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Gene Review

GLS  -  glutaminase

Homo sapiens

Synonyms: AAD20, GAC, GAM, GLS1, Glutaminase kidney isoform, mitochondrial, ...
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Disease relevance of GLS

  • In contrast, after onset of acidosis, the level of GA mRNA initially remains unchanged, is then increased 8-fold between 10 and 16 h, and then decreases slightly [1].
  • These data support a possible role for intestinal glutaminase in the pathogenesis of hepatic encephalopathy (HE) and could be a new target for future therapies [2].
  • Human cutaneous melanoma expresses a significant phosphate-dependent glutaminase activity: a comparison with the surrounding skin of the same patient [3].
  • Upon induction, precursor glutaminase accounts for about 25% of total E. coli protein, whereas a lower amount (12%) was achieved for the putative mature protein [4].
  • The first complete sequence of human L-glutaminase was deduced from breast cancer glutaminase cDNA cloned in our laboratory [4].

Psychiatry related information on GLS


High impact information on GLS


Chemical compound and disease context of GLS


Biological context of GLS

  • The human loci for phosphate-activated glutaminase (GLS) and IL9 have previously been mapped to chromosomes 2 and 5, respectively, by analysis of somatic cell hybrid DNAs [15].
  • Glutaminase associates with both PDZ proteins through its C-terminal end; mutagenesis of single amino acids revealed the sequence -ESXV as essential for the interaction [16].
  • The overall nucleotide sequence of hGA has a very high degree of identity with that of the rat kidney-type GA cDNA (77.4%) and the known portion of the cDNA that encodes the 5.0-kb porcine GA mRNA (81.1%) [17].
  • Results obtained from radiation hybrid mapping experiments assigned the K-glutaminase gene to human Chromosome (Chr) 2, and a second locus for L-glutaminase in Chr 12 was identified [18].
  • The kinetics and other properties of phosphate-activated glutaminase have for the first time been studied in the crude mitochondrial fraction (P2 fraction) from human brain [19].

Anatomical context of GLS


Associations of GLS with chemical compounds

  • The enzyme glutaminase in brain is responsible for the synthesis of neurotransmitter glutamate [16].
  • Thus, expression of the isolated hGA cDNA should provide a means to purify large amounts of the mitochondrial glutaminase, a protein that catalyzes a key reaction in the metabolism of glutamine and the synthesis of important excitatory and inhibitory neurotransmitters [17].
  • The level of PCK mRNA is increased with increasing glucose concentration from 0 to 40 mM, whereas the level of GA mRNA is maximal between 3 and 5 mM glucose [1].
  • The use of actinomycin D to measure the half-lives of PCK and GA mRNAs at pH 7.4 and 6.9 indicates that stabilization may fully account for the induction of GA mRNA and contributes to the inductive effects of decreased pH and/or bicarbonate on PCK mRNA [1].
  • Before irradiation, GLS and KYG tumours showed significantly higher rates of 18FDG accumulation compared with NNE tumours (P <0.004 and P <0.001, respectively) [22].

Regulatory relationships of GLS

  • METHODS: Fibroblast-like synoviocytes (FLSs) obtained from RA patients were cultured and stimulated by GLS [23].
  • Elevation of gamma-glutamyltransferase activity in 293 HEK cells constitutively expressing antisense glutaminase mRNA [24].

Other interactions of GLS


Analytical, diagnostic and therapeutic context of GLS

  • By using chromosomal in situ hybridization, we have regionally mapped GLS to 2q32----q34 and IL9 to 5q31----q35 [15].
  • In a novel finding using glutaminase-specific antibodies in combination with flow cytometry and confocal microscopy, glutaminase was shown to be present on the surface of human PMN [20].
  • 78 patients with exfoliation syndrome were examined by one clinician (GLS), and underwent gonioscopy and dilated funduscopy [28].
  • Patients undergoing arthroplasty demonstrated a decrease in serum GLS levels after the operations, but patients undergoing synovectomy did not, reflecting the extent of remaining or reproliferating synovial tissues rich in GLS production [29].
  • Immunoassay systems were used to quantify GLS or cytokine levels in laboratory and clinical samples [30].


  1. Effect of pH and bicarbonate on phosphoenolpyruvate carboxykinase and glutaminase mRNA levels in cultured renal epithelial cells. Kaiser, S., Curthoys, N.P. J. Biol. Chem. (1991) [Pubmed]
  2. Intestinal glutaminase activity is increased in liver cirrhosis and correlates with minimal hepatic encephalopathy. Romero-Gómez, M., Ramos-Guerrero, R., Grande, L., de Terán, L.C., Corpas, R., Camacho, I., Bautista, J.D. J. Hepatol. (2004) [Pubmed]
  3. Human cutaneous melanoma expresses a significant phosphate-dependent glutaminase activity: a comparison with the surrounding skin of the same patient. Zacharias, D.P., Lima, M.M., Souza, A.L., de Abranches Oliveira Santos, I.D., Enokiara, M., Michalany, N., Curi, R. Cell Biochem. Funct. (2003) [Pubmed]
  4. Expression of recombinant human L-glutaminase in Escherichia coli: polyclonal antibodies production and immunological analysis of mouse tissues. Campos, J.A., Aledo, J.C., Segura, J.A., Alonso, F.J., Gómez-Fabre, P.M., Núñez de Castro, I., Márquez, J. Biochim. Biophys. Acta (2003) [Pubmed]
  5. Glutamate-, glutaminase-, and taurine-immunoreactive neurons develop neurofibrillary tangles in Alzheimer's disease. Kowall, N.W., Beal, M.F. Ann. Neurol. (1991) [Pubmed]
  6. Is the neuronal basis of Alzheimer's disease cholinergic or glutamatergic? Palmer, A.M., Gershon, S. FASEB J. (1990) [Pubmed]
  7. Phosphate-activated glutaminase in relation to Huntington's disease and agonal state. Butterworth, J., Yates, C.M., Simpson, J. J. Neurochem. (1983) [Pubmed]
  8. Selective localization of glutaminase in spinal and sensory nerve cells. A potential marker for glutamate neurotransmission. Cangro, C.B., Sweetnam, P.M., Neale, J.H., Haser, W.G., Curthoys, N.P. JAMA (1984) [Pubmed]
  9. Structure of a bacterial pyridoxal 5'-phosphate synthase complex. Strohmeier, M., Raschle, T., Mazurkiewicz, J., Rippe, K., Sinning, I., Fitzpatrick, T.B., Tews, I. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  10. Multiple sclerosis: altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage. Werner, P., Pitt, D., Raine, C.S. Ann. Neurol. (2001) [Pubmed]
  11. Hepatic glutaminase expression: relationship to kidney-type glutaminase and to the urea cycle. Watford, M. FASEB J. (1993) [Pubmed]
  12. Comparison of effects of doxorubicin and radiation on p53-dependent apoptosis in vivo. Hayakawa, K., Hasegawa, M., Kawashima, M., Nakamura, Y., Matsuura, M., Toda, H., Hayakawa, K., Mitsuhashi, N., Niibe, H. Oncol. Rep. (2000) [Pubmed]
  13. Evolutionary relationships of the carbamoylphosphate synthetase genes. van den Hoff, M.J., Jonker, A., Beintema, J.J., Lamers, W.H. J. Mol. Evol. (1995) [Pubmed]
  14. Cortical glutaminase, beta-glucuronidase and glucose utilization in Alzheimer's disease. McGeer, E.G., McGeer, P.L., Akiyama, H., Harrop, R. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. (1989) [Pubmed]
  15. Regional localization of the human glutaminase (GLS) and interleukin-9 (IL9) genes by in situ hybridization. Modi, W.S., Pollock, D.D., Mock, B.A., Banner, C., Renauld, J.C., Van Snick, J. Cytogenet. Cell Genet. (1991) [Pubmed]
  16. The C-terminus of human glutaminase L mediates association with PDZ domain-containing proteins. Olalla, L., Aledo, J.C., Bannenberg, G., Márquez, J. FEBS Lett. (2001) [Pubmed]
  17. Isolation, characterization and expression of a human brain mitochondrial glutaminase cDNA. Holcomb, T., Taylor, L., Trohkimoinen, J., Curthoys, N.P. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  18. Identification of two human glutaminase loci and tissue-specific expression of the two related genes. Aledo, J.C., Gómez-Fabre, P.M., Olalla, L., Márquez, J. Mamm. Genome (2000) [Pubmed]
  19. Phosphate-activated glutaminase in the crude mitochondrial fraction (P2 fraction) from human brain cortex. Svenneby, G., Roberg, B., Hogstad, S., Torgner, I.A., Kvamme, E. J. Neurochem. (1986) [Pubmed]
  20. Granule localization of glutaminase in human neutrophils and the consequence of glutamine utilization for neutrophil activity. Castell, L., Vance, C., Abbott, R., Marquez, J., Eggleton, P. J. Biol. Chem. (2004) [Pubmed]
  21. Lack of expression of the liver-type glutaminase (LGA) mRNA in human malignant gliomas. Szeliga, M., Sidoryk, M., Matyja, E., Kowalczyk, P., Albrecht, J. Neurosci. Lett. (2005) [Pubmed]
  22. Rapid rise in FDG uptake in an irradiated human tumour xenograft. Furuta, M., Hasegawa, M., Hayakawa, K., Yamakawa, M., Ishikawa, H., Nonaka, T., Mitsuhashi, N., Niibe, H. European journal of nuclear medicine. (1997) [Pubmed]
  23. Autocrine induction of gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) and GLS-induced expression of matrix metalloproteinases in rheumatoid arthritis synoviocytes. Muro, H., Waguri-Nagaya, Y., Mukofujiwara, Y., Iwahashi, T., Otsuka, T., Matsui, N., Moriyama, A., Asai, K., Kato, T. Rheumatology (Oxford, England) (1999) [Pubmed]
  24. Elevation of gamma-glutamyltransferase activity in 293 HEK cells constitutively expressing antisense glutaminase mRNA. Wong, K.T., Lee, Y.Y., Brusic, V., Tan, J., Yap, M.G., Nissom, P.M. Metab. Eng. (2005) [Pubmed]
  25. Effect of glutamine-supplemented total parenteral nutrition on the small bowel of septic rats. Ardawi, M.S. Clinical nutrition (Edinburgh, Scotland) (1992) [Pubmed]
  26. Decrease of glutaminase expression by interferon-gamma in human intestinal epithelial cells. Sarantos, P., Abouhamze, Z., Copeland, E.M., Souba, W.W. Ann. Surg. Oncol. (1994) [Pubmed]
  27. Stereological estimates of the basal forebrain cell population in the rat, including neurons containing choline acetyltransferase, glutamic acid decarboxylase or phosphate-activated glutaminase and colocalizing vesicular glutamate transporters. Gritti, I., Henny, P., Galloni, F., Mainville, L., Mariotti, M., Jones, B.E. Neuroscience (2006) [Pubmed]
  28. Exfoliation syndrome angle characteristics: a lack of correlation with amount of disc damage. Cobb, C.J., Blanco, G.C., Spaeth, G.L. The British journal of ophthalmology. (2004) [Pubmed]
  29. Serum gliostatin levels in patients with rheumatoid factor-negative and -positive rheumatoid arthritis and changes of these levels after surgical treatments. Muro, H., Waguri-Nagaya, Y., Otsuka, T., Matsui, N., Asai, K., Kato, T. Clin. Rheumatol. (2001) [Pubmed]
  30. Gliostatin/platelet-derived endothelial cell growth factor as a clinical marker of rheumatoid arthritis and its regulation in fibroblast-like synoviocytes. Waguri, Y., Otsuka, T., Sugimura, I., Matsui, N., Asai, K., Moriyama, A., Kato, T. Br. J. Rheumatol. (1997) [Pubmed]
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