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GLS2  -  glutaminase 2 (liver, mitochondrial)

Homo sapiens

Synonyms: GA, GLS, Glutaminase liver isoform, mitochondrial, L-glutaminase, L-glutamine amidohydrolase, ...
 
 
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Disease relevance of GLS2

 

Psychiatry related information on GLS2

  • L-2-hydroxyglutaric acid (LGA) is the biochemical hallmark of L-2-hydroxyglutaric aciduria (L-OHGA), an inherited neurometabolic disorder characterized by progressive neurodegeneration with cerebellar and pyramidal signs, mental deterioration, epilepsy, and subcortical leukoencephalopathy [4].
  • CONCLUSIONS: These results suggest that prenatal physical activity may decrease risk of LGA, as might be expected given its salutary effects on glucose tolerance [5].
 

High impact information on GLS2

  • Amino acid depletion by enzymes such as L-asparaginase or L-glutaminase has become a popular modality for treatment of human leukemias [6].
  • LGA has long been believed to be present only in liver mitochondria from adult animals [7].
  • A gluconeogenic strain of renal epithelial cells (LLC-PK1-F+) was used to characterize the effect of pH and bicarbonate concentration on the levels of phosphoenolpyruvate carboxykinase (PCK) and glutaminase (GA) mRNAs [8].
  • CONCLUSIONS: Children born LGA of mothers without confirmed impaired glucose tolerance during pregnancy show higher insulin concentrations than AGAs [9].
  • RESULTS: At the time of the assessment, body weight, height, skinfold thickness, BMI, waist circumference, and blood pressure did not differ between the LGA and AGA groups with the exception of head circumference (P < 0.01) [9].
 

Chemical compound and disease context of GLS2

  • The changes for total body fat and lean body mass as a percent of body weight were greatest (P <.001) in LGA infants whose mothers had impaired glucose tolerance [10].
  • Stuart's, Amies' and four thioglycollate/hemin-based media containing, respectively, selenium dioxide and albumin (SA); selenium dioxide, L-glutamine and albumin (SGA); selenium dioxide and L-glutamine (SG); and L-glutamine and albumin (GA); were evaluated as transport media for Haemophilus ducreyi in a simulated, laboratory-based study [11].
  • After collecting cord blood from 156 term neonates (82 males, 74 females; 132 AGA and 22 LGA), we measured the cord levels of leptin, insulin and IGF-I to determine the relationships between these three hormones and relationships of these hormones with birth size (birth weight and ponderal index for adiposity in newborn) and gender [12].
 

Biological context of GLS2

  • LGA genomic sequences were isolated using the genome walking technique [13].
  • Analysis and comparison of these sequences with two LGA cDNA clones and the Human Genome Project database, allowed the determination of the genomic organization of the LGA gene [13].
  • 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 [14].
  • All of the mRNAs that encode the latter proteins contain an AU sequence that is homologous to the pH response element found in GA mRNA [15].
  • Temporal studies identified proteins that were induced either with rapid kinetics similar to PEPCK or with more gradual profiles similar to GA and GDH [15].
 

Anatomical context of GLS2

 

Associations of GLS2 with chemical compounds

  • 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 [18].
  • SPINDLY (SPY) encodes an O-linked N-acetylglucosamine transferase that is considered to be a negative regulator of gibberellin (GA) signaling through an unknown mechanism [19].
  • The LGA group had significantly higher HDL cholesterol levels (P < 0.01), fasting insulin levels (P < 0.01), and HOMA-IR index (P < 0.01) but lower values of the glucose-to-insulin ratio (P < 0.01) as compared with the AGA group [9].
  • The data indicate that LGA provokes oxidation of lipids and proteins and reduces the brain capacity to modulate efficiently the damage associated with an enhanced production of free radicals, possibly by inducing generation of superoxide and hydroxyl radicals, which are trapped by the scavengers used [4].
  • METHODS: The technique of GLS involves iontophoresis of methylene blue dye (1%) at the limbus to focally dye the sclera and to provide subsequent delivery of 10-microsecond pulsed laser energy to the dyed area through a goniolens [20].
 

Other interactions of GLS2

  • Electrophoretic mobility-shift assays confirmed the importance of CAAT- and TATA-like boxes to enhance basal transcription, and demonstrated that HNF-1 motif is a significant distal element for transcriptional regulation of the hLGA gene [13].
  • Progressive deletion analysis of LGA promoter-luciferase constructs indicated that the core promoter is located between nt -141 and +410, with several potential regulatory elements: CAAT, GC, TATA-like, Ras-responsive element binding protein and specificity protein 1 (Sp1) sites [13].
  • The hGA cDNA encodes a 73,427-Da protein that contains an N-terminal mitochondrial targeting signal and retains the primary proteolytic cleavage site characterized for the cytosolic precursor of the rat renal mitochondrial glutaminase [18].
  • Asparaginase derived from vibrio succinogenes, which is virtually free of L-glutaminase activity, was equally inhibitory to MIA PaCa-2 cell growth but did not affect protein synthesis [21].
 

Analytical, diagnostic and therapeutic context of GLS2

  • Furthermore, subcellular fractionation and Western blot analysis revealed that brain LGA was enriched in nuclei where it was catalytically active [7].
  • We now describe the expression of LGA mRNA in the brain of other mammals (cow, mouse, rabbit, and rat) and in different areas of human brain as assessed by Northern blot analysis [7].
  • PURPOSE: The purpose of this study is to evaluate the safety and efficacy of gonioscopic ab interno laser sclerostomy (GLS) in patients with glaucoma [20].
  • This study examined the relationship between measured and derived anthropometric measurements with dual-energy X-ray absorptiometry measured lean and fat mass at 3.0 +/- 2.8 (SD) days in 120 neonates with birth weights appropriate (AGA; n=74), large (LGA; n=30); or small (SGA, n=16) for gestational age [22].
  • Relative placental weight was comparable in the LGA-diabetic cases and in the control groups, but was significantly higher in the AGA-diabetic subgroup [23].

References

  1. Mechanisms governing the expression of the enzymes of glutamine metabolism--glutaminase and glutamine synthetase. Labow, B.I., Souba, W.W., Abcouwer, S.F. J. Nutr. (2001) [Pubmed]
  2. 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]
  3. 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]
  4. Induction of oxidative stress by L-2-hydroxyglutaric acid in rat brain. Latini, A., Scussiato, K., Rosa, R.B., Leipnitz, G., Llesuy, S., Belló-Klein, A., Dutra-Filho, C.S., Wajner, M. J. Neurosci. Res. (2003) [Pubmed]
  5. Maternal physical activity in pregnancy and infant size for gestational age. Alderman, B.W., Zhao, H., Holt, V.L., Watts, D.H., Beresford, S.A. Annals of epidemiology. (1998) [Pubmed]
  6. Tumoricidal potential of nutritional manipulations. Demetrakopoulos, G.E., Brennan, M.F. Cancer Res. (1982) [Pubmed]
  7. Nuclear localization of L-type glutaminase in mammalian brain. Olalla, L., Gutiérrez, A., Campos, J.A., Khan, Z.U., Alonso, F.J., Segura, J.A., Márquez, J., Aledo, J.C. J. Biol. Chem. (2002) [Pubmed]
  8. 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]
  9. Lipid profile, glucose homeostasis, blood pressure, and obesity-anthropometric markers in macrosomic offspring of nondiabetic mothers. Evagelidou, E.N., Kiortsis, D.N., Bairaktari, E.T., Giapros, V.I., Cholevas, V.K., Tzallas, C.S., Andronikou, S.K. Diabetes Care (2006) [Pubmed]
  10. Disproportionate alterations in body composition of large for gestational age neonates. Hammami, M., Walters, J.C., Hockman, E.M., Koo, W.W. J. Pediatr. (2001) [Pubmed]
  11. Transport media for Haemophilus ducreyi. Dangor, Y., Radebe, F., Ballard, R.C. Sexually transmitted diseases. (1993) [Pubmed]
  12. The relationship of the levels of leptin, insulin-like growth factor-I and insulin in cord blood with birth size, ponderal index, and gender difference. Yang, S.W., Kim, S.Y. Journal of pediatric endocrinology & metabolism : JPEM. (2000) [Pubmed]
  13. Genomic organization and transcriptional analysis of the human l-glutaminase gene. Pérez-Gómez, C., Matés, J.M., Gómez-Fabre, P.M., del Castillo-Olivares, A., Alonso, F.J., Márquez, J. Biochem. J. (2003) [Pubmed]
  14. 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]
  15. Proteomic analysis of the adaptive response of rat renal proximal tubules to metabolic acidosis. Curthoys, N.P., Taylor, L., Hoffert, J.D., Knepper, M.A. Am. J. Physiol. Renal Physiol. (2007) [Pubmed]
  16. Phosphate-dependent glutaminase of rat skeletal muscle. Some properties and possible role in glutamine metabolism. Swierczyński, J., Bereznowski, Z., Makarewicz, W. Biochim. Biophys. Acta (1993) [Pubmed]
  17. Elevated umbilical cord ghrelin concentrations in small for gestational age neonates. Farquhar, J., Heiman, M., Wong, A.C., Wach, R., Chessex, P., Chanoine, J.P. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  18. 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]
  19. The rice SPINDLY gene functions as a negative regulator of gibberellin signaling by controlling the suppressive function of the DELLA protein, SLR1, and modulating brassinosteroid synthesis. Shimada, A., Ueguchi-Tanaka, M., Sakamoto, T., Fujioka, S., Takatsuto, S., Yoshida, S., Sazuka, T., Ashikari, M., Matsuoka, M. Plant J. (2006) [Pubmed]
  20. Gonioscopic ab interno laser sclerostomy. A pilot study in glaucoma patients. Latina, M.A., Melamed, S., March, W.F., Kass, M.A., Kolker, A.E. Ophthalmology (1992) [Pubmed]
  21. Mechanism of sensitivity of cultured pancreatic carcinoma to asparaginase. Wu, M.C., Arimura, G.K., Yunis, A.A. Int. J. Cancer (1978) [Pubmed]
  22. Body composition in neonates: relationship between measured and derived anthropometry with dual-energy X-ray absorptiometry measurements. Koo, W.W., Walters, J.C., Hockman, E.M. Pediatr. Res. (2004) [Pubmed]
  23. Placental pathology in women with type 1 diabetes and in a control group with normal and large-for-gestational-age infants. Evers, I.M., Nikkels, P.G., Sikkema, J.M., Visser, G.H. Placenta (2003) [Pubmed]
 
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