Alterations in glutamine synthetase activity in rat skeletal muscle are associated with advanced age

Nutrition ◽  
2006 ◽  
Vol 22 (7-8) ◽  
pp. 778-785 ◽  
Author(s):  
Carole Pinel ◽  
Véronique Coxam ◽  
Michelle Mignon ◽  
Daniel Taillandier ◽  
Christine Cubizolles ◽  
...  
1987 ◽  
Vol 252 (1) ◽  
pp. E49-E56
Author(s):  
J. E. Albina ◽  
W. Henry ◽  
P. A. King ◽  
J. Shearer ◽  
B. Mastrofrancesco ◽  
...  

Wounding with lambda-carrageenan results in a marked decrease in the intracellular-free glutamine content of rat skeletal muscle. The potential mechanisms for this finding, including alterations in glutamine release, glutamine utilization, and glutamine synthesis, were investigated in rats under pentobarbital anesthesia. Wounding did not increase glutamine release from muscle during incubation or isolated hindlimb perfusion. Wounded muscle utilized more glutamine than nonwounded muscle, as measured both by the production of [14C]O2 and of -glutamate from labeled glutamine. Maximal glutamine synthetase activity was increased by wounding. The increase in glutamine synthetase activity in wounded muscle was prevented by adrenalectomy and restored by replacement doses of corticosterone in wounded adrenalectomized animals. The decrease in muscle free glutamine induced by wounding is therefore not mediated by an increase in the release of this amino acid, nor by a reduction in the tissue capacity for glutamine synthesis, but by an increase in glutamine utilization at the site of injury. This difference is apparently determined by the utilization of glutamine by the cellular components of the inflammatory infiltrate, which were shown to be capable of active glutaminolysis.


1989 ◽  
Vol 257 (6) ◽  
pp. E885-E894 ◽  
Author(s):  
T. B. Kelso ◽  
C. R. Shear ◽  
S. R. Max

Glutamine synthesis and utilization were studied in the plantaris muscle after removal of its functional synergists, the soleus and gastrocnemius muscles. Rat plantaris muscle was compared with unoperated controls at 7, 14, and 30 days after synergist ablation and induction of hypertrophy. Glutamine synthetase activity increased from 6.17 +/- 1.77 to 33.92 +/- 2.23 nmol.h-1.mg protein-1, and glutaminase activities increased from 98.63 +/- 23.05 to 478.70 +/- 64.17 nmol.h-1.mg protein-1 7 days after surgery and remained elevated at 14 and 30 days. Sham-operated controls examined 7 days after surgery did not exhibit significantly increased glutamine synthetase activity. Histological examination revealed a large proliferation of connective tissue cells, as well as cells involved in tissue repair and inflammation; this influx was maximal 1 wk after surgery. The activity of the oxidative enzymes of the pentose phosphate pathway increased from 3.08 +/- 4.31 to 20.86 +/- 1.13 nmol.min-1.mg protein-1 1 wk after surgery. The time course of changes in pentose phosphate pathway enzymes was similar to that of the increases in glutamine synthetase, glutaminase, and cellular infiltration. Increases in muscle wet weight followed a different time course than changes in glutamine synthetase, glutaminase, and pentose phosphate pathway activities. It is concluded that the initial increases in plantaris muscle weight are probably due to edema, connective tissue proliferation, and cells involved in tissue repair and inflammation. The increase in glutamine synthetase activity appears to occur in skeletal muscle, whereas the changes in glutaminase and pentose phosphate pathway activities appear to represent infiltrating inflammatory cells. Furthermore, the increase in glutamine synthetase activity may serve to support the infiltrating cells, which appear to lack substantial capacity for glutamine production. These results represent a functional relationship between skeletal muscle glutamine synthesis and utilization by cells mediating inflammation and connective tissue repair and synthesis.


1990 ◽  
Vol 259 (2) ◽  
pp. E148-E154 ◽  
Author(s):  
H. S. Hundal ◽  
P. Babij ◽  
P. W. Watt ◽  
M. R. Ward ◽  
M. J. Rennie

Rat skeletal muscle glutamine fell by 40% from 4.18 to 2.5 mumols/g wet weight (P less than 0.01) after 4 days of denervation. Over the same period net glutamine efflux from denervated hindlimbs [i.e., arteriovenous (a-v) concentration differences x blood flow] increased 3.5-fold (from -6.72 +/- 1.73 to -26 +/- 4.81 nmol.min-1.g-1, P less than 0.001). Gastrocnemius glutamine synthetase activity fell 48% after denervation (from 475 +/- 81 to 248 +/- 39 nmol.min-1.g-1, P less than 0.001), but glutaminase activity was not significantly altered (17 nmol.min-1.g-1). The maximal activity (Vmax) of the unidirectional Na(+)-dependent glutamine transporter (system Nm) was depressed by 45% from 1,020 +/- 104 to 571 +/- 9 nmol.min-1.g-1 (P less than 0.01), but the concentration at which transport was half maximal (Km) was not significantly altered (control 8.1 +/- 0.6 mM; denervated 6.52 +/- 0.12). Hindlimb denervation resulted in an increase of intramuscular Na+ by 17% and a fall of K+ by 12%, and the resting membrane potential in isolated muscles decreased from -75 +/- 10 to -59.5 +/- 5.5 mV. Membrane potential of perfused denervated muscle, isolated after acute addition of the Na+ channel blocker tetrodotoxin (TTX, 3 microM), repolarized to -66.4 +/- 3.2 mV. In perfused denervated preparations TTX caused an acute recovery of Vmax of unidirectional glutamine transport to 848 +/- 75 nmol.min-1.g-1; Km was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)


1983 ◽  
Vol 216 (2) ◽  
pp. 523-525 ◽  
Author(s):  
P A King ◽  
L Goldstein ◽  
E A Newsholme

Metabolic acidosis stimulates the rate of glutamine release from muscle, and this in turn is used by the kidney in acid-base balance. NH4Cl, HCl or diabetic ketoacidosis increases the maximum activity of glutamine synthetase in skeletal muscle. Starvation and administration of adrenal steroids also increase the activity of the enzyme in muscle.


1983 ◽  
Vol 101 (2) ◽  
pp. 265-273 ◽  
Author(s):  
Jennifer M. Pell ◽  
Julia Tooley ◽  
Marjorie K. Jeacock ◽  
D. A. L. Shepherd

SUMMARYThe activities of glutamine synthetase, phosphate-dependent glutaminase, phosphate-independent glutaminase, glutamate dehydrogenase, γ-glutamyl transferase and glutamine-oxo-acid aminotransferase were assayed in liver, kidney cortex, brain (cerebral hemispheres), spleen, skeletal muscle and ileum obtained from lambs of 100–260 days conceptual age. A curve was fitted to each set of data relating enzyme activity and conceptual age.In the ileum, glutaminase and γ-glutamyl transferase activities declined during development. Glutamine synthetase activity in the spleen increased markedly after birth, whereas glutamate dehydrogenase activity declined as rumen function was established. In the liver, glutamate dehydrogenase and glutamine synthetase activities were highest in suckling lambs and there was a gradual increase in hepatic γ-glutamyl transferase activity throughout the period studied. The activity of phosphate-dependent glutaminase was lowest in the kidney cortex of ruminating lambs but renal activities of glutamate dehydrogenase, phosphate-independent glutaminase, glutamine synthetase and γ-glutamyl transferase were highest in ruminating lambs. In skeletal muscle, a gradual increase in glutamine synthetase activity occurred after 180 days conceptual age, whereas there was no detectable glutaminase activity in ruminating lambs. In the brain, there was an increase in glutamate dehydrogenase, phosphatedependent glutaminase and glutamine synthetase activities during the foetal and early suckling periods, whereas γ-glutamyl transferase activity increased throughout the period studied.Glutamine-oxo-acid aminotransferase activity was not detected in any of the tissues studied. Phosphate-independent glutaminase activity was always less than 10% of phosphate-dependent glutaminase activity and therefore must have a minor role in the metabolism of glutamine in lambs.A consideration of the relative activities of the enzymes at different stages of development indicated that the ileum, spleen, liver, kidney cortex and brain have a substantial potential for glutamine utilization during foetal life. As a lamb matures after birth, there are changes in the metabolism of glutamate and glutamine which indicate that there is a greater potential for net glutamine synthesis in older lambs. This could be associated with the need for detoxification of ammonia in ruminating lambs.


1970 ◽  
Vol 119 (2) ◽  
pp. 145-156 ◽  
Author(s):  
Khalid Iqbal ◽  
J. H. Ottaway

1. Glutamine synthetase activity has been determined in extracts of rat cardiac and skeletal muscle and kidney, after treatment to ensure that the rate of synthesis was proportional to time of incubation and to amount of extract added. The activity was measured by two methods, with hydroxylamine as substrate. 2. No activity was detected in rat heart extract by either method. The activity in skeletal muscle was of the order of 20μmol of glutamylhydroxamate synthesized/h per g of tissue under optimum conditions. The activity in kidney extracts was 180μmol/h per g of tissue when measured as ferric hydroxamate. 3. The activity in both skeletal-muscle and kidney extracts was inhibited by Pi. The inhibition is competitive for the muscle enzyme, with a Ki of 12mm. For the kidney enzyme the inhibition is non-competitive, and less marked. Possible enzyme mechanisms that would lead to these types of inhibition are discussed. 4. Several observations are reported that suggest that the enzymes from muscle and kidney are not identical. 5. Growth hormone, either in vivo or in vitro, did not affect the measured glutamine synthetase activity of tissue extracts.


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