The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Gene Review

GLS  -  glutaminase

Sus scrofa

Synonyms: GA, PAG
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of GLS


High impact information on GLS

  • Desenzitation to inhibition by mersalyl and N-ethylmaleimide occurred when the assay was performed under optimal conditions for phosphate activated glutaminase (i.e. in the presence of 150 mM phosphate, 20 mM glutamine and at pH 8.6) [3].
  • Phosphate-activated glutaminase in intact pig renal mitochondria was inhibited 50-70% by the sulfhydryl reagents mersalyl and N-ethylmaleimide (0.3-1.0 mM), when assayed at pH 7.4 in the presence of no or low phosphate (10 mM) and glutamine (2 mM) [3].
  • The results suggest that phosphate-activated glutaminase has a functionally predominant external localization in the inner mitochondrial membrane [3].
  • Furthermore, both calcium (which activates glutamine hydrolysis), as well as alanine (which has no effect on the hydrolytic rate), inhibited glutamine transport into the mitochondria, indicating that transport of glutamine is not rate-limiting for the glutaminase reaction [3].
  • Exposure of cells to either PGF2 alpha or TPA completely inhibited the low pH-induced increases in (15N)ammonia formation from incubations with 5-15N, reflecting reduced flux through the mitochondrial phosphate-dependent glutaminase, and from (2-15N)glutamine, reflecting reduced flux through the mitochondrial glutamate dehydrogenase pathway [4].

Chemical compound and disease context of GLS

  • Pulse-chase studies with 14C-glutamine as well as studies with various metabolic inhibitors of the ammoniagenic pathways suggest that glutamine in LLC-PK1 cells is metabolized via mitochondrial pathway and that intramitochondrial phosphate-dependent glutaminase pathway plays a predominant role in the regulation of ammoniagenesis to acute acidosis [5].
  • Thus reduced cellular glutamate appears to coordinate activation of intracellular glutaminase to the apical membrane exchanger, consistent with the functioning kidney response to metabolic acidosis [6].

Biological context of GLS

  • However, insertion of short segments of GA mRNA containing the direct repeat or a single eight-base AU sequence was sufficient to impart a fivefold pH-responsive stabilization to the chimeric mRNA [7].
  • It is concluded that aspartate aminotransferase activity appears to be especially concerned with cochlear energy metabolism, while glutaminase activity may function in transmitter metabolism in the guinea pig cochlea [8].
  • Although GA activation occurs as the result of the fall in cellular L-glutamate, PP did not increase; in fact, it slightly decreased as evidenced by an increased electrical resistance (from 180 +/- 12 to 210 +/- 10 omega x cm2, P < 0.02) and reduction in L-[(14)C]glucose permeability (2.72 +/- 0.75 to 2.28 +/- 0.37%, P = 0.10) [9].

Anatomical context of GLS

  • Two pools of phosphate-activated glutaminase (PAG) were separated from pig and rat renal mitochondria [10].
  • Thus the enzymatically active PAG is assumed to be localized on the outer face of the inner mitochondrial membrane [10].
  • The activity of this pool of PAG appears to be regulated by compounds in the cytosol, of which glutamate may be most important [10].
  • LLC-PK1-FBPase+ cells, a pH-responsive porcine kidney cell line, express four distinct GA mRNAs [1].
  • Given this complexity, a careful assessment of GA mRNA species, of basal expression, and of growth conditions are essential for a meaningful analysis of GA mRNA levels in cultured cells [11].

Associations of GLS with chemical compounds


Other interactions of GLS


Analytical, diagnostic and therapeutic context of GLS


  1. Complexity and species variation of the kidney-type glutaminase gene. Porter, L.D., Ibrahim, H., Taylor, L., Curthoys, N.P. Physiol. Genomics (2002) [Pubmed]
  2. Limited proteolysis of Pseudomonas glutaminase by porcine trypsin. Abe, T., Takenaka, O., Inada, Y. FEBS Lett. (1975) [Pubmed]
  3. Evidence indicating that pig renal phosphate-activated glutaminase has a functionally predominant external localization in the inner mitochondrial membrane. Kvamme, E., Torgner, I.A., Roberg, B. J. Biol. Chem. (1991) [Pubmed]
  4. Prostaglandin F2 alpha- and 12-O-tetradecanoylphorbol-13-acetate-induced alterations in the pathways of renal ammoniagenesis. Sahai, A., Nissim, I., Sandler, R.S., Tannen, R.L. J. Am. Soc. Nephrol. (1995) [Pubmed]
  5. Response of ammonia metabolism to acute acidosis: insights from cultured renal epithelium. Tannen, R.L., Sahai, A. Am. J. Kidney Dis. (1989) [Pubmed]
  6. Response of LLC-PK1-F+ cells to metabolic acidosis. Mu, X., Welbourne, T. Am. J. Physiol. (1996) [Pubmed]
  7. Specificity and functional analysis of the pH-responsive element within renal glutaminase mRNA. Laterza, O.F., Curthoys, N.P. Am. J. Physiol. Renal Physiol. (2000) [Pubmed]
  8. Quantitative distributions of aspartate aminotransferase and glutaminase activities in the guinea pig cochlea. Wiet, G.J., Godfrey, D.A., Rubio, J.A., Ross, C.D. The Annals of otology, rhinology, and laryngology. (1990) [Pubmed]
  9. Glutamate transport and not cellular content modulates paracellular permeability in LLC-PK1-F+ cells. Welbourne, T.C., Chevalier, D. Am. J. Physiol. (1997) [Pubmed]
  10. Properties and submitochondrial localization of pig and rat renal phosphate-activated glutaminase. Roberg, B., Torgner, I.A., Laake, J., Takumi, Y., Ottersen, O.P., Kvamme, E. Am. J. Physiol., Cell Physiol. (2000) [Pubmed]
  11. Differential expression of multiple glutaminase mRNAs in LLC-PK1-F+ cells. Porter, D., Hansen, W.R., Taylor, L., Curthoys, N.P. Am. J. Physiol. (1995) [Pubmed]
  12. Synthesis of citrulline from glutamine in pig enterocytes. Wu, G., Knabe, D.A., Flynn, N.E. Biochem. J. (1994) [Pubmed]
  13. Regulatory effects of fatty acyl-coenzyme A derivatives on phosphate-activated pig brain and kidney glutaminase in vitro. Kvamme, E., Torgner, I.A. Biochem. J. (1975) [Pubmed]
  14. Effect of lesions of the olfactory bulb on the levels of amino acids and related enzymes in the olfactory cortex of the guinea pig. Sandberg, M., Bradford, H.F., Richards, C.D. J. Neurochem. (1984) [Pubmed]
  15. Tetraphenylboron - a potent activator of kidney mitochondrial glutaminase. Kovaĉević, Z. FEBS Lett. (1976) [Pubmed]
  16. High-affinity glycine and glutamate transport in pig forebrain white and gray matter: A quantitative study. Henjum, S., Hassel, B. Neurochem. Int. (2007) [Pubmed]
  17. Glutamine synthesis in the developing porcine placenta. Self, J.T., Spencer, T.E., Johnson, G.A., Hu, J., Bazer, F.W., Wu, G. Biol. Reprod. (2004) [Pubmed]
  18. Somatotropin-induced amino acid conservation in pigs involves differential regulation of liver and gut urea cycle enzyme activity. Bush, J.A., Wu, G., Suryawan, A., Nguyen, H.V., Davis, T.A. J. Nutr. (2002) [Pubmed]
  19. Effects of L-glutamine, glutaminase and glutamine synthetase on CAP threshold of cochlear nerve of guinea pig. Sun, Y.W. Sci. China, Ser. B, Chem. Life Sci. Earth Sci. (1991) [Pubmed]
WikiGenes - Universities