scholarly journals Inactivation In vivo of Glutamine Synthetase and NAD-specific Glutamate Dehydrogenase: Its Role in the Regulation of Glutamine Synthesis in Yeasts

1971 ◽  
Vol 69 (3) ◽  
pp. 423-427 ◽  
Author(s):  
A. R. FERGUSON ◽  
A. P. SIMS
Keyword(s):  
Glutamine Synthetase ◽  
Glutamate Dehydrogenase ◽  
Glutamine Synthesis

scholarly journals Do sex steroids regulate glutamine synthesis with age?

2002 ◽  
Vol 282 (1) ◽  
pp. E215-E221 ◽  
Author(s):  
Lionel Verdier ◽  
Yves Boirie ◽  
Sebastien Van Drieesche ◽  
Michelle Mignon ◽  
Rene-Jean Begue ◽  
...  
Keyword(s):  
Glutamine Synthetase ◽  
Sex Steroids ◽  
Tibialis Anterior Muscle ◽  
Female Rats ◽  
Female Wistar Rats ◽  
Endocrine Status ◽  
Key Enzyme ◽  
Reproductive Endocrine ◽  
Glutamine Synthesis

Glutamine synthetase, a key enzyme in the production of glutamine, is known to be induced by glucocorticoids and preserved in skeletal muscle during aging, but the effect of other steroids, such as sex steroids (progesterone, estradiol), is unknown in vivo. The aim of this study was to determine whether progesterone or estradiol plays a role in the regulation of glutamine synthetase (GS) with aging. The effects of glucocorticoids and sex steroids on muscle GS activity and mRNA expression were measured in adult (6–8 mo; n = 7 in each group) and aged (26 mo; n= 10 in each group) female Wistar rats after adrenalectomy (ADX), ovariectomy (OV), or both (ADXOV) and were compared with those in sham-operated (Sham) control rats. In tibialis anterior muscle, ADX noticeably decreased both GS activity and expression irrespective of age (50–60%; P < 0.05), whereas OV had no effect at either age. Progesterone and estradiol replacement had no effect on the recovery of muscle GS response in either ADX or OV rats, regardless of age. In contrast, heart GS activity was decreased by ADX in aged animals only. These results suggest that the reproductive endocrine status of female rats does not affect muscle GS activity either in muscle or in heart, in young or aged animals, and that the heart GS response to steroids may be differently regulated in aged rats.

scholarly journals The Effect of Bialaphos on Ammonium-Assimilation and Photosynthesis I. Effect on the Enzymes of Ammonium-Assimilation

1989 ◽  
Vol 44 (1-2) ◽  
pp. 97-102 ◽  
Author(s):  
Aloysius Wild ◽  
Christine Ziegler
Keyword(s):  
Glutamine Synthetase ◽  
Glutamate Dehydrogenase ◽  
Ammonium Assimilation ◽  
Inhibiting Effect ◽  
Whole Plants ◽  
Leaf Homogenate

Abstract In this investigation, the effect of bialaphos (phosphinothricyl-alanyl-alanine) on the enzymes involved in NH4+-assimilation - glutamine synthetase, glutamine-2-oxoglutarate aminotransferase, glutamate dehydrogenase - is examined and compared to the effect of phosphinothricin (glufosinate) on the same enzymes. Bialaphos was given to whole plants (in vivo) and to leaf homogenate (in vitro). The investigation showed that bialaphos has an inhibiting effect on glutamine synthetase in vivo, but not in vitro. In contrast to this, phosphinothricin inhibits glutamine synthetase in vitro as well as in vivo. It was found that bialaphos, similar to phosphinothricin, does not inhibit glutamine-2-oxoglutarate aminotransferase and glutamate dehydrogenase in vivo or in vitro. Only at bialaphos concentrations exceeding 10 mM, there is an inhibition of glutamate dehydrogenase in vitro. Using radioactive [3H]bialaphos (phosphinothricyl-3H-alanyl-alanine) it could be demonstrated that in the plant, bialaphos is split into phosphinothricin and alanine. The phosphinothricin released is probably the active herbicide component. Consequently, the herbicidal effects of phosphinothricin and bialaphos are the same.

The green hydra symbiosis and ammonium. I. The role of the host in ammonium assimilation and its possible regulatory significance

1986 ◽  
Vol 229 (1256) ◽  
pp. 299-314 ◽  
Keyword(s):  
Glutamine Synthetase ◽  
Glutamate Dehydrogenase ◽  
Ammonium Assimilation ◽  
Nitrogen Status ◽  
Continuous Darkness ◽  
Methionine Sulphoximine ◽  
Vacuolar Ph ◽  
Regulatory Significance

Evidence for ammonium assimilation by host and symbiont in algal─invertebrate symbioses is summarized and critically evaluated. The host from all strains of hydra studied possessed glutamine synthetase (GS) and glutamate dehydrogenase (GDH) activities. The host from associations with high maltose releasing algae (E/E, E /3N8) had high GS and low GDH activities, whereas aposymbiotic animals (EALB) and the association with a low maltose releasing alga (E/NC) had low GS and high GDH activities. The observation that symbiotic animals do not release ammonium in the light, whereas aposymbiotic animals release substantial amounts, may be explicable on the basis of variation in the ability of the host to assimilate ammonium. Thus, the photosynthetic inhibitor DCMU had no effect on ammonium release by symbiotic animals, with the possible exception of E/NC. Methionine sulphoximine (MSO) completely inhibited GS activity from EALB both in vitro and in vivo . In the presence of MSO, ammonium release was enhanced in both EALB and E/E. In continuous darkness, an increase in ammonium released by symbiotic animals (E/E) was correlated with a decrease in host GS activity. It is suggested that the evidence is consistent with host and not symbiont assimilation of ammonium. A model of symbiont regulation is proposed based on regulation of ammonium supply as a means of controlling both perialgal vacuolar pH and symbiont nitrogen status.

scholarly journals A 1H/15N n.m.r. study of nitrogen metabolism in cultured mammalian cells

1993 ◽  
Vol 291 (2) ◽  
pp. 485-492 ◽  
Author(s):  
J C Street ◽  
A M Delort ◽  
P S H Braddock ◽  
K M Brindle
Keyword(s):  
Glutamine Synthetase ◽  
Glutamate Dehydrogenase ◽  
Cell Lines ◽  
Mammalian Cells ◽  
Cho Cell ◽  
15N Labelling ◽  
Hela Cell Lines ◽  
Proton Resonances ◽  
In Cells

1. Heteronuclear 1H/15N n.m.r. experiments are described in which 15N labelling of cellular metabolites is detected via their proton resonances. 2. These n.m.r. experiments have been used to monitor label redistribution amongst extracellular metabolites in cultures of mammalian cells incubated with L-[2-15N]glutamine, L-[5-15N]glutamine and 15NH4Cl. Label redistribution was monitored in two HeLa cell lines and in two CHO cell lines which showed a range of extractable activities of glutamate dehydrogenase, glutaminase and glutamine synthetase. 3. In cells incubated with L-[2-15N]glutamine the 15N label was subsequently found in a number of metabolites including alanine, aspartate, glycine and pyrrolidone-5-carboxylic acid. There was no detectable production of 15NH4+, showing that most of the glutamate formed in the reaction catalysed by glutaminase was subsequently transaminated rather than oxidatively deaminated by glutamate dehydrogenase. 4. Incubation of cells with L-[5-15N]glutamine showed that the ammonia in the cultures was derived predominantly from the amide group of glutamine. 5. The rate of formation of L-[5-15N]glutamine in cells incubated with 15NH4Cl was used to estimate glutamine synthetase flux in vivo. Flux in this reaction was only observable in the two CHO cell lines which express relatively high levels of the enzyme.

scholarly journals Control of glutamine synthesis in rat liver

1971 ◽  
Vol 124 (3) ◽  
pp. 653-660 ◽  
Author(s):  
P Lund
Keyword(s):  
Glutamine Synthetase ◽  
De Novo ◽  
Synthetic Medium ◽  
Linear Rate ◽  
Rapid Release ◽  
Initial Release ◽  
Glutamine Synthesis ◽  
Glutamine Production

1. On perfusion of livers from fed rats with a semi-synthetic medium containing no added amino acids there is a rapid release of glutamine during the first 15min (15.6±0.8μmol/h per g wet wt.; mean±s.e.m. of 35 experiments), followed by a low linear rate of production (3.6±0.3μmol/h per g wet wt.; mean±s.e.m. of three experiments). The rapid initial release can be accounted for as wash-out of preexisting intracellular glutamine. 2. Addition of readily permeating substrates, or substrate combinations, giving rise to intracellular glutamate or ammonia, or both, did not appreciably increase the rate of glutamine production over the endogenous rate. The maximum rate obtained was from proline plus alanine; even then the rate represented less than one-fortieth of the capacity of glutamine synthetase measured in vitro. 3. Complete inhibition of respiration in the perfusions [no erythrocytes in the medium; 1mm-cyanide; N2%CO2 (95:5) in the gas phase] or perfusion with glutamine synthetase inhibitors [l-methionine dl-sulphoximine; dl-(%)-allo-δ-hydroxylysine] abolishes the low linear rate of glutamine synthesis, but not the initial rapid release of glutamine. 4. In livers from 48h-starved rats initial release (0–15min) of glutamine was decreased (10.6±1.1μmol/h per g wet wt.; mean±s.e.m. of 11 experiments) and the subsequent rate of glutamine production was lower than in livers from fed rats. Again proline plus alanine was the only substrate combination giving an increase significantly above the endogenous rate. 5. The rate of glutamine synthesis de novo by the liver is apparently unrelated to the tissue content of glutamate or ammonia. 6. The blood glutamine concentration is increased by 50% within 1h of elimination of the liver from the circulation of rats in vivo. 7. There is an output of glutamine by the brain under normal conditions; the mean arterio-venous difference for six rats was 0.023μmol/ml. 8. The high potential activity of liver glutamine synthetase appears to be inhibited by some unknown mechanism: the function of the liver under normal conditions is probably the disposal of glutamine produced by extrahepatic tissues.

Glutamate and glutamine metabolism in the ovine placenta

1983 ◽  
Vol 101 (2) ◽  
pp. 275-281 ◽  
Author(s):  
Jennifer M. Pell ◽  
Marjorie K. Jeacock ◽  
D. A. L. Shepherd
Keyword(s):  
Glutamine Synthetase ◽  
Glutamate Dehydrogenase ◽  
Placental Transfer ◽  
Umbilical Vein ◽  
Maternal Blood ◽  
Glutamine Metabolism ◽  
Arterial Blood ◽  
Foetal Circulation ◽  
Glutamine Synthesis ◽  
Glutamyl Transferase

SUMMARYThe concentration of glutamate and of glutamine was measured in whole blood obtained from a maternal artery, a uterine vein, a foetal artery and an umbilical vein of chronically catherized ewes and foetuses from 100 to 140 days after conception. The activities of glutamate dehydrogenase, phosphate-dependent glutaminase, phosphateindependent glutaminase, glutamine synthetase, γ-glutamyl transferase and glutamine-oxo-acid aminotransferase were measured in placentomes obtained from ewes during a similar period of gestation.The concentrations of glutamate in blood from maternal vessels remained constant, whereas there was a significant decline (P < 0·001) in the concentration of glutamate in foetal blood. Glutamine concentrations declined significantly (P < 0·05) in maternal blood and in foetal arterial blood (P < 0·001), whereas the concentration of glutamine in umbilical venous blood remained constant.Mean arterio-venous differences for glutamate indicated that there was no net uptake from or release into maternal blood by the uterus. However, there was a significant (P < 0·02) uptake of glutamate by the placenta from the foetal circulation. Glutamine release from the placenta into the foetal circulation increased as the foetus matured.Significant activities of glutamate dehydrogenase, γ-glutamyl transferase, glutamine synthetase and phosphate-dependent glutaminase were found in the placenta but there was no significant relationship between the activities of these enzymes and the gestational age of the foetus. The enzyme profile indicated that the placenta has a substantial potential for net glutamine synthesis.It is concluded that, for a 140-day foetus, the release of glutamine from the placenta accounts for more than half of its nitrogen requirement. Direct placental transfer of glutamine from maternal blood accounts for only one-third of the glutamine released by the placenta into the foetal circulation of a 140-day foetus. Therefore, the remainder of the glutamine is synthesized in the placenta from glutamate. Only one-third of the glutamate required for this placental glutamine synthesis is from the glutamate released by the foetus. The remainder must be derived either from 2-oxoglutarate, as the result of aminotransferase or glutamate dehydrogenase activities, or from glutathione by the action of γ-glutamyl transferase.

scholarly journals Protection Elicited by Two Glutamine Auxotrophs of Mycobacterium tuberculosis and In Vivo Growth Phenotypes of the Four Unique Glutamine Synthetase Mutants in a Murine Model

2006 ◽  
Vol 74 (11) ◽  
pp. 6491-6495 ◽  
Author(s):  
Sunhee Lee ◽  
Bo-Young Jeon ◽  
Svetoslav Bardarov ◽  
Mei Chen ◽  
Sheldon L. Morris ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Glutamine Synthetase ◽  
Mycobacterium Bovis ◽  
Murine Model ◽  
Triple Mutant ◽  
Auxotrophic Mutants ◽  
Bcg Vaccination ◽  
In Vivo Growth ◽  
Subcutaneous Immunization

ABSTRACT We generated four individual glutamine synthetase (GS) mutants (ΔglnA1, ΔglnA2, ΔglnA3, and ΔglnA4) and one triple mutant (ΔglnA1EA2) of Mycobacterium tuberculosis to investigate the roles of GS enzymes. Subcutaneous immunization with the ΔglnA1EA2 and ΔglnA1 glutamine auxotrophic mutants conferred protection on C57BL/6 mice against an aerosol challenge with virulent M. tuberculosis, which was comparable to that provided by Mycobacterium bovis BCG vaccination.

Regulation of glutamine-repressible gene products by the GLN3 function in Saccharomyces cerevisiae

1984 ◽  
Vol 4 (12) ◽  
pp. 2758-2766
Author(s):  
A P Mitchell ◽  
B Magasanik
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Glutamine Synthetase ◽  
Glutamate Dehydrogenase ◽  
Opposite Effect ◽  
Nuclear Gene ◽  
Yeast Saccharomyces Cerevisiae ◽  
Two Dimensional Gel Electrophoresis ◽  
Regulatory Circuit ◽  
Glutamate Dehydrogenase Activity ◽  
Glutamine Limitation

Mutants of the yeast Saccharomyces cerevisiae have been isolated which fail to derepress glutamine synthetase upon glutamine limitation. The mutations define a single nuclear gene, GLN3, which is located on chromosome 5 near HOM3 and HIS1 and is unlinked to the structural gene for glutamine synthetase, GLN1. The three gln3 mutations are recessive, and one is amber suppressible, indicating that the GLN3 product is a positive regulator of glutamine synthetase expression. Four polypeptides, in addition to the glutamine synthetase subunit are synthesized at elevated rates when GLN3+ cultures are shifted from glutamine to glutamate media as determined by pulse-labeling and one- and two-dimensional gel electrophoresis. The response of all four proteins is blocked by gln3 mutations. In addition, the elevated NAD-dependent glutamate dehydrogenase activity normally found in glutamate-grown cells is not found in gln3 mutants. Glutamine limitation of gln1 structural mutants has the opposite effect, causing elevated levels of NAD-dependent glutamate dehydrogenase even in the presence of ammonia. We suggest that there is a regulatory circuit that responds to glutamine availability through the GLN3 product.

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