminase following neuronal death. Newcomb, R., Sun, X., Taylor, L., Curthoys, N., Giffard, R.G. J. Biol. Chem. (1997) [Pubmed]
  17. Brain-specific BNIP-2-homology protein Caytaxin relocalises glutaminase to neurite terminals and reduces glutamate levels. Buschdorf, J.P., Li Chew, L., Zhang, B., Cao, Q., Liang, F.Y., Liou, Y.C., Zhou, Y.T., Low, B.C. J. Cell. Sci. (2006) [Pubmed]
  18. Phosphate activated glutaminase activity and glutamine uptake in primary cultures of astrocytes. Schousboe, A., Hertz, L., Svenneby, G., Kvamme, E. J. Neurochem. (1979) [Pubmed]
  19. Studies on the mechanism of the glutamine-dependent reaction catalyzed by asparagine synthetase from mouse pancreas. Milman, H.A., Cooney, D.A., Huang, C.Y. J. Biol. Chem. (1980) [Pubmed]
  20. Kinetics of uptake and activity in mouse liver of glutaminase coupled to desialated orosomucoid. Schmer, G., Holcenberg, J.S., Roberts, J. Biochim. Biophys. Acta (1978) [Pubmed]
  21. A genetic linkage map of rat chromosome 9 with a new locus for variant activity of liver aldehyde oxidase. Kunieda, T., Kobayashi, E., Tachibana, M., Ikadai, H. Exp. Anim. (1999) [Pubmed]
  22. Effect of starvation on glutamine ammoniagenesis and gluconeogenesis in isolated mouse kidney tubules. Conjard, A., Brun, V., Martin, M., Baverel, G., Ferrier, B. Biochem. J. (2002) [Pubmed]
  23. Heat induction of heat shock protein 25 requires cellular glutamine in intestinal epithelial cells. Phanvijhitsiri, K., Musch, M.W., Ropeleski, M.J., Chang, E.B. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  24. Calories and aging alter gene expression for gluconeogenic, glycolytic, and nitrogen-metabolizing enzymes. Dhahbi, J.M., Mote, P.L., Wingo, J., Tillman, J.B., Walford, R.L., Spindler, S.R. Am. J. Physiol. (1999) [Pubmed]
  25. Investigation on glutamine amidohydrolase (EC and glutamine aminotransferase (EC activity in liver and plasma of EAC-bearing mice following glutaminase therapy. Pal, S., Maity, P. Cancer Lett. (1992) [Pubmed]
  26. Early differential expression of two glutaminase mRNAs in mouse spleen after tumor implantation. Aledo, J.C., Segura, J.A., Barbero, L.G., Márquez, J. Cancer Lett. (1998) [Pubmed]
  27. Localization of phosphate dependent glutaminase in ascites fluid of ovarian cancer patient. Bhattacharya, P., Maity, P. Pathol. Oncol. Res. (2000) [Pubmed]
  28. Isolation and purification of phosphate dependent glutaminase from sarcoma-180 tumor and its antineoplastic effects on murine model system. Maity, P., Chakraborty, S., Bhattacharya, P., Sarkar, R. J. Exp. Clin. Cancer Res. (1999) [Pubmed]
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