Metabolic pathways implicated in the kinetic impairment of muscle glutamine homeostasis in adult and old glucocorticoid-treated rats

2004 ◽  
Vol 287 (4) ◽  
pp. E671-E676 ◽  
Author(s):  
R. Minet-Quinard ◽  
C. Moinard ◽  
F. Villie ◽  
M. P. Vasson ◽  
L. Cynober
Keyword(s):  
De Novo ◽  
Muscle Protein ◽  
Glutamine Metabolism ◽  
Control Group ◽  
Synthetase Activity ◽  
Glutamine Synthetase Activity ◽  
Protein Breakdown ◽  
Adult Rats ◽  
Old Rats ◽  
Glutamine Production

An impairment of muscle glutamine metabolism in response to dexamethasone (DEX) occurs with aging. To better characterize this alteration, we have investigated muscle glutamine release with regard to muscle glutamine production (net protein breakdown, de novo glutamine synthesis) in adult and old glucocorticoid-treated rats. Male Sprague-Dawley rats (3 or 24 mo old) were divided into seven groups: three groups received 1.5 mg/kg of DEX once a day by intraperitoneal injection for 3, 5, or 7 days; three groups were pair fed to the three treated groups, respectively; and one control group of healthy rats was fed ad libitum. Muscle glutamine synthetase activity increased earlier in old rats ( day 3) than in adult rats ( day 7), whereas an increase in muscle glutamine release occurred later in old rats ( day 5) than in adult DEX-treated rats ( day 3). Consequently, muscle glutamine concentration decreased later in old rats ( day 5) than in adults ( day 3). Finally, net muscle protein breakdown increased only in old DEX-treated rats ( day 7). In conclusion, the impairment of muscle glutamine metabolism is due to a combination of an increase in glutamine production and a delayed increase in glutamine release.

Growth hormone decreases muscle glutamine production and stimulates protein synthesis in hypercatabolic patients

2000 ◽  
Vol 279 (2) ◽  
pp. E323-E332 ◽  
Author(s):  
Gianni Biolo ◽  
Fulvio Iscra ◽  
Alessandra Bosutti ◽  
Gabriele Toigo ◽  
Beniamino Ciocchi ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Protein Synthesis ◽  
Amino Acid ◽  
De Novo ◽  
Muscle Protein ◽  
Recombinant Human Growth Hormone ◽  
Glutamine Metabolism ◽  
Trauma Patients ◽  
Mrna Levels ◽  
Glutamine Production

We determined the effects of 24-h recombinant human growth hormone (rhGH) infusion into a femoral artery on leg muscle protein kinetics, amino acid transport, and glutamine metabolism in eight adult hypercatabolic trauma patients. Metabolic pathways were assessed by leg arteriovenous catheterization and muscle biopsies with the use of stable amino acid isotopes. Muscle mRNA levels of selected enzymes were determined by competitive PCR. rhGH infusion significantly accelerated the inward transport rates of phenylalanine and leucine and protein synthesis, whereas the muscle protein degradation rate and cathepsin B and UbB polyubiquitin mRNA levels were not significantly modified by rhGH. rhGH infusion decreased the rate of glutamine de novo synthesis and glutamine precursor availability, total branched-chain amino acid catabolism, and nonprotein glutamate utilization. Thus net glutamine release from muscle into circulation significantly decreased after rhGH administration (∼50%), whereas glutamine synthetase mRNA levels increased after rhGH infusion, possibly to compensate for reduced glutamine precursor availability. We conclude that, after trauma, the anticatabolic action of rhGH is associated with a potentially harmful decrease in muscle glutamine production.

Kinetic impairment of nitrogen and muscle glutamine metabolisms in old glucocorticoid-treated rats

1999 ◽  
Vol 276 (3) ◽  
pp. E558-E564 ◽  
Author(s):  
Regine Minet-Quinard ◽  
Christophe Moinard ◽  
Françoise Villie ◽  
Stephane Walrand ◽  
Marie-Paule Vasson ◽  
...  
Keyword(s):  
Control Group ◽  
Synthetase Activity ◽  
Aged Rats ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Glucocorticoid Treatment ◽  
Sprague Dawley Rats ◽  
End Of Treatment ◽  
Catabolic State ◽  
Old Rats

Aged rats are more sensitive to injury, possibly through an impairment of nitrogen and glutamine (Gln) metabolisms mediated by glucocorticoids. We studied the metabolic kinetic response of adult and old rats during glucocorticoid treatment. The male Sprague-Dawley rats were 24 or 3 mo old. Both adult and old rats were divided into 7 groups. Groups labeled G3, G5, and G7 received, by intraperitoneal injection, 1.50 mg/kg of dexamethasone (Dex) for 3, 5, and 7 days, respectively. Groups labeled G3PF, G5PF, and G7PF were pair fed to the G3, G5, or G7 groups and were injected with an isovolumic solution of NaCl. One control group comprised healthy rats fed ad libitum. The response to aggression induced specifically by Dex (i.e., allowing for variations in pair-fed controls) appeared later in the aged rats (decrease in nitrogen balance from day 1 in adults but only from day 4 in old rats). The adult rats rapidly adapted to Dex treatment, whereas the catabolic state worsened until the end of treatment in the old rats. Gln homeostasis was not maintained in the aged rats; despite an early increase in muscular Gln synthetase activity, the Gln pool was depleted. These results suggest a kinetic impairment of both nitrogen and muscle Gln metabolisms in response to Dex with aging.

scholarly journals Nitrogen balance and myofibrillar protein turnover in double muscled Belgian Blue bulls in relation to compensatory growth after different periods of restricted feeding

1998 ◽  
Vol 78 (4) ◽  
pp. 549-559 ◽  
Author(s):  
C. Van Eenaeme ◽  
M. Evrard ◽  
J. L. Hornick ◽  
P. Baldwin ◽  
M. Diez ◽  
...  
Keyword(s):  
Nitrogen Balance ◽  
Compensatory Growth ◽  
Muscle Protein ◽  
Growth Period ◽  
Myofibrillar Protein ◽  
Control Group ◽  
Protein Breakdown ◽  
Low Protein ◽  
Fattening Period ◽  
Synthesis And Degradation

Nitrogen balance and myofibrillar protein breakdown were studied in 16 double-muscled Belgian Blue bulls during a low growth period (0.5 kg d−1) (LGP) of 4 mo (L4), 8 mo (L8), or 14 mo (L14) and the subsequent fattening period (rapid growth period, RGP). The control group (CG) was given a conventional fattening diet; the others received a low-energy, low-protein diet during LGP, and the same diet as the CG during RGP. Measurements were made halfway through the LGP, l mo after the beginning of the fattening period, and 1 mo before slaughter. Nitrogen balance was about half of CG (P < 0.001) during LGP, e.g., 50.8, 21.3, 25.8, and 23.8 g d−1, for CG, L4, L8, and L14, respectively. Between LGP and RGP, N balance increased by about 18 g N d−1 above the control in the compensating groups L4, L8 and L14. This was due to the higher digestibility and the higher metabolizability of the nitrogen in the fattening diet. Lower muscle protein accretion during the LGP resulted from decreased synthesis (P < 0.001) and degradation (P < 0.05) compared with the GC. When changing to RGP different evolution patterns were observed in the three formerly restricted groups, e.g. after a short restriction (L4) both synthesis and degradation rose during the RGP but declined towards the end. After a longer restriction (L8 and L14), synthesis and degradation increased and remained high. The magnitude of these increases was inversely proportional to the length of the restriction period. Key words: Belgian Blue bulls, compensatory growth, nitrogen balance, muscle, muscle protein breakdown

scholarly journals Glucocorticoid effects on insulin- and IGF-I-regulated muscle protein metabolism during aging

1998 ◽  
Vol 156 (1) ◽  
pp. 83-89 ◽  
Author(s):  
D Dardevet ◽  
C Sornet ◽  
I Savary ◽  
E Debras ◽  
P Patureau-Mirand ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Atrophy ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Recovery Period ◽  
Adult Rats ◽  
Igf I ◽  
Muscle Protein Metabolism ◽  
Old Rats

This study was performed to assess the effect of glucocorticoids (dexamethasone) on insulin- and IGF-I-regulated muscle protein metabolism in adult and old rats. Muscle atrophy occurred more rapidly in old rats, and recovery of muscle mass was impaired when compared with adults. Muscle wasting resulted mainly from increased protein breakdown in adult rat but from depressed protein synthesis in the aged animal. Glucocorticoid treatment significantly decreased the stimulatory effect of insulin and IGF-I on muscle protein synthesis in adult rats by 25.9 and 58.1% respectively. In old rats, this effect was even greater, being 49.3 and 100% respectively. With regard to muscle proteolysis, glucocorticoids blunted the anti-proteolytic action of insulin and IGF-I in both age groups. During the recovery period, adult rats reversed the glucocorticoid-induced resistance of muscle protein metabolism within 3 days, at which time old rats still exhibited the decrease in insulin-regulated proteolysis. In conclusion, the higher sensitivity of old rat muscle to glucocorticoids may in part result from the greater modification of the effects of insulin and IGF-I on muscle protein metabolism. These responses to glucocorticoids in old rats may be associated with the emergence of muscle atrophy with advancing age.

Corticosteroids increase glutamine utilization in human splanchnic bed

2008 ◽  
Vol 294 (2) ◽  
pp. G548-G553 ◽  
Author(s):  
Ronan Thibault ◽  
Susan Welch ◽  
Nelly Mauras ◽  
Brenda Sager ◽  
Astride Altomare ◽  
...  
Keyword(s):  
De Novo ◽  
Inflammatory Diseases ◽  
The Body ◽  
Glutamine Metabolism ◽  
Severe Illness ◽  
Control Group ◽  
High Dose ◽  
Isotope Tracer ◽  
Healthy Humans ◽  
Tracer Methods

Glutamine is the most abundant amino acid in the body and is extensively taken up in gut and liver in healthy humans. To determine whether glucocorticosteroids alter splanchnic glutamine metabolism, the effect of prednisone was assessed in healthy volunteers using isotope tracer methods. Two groups of healthy adults received 5-h intravenous infusions of l-[1-14C]leucine and l-[2H5]glutamine, along with q. 20 min oral sips of tracer doses of l-[1-13C]glutamine in the fasting state, either 1) at baseline (control group; n = 6) or 2) after a 6-day course of 0.8 mg·kg−1·day−1 prednisone (prednisone group; n = 8). Leucine and glutamine appearance rates (Ra) were determined from plasma [1-14C]ketoisocaproate and [2H5]glutamine, respectively, and leucine and glutamine oxidation from breath 14CO2 and 13CO2, respectively. Splanchnic glutamine extraction was estimated by the fraction of orally administered [13C]glutamine that failed to appear into systemic blood. Prednisone treatment 1) did not affect leucine Ra or leucine oxidation; 2) increased plasma glutamine Ra, mostly owing to enhanced glutamine de novo synthesis (medians ± interquartiles, 412 ± 61 vs. 280 ± 190 μmol·kg−1·h−1, P = 0.003); and 3) increased the fraction of orally administered glutamine undergoing extraction in the splanchnic territory (means ± SE 64 ± 6 vs. 42 ± 12%, P < 0.05), without any change in the fraction of glutamine oxidized (means ± SE, 75 ± 4 vs. 77 ± 4%, not significant). We conclude that high-dose glucocorticosteroids increase in splanchnic bed the glutamine requirements. The role of such changes in patients receiving chronic corticoid treatment for inflammatory diseases or suffering from severe illness remains to be determined.

Effect of exercise and recovery on muscle protein synthesis in human subjects

1990 ◽  
Vol 259 (4) ◽  
pp. E470-E476 ◽  
Author(s):  
F. Carraro ◽  
C. A. Stuart ◽  
W. H. Hartl ◽  
J. Rosenblatt ◽  
R. R. Wolfe
Keyword(s):  
Protein Synthesis ◽  
Aerobic Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Nitrogen Excretion ◽  
Control Group ◽  
Protein Breakdown ◽  
Muscle Protein Breakdown ◽  
Synthetic Rate ◽  
Fractional Synthetic Rate

Previous studies using indirect means to assess the response of protein metabolism to exercise have led to conflicting conclusions. Therefore, in this study we have measured the rate of muscle protein synthesis in normal volunteers at rest, at the end of 4 h of aerobic exercise (40% maximal O2 consumption), and after 4 h of recovery by determining directly the rate of incorporation of 1,2-[13C]leucine into muscle. The rate of muscle protein breakdown was assessed by 3-methylhistidine (3-MH) excretion, and total urinary nitrogen excretion was also measured. There was an insignificant increase in 3-MH excretion in exercise of 37% and a significant increase (P less than 0.05) of 85% during 4 h of recovery from exercise (0.079 +/- 0.008 vs. 0.147 +/- 0.0338 mumol.kg-1.min-1 for rest and recovery from exercise, respectively). Nonetheless, there was no effect of exercise on total nitrogen excretion. Muscle fractional synthetic rate was not different in the exercise vs. the control group at the end of exercise (0.0417 +/- 0.004 vs. 0.0477 +/- 0.010%/h for exercise vs. control), but there was a significant increase in fractional synthetic rate in the exercise group during the recovery period (0.0821 +/- 0.006 vs. 0.0654 +/- 0.012%/h for exercise vs. control, P less than 0.05). Thus we conclude that although aerobic exercise may stimulate muscle protein breakdown, this does not result in a significant depletion of muscle mass because muscle protein synthesis is stimulated in recovery.

Effect of pyruvate on the metabolic regulation of nitrogenase activity in Rhodospirillum rubrum in darkness

Microbiology ◽  
2011 ◽  
Vol 157 (6) ◽  
pp. 1834-1840 ◽  
Author(s):  
Tiago Toscano Selao ◽  
Tomas Edgren ◽  
He Wang ◽  
Agneta Norén ◽  
Stefan Nordlund
Keyword(s):  
Nitrogen Source ◽  
Metabolic Regulation ◽  
Rhodospirillum Rubrum ◽  
De Novo ◽  
Nitrogenase Activity ◽  
Signal Transduction Pathway ◽  
Nitrogen Sources ◽  
Synthetase Activity ◽  
Glutamine Synthetase Activity ◽  
Fe Protein

Rhodospirillum rubrum, a photosynthetic diazotroph, is able to regulate nitrogenase activity in response to environmental factors such as ammonium ions or darkness, the so-called switch-off effect. This is due to reversible modification of the Fe-protein, one of the two components of nitrogenase. The signal transduction pathway(s) in this regulatory mechanism is not fully understood, especially not in response to darkness. We have previously shown that the switch-off response and metabolic state differ between cells grown with dinitrogen or glutamate as the nitrogen source, although both represent poor nitrogen sources. In this study we show that pyruvate affects the response to darkness in cultures grown with glutamate as nitrogen source, leading to a response similar to that in cultures grown with dinitrogen. The effects are related to PII protein uridylylation and glutamine synthetase activity. We also show that pyruvate induces de novo protein synthesis and that inhibition of pyruvate formate-lyase leads to loss of nitrogenase activity in the dark.

scholarly journals Effect of glucose deprivation on rat glutamine synthetase in cultured astrocytes

1996 ◽  
Vol 315 (2) ◽  
pp. 607-612 ◽  
Author(s):  
Françoise ROSIER ◽  
Dominique LAMBERT ◽  
Jeannine MERTENS-STRIJTHAGEN
Keyword(s):  
Glutamine Synthetase ◽  
Specific Activity ◽  
Glucose Deprivation ◽  
Synthesis Rate ◽  
Synthetase Activity ◽  
Glutamine Synthetase Activity ◽  
Sprague Dawley ◽  
Experimental Conditions ◽  
Adult Rats ◽  
Total Recovery

Glutamine synthetase was purified from the cerebral cortex of adult rats and characterized. Polyclonal rabbit antibodies were raised against the enzyme, purified and their specific anti-(glutamine synthetase) activity determined. A primary astroglial culture was prepared from newborn Sprague–Dawley rats. Astrocytes at different ages of development were incubated in the presence and absence of glucose. In glucose-deprived conditions the specific activity of glutamine synthetase decreased. This decrease was more pronounced in 8-day-old than in 21-day-old cultures. Kinetic analysis demonstrated that the reduction in activity was mainly related to a decrease in Vmax. By immunoprecipitation, it was shown that the number of enzyme molecules in astrocytes was decreased in glucose-deprived conditions. On addition of glucose, a total recovery of glutamine synthetase was obtained after 36 h in 8-day-old culture. Rates of degradation and synthesis were investigated. When compared with an incubation in the presence of glucose, glucose deprivation increased enzyme turnover, as estimated from the first-order disappearance of radioactivity from glutamine synthetase. Synthesis rate was estimated from the incorporation of [35S]methionine during a 2 h incubation period and was decreased in glucose-deprived conditions. Trichloroacetate-precipitable proteins changed only slightly in the experimental conditions, and total protein did not vary significantly during the experimental period. A mathematical model is presented which attempts to integrate degradation and synthesis in our experimental model.

scholarly journals Submitochondrial localization and function of enzymes of glutamine metabolism in avian liver.

1977 ◽  
Vol 73 (2) ◽  
pp. 300-310 ◽  
Author(s):  
J E Vorhaben ◽  
J W Campbell
Keyword(s):  
Glutamine Synthetase ◽  
Glutamate Dehydrogenase ◽  
Liver Mitochondria ◽  
Glutamine Metabolism ◽  
Synthetase Activity ◽  
Glutamine Synthetase Activity ◽  
The Matrix ◽  
Matrix Compartment ◽  
Matrix Fraction ◽  
And Function

Glutamine synthetase (EC 6.3.1.2) was localized within the matrix compartment of avian liver mitochondria. The submitochondrial localization of this enzyme was determined by the digitonin-Lubrol method of Schnaitman and Greenawalt (35). The matrix fraction contained over 74% of the glutamine synthetase activity and the major proportion of the matirx marker enzymes, malate dehydrogenase (71%), NADP-dependent isocitrate dehydrogenase (83%), and glutamate dehydrogenase (57%). The highest specific activities of these enzymes were also found in the matrix compartment. Oxidation of glutamine by avian liver mitochondria was substantially less than that of glutamate. Bromofuroate, an inhibitor of glutamate dehydrogenase, blocked oxidation of glutamate and of glutamine whereas aminoxyacetate, a transaminase inhibitor, had little or no effect with either substrate. These results indicate that glutamine metabolism is probably initiated by the conversion of glutamine to glutamate rather than to an alpha-keto acid. The localization of a glutaminase activity within avian liver mitochondria plus the absence of an active mitochondrial glutamine transaminase is consistent with the differential effects of the transaminase and glutamate dehydrogenase inhibitors. The high glutamine synthetase activity (40:1) suggests that mitochondrial catabolism of glutamine is minimal, freeing most of the glutamine synthesized for purine (uric acid) biosynthesis.

Continuous Epidural Blockade Arrests the Postoperative Decrease in Muscle Protein Fractional Synthetic Rate in Surgical Patients 

1997 ◽  
Vol 86 (5) ◽  
pp. 1033-1040 ◽  
Author(s):  
Franco Carli ◽  
Dave Halliday
Keyword(s):  
Protein Synthesis ◽  
Local Anesthetics ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Sensory Block ◽  
Control Group ◽  
Protein Breakdown ◽  
Epidural Group ◽  
Synthetic Rate ◽  
Fractional Synthetic Rate

Background Epidural anesthesia with local anesthetics is associated with postoperative attenuation of nitrogen loss. The protein-sparing effect could be the result of either a decreased protein breakdown or increased protein synthesis. Although the role of epidural local anesthetics in effectively limiting the increase in postoperative protein breakdown is established at the whole-body level, it is necessary to determine whether the muscle protein fractional synthetic rate is directly modulated when nociceptive stimuli are blocked. Methods Twelve otherwise healthy patients scheduled for elective colorectal surgery, who were receiving a constant intake of nitrogen (0.1 kg-1.day-1) and calories (20 kcal.kg-1.day-1) before and after surgery, were randomly assigned to receive either general anesthesia (with thiopentone, vecuronium, fentanyl, or enflurane; control group, n = 6) or epidural anesthesia (T3-S5 sensory block with 0.75% bupivacaine) and general anesthesia (epidural group, n = 6). In the control group, postoperative analgesia was achieved with papaveretum given subcutaneously, whereas a continuous epidural bupivacaine infusion (T8-L5 sensory block) was maintained for 48 h in the epidural group. The postabsorptive muscle protein fractional synthetic rate was determined using a 6-h continuous infusion of 13C-labeled leucine (1 mg.kg-1.h-1), and the 13C enrichment in muscle biopsy specimens before surgery and 48 h after surgery was measured. Results Plateau 13C enrichment of plasma alpha-ketoisocaproate (taken to represent the intracellular leucine precursor pool enrichment for protein synthesis) was achieved during the 6-h infusion (mean coefficient of variation was 2.8%). Muscle protein synthesis at 48 h after operation compared with preoperative levels decreased significantly in the control group (P = 0.03). In contrast, it increased by 25% in the epidural group. Although this was not significantly (P = 0.15) different from preoperative levels, it was significantly greater than in the control patients. Conclusions Epidural infusion of local anesthetics begun before surgery and continued during the first 48 h after operation significantly attenuates the decrease in the postabsorptive muscle protein synthesis rate associated with surgical injury. Effective block of nociceptive stimuli thus preserves tissue protein synthesis.

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