Enhanced Glutamine Availability Exerts Different Effects on Protein and Amino Acid Metabolism in Skeletal Muscle From Healthy and Septic Rats

Holeček, Milan; Šišpera, Luděk; Skalská, H

doi:10.1177/0148607114537832

Cited by 18 publications

(17 citation statements)

References 46 publications

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“…This possibility has been confirmed in recent studies demonstrating that extracellular GLN deficiency enhances GLN release from muscle and activates BCAA catabolism while BCAA oxidation in muscles incubated in medium with high GLN concentration is inhibited (Holecek & Sispera ; Holecek et al . ). However, increased GLN concentrations and leucine oxidation in muscles incubated with PB suggest that the cause of BCAA deficiency in blood and muscles after PB treatment is different.…”

Section: Discussionmentioning

confidence: 97%

Acute effects of phenylbutyrate on glutamine, branched‐chain amino acid and protein metabolism in skeletal muscles of rats

Holeček

Vodeničarovová

Šiman

2017

Int J Experimental Path

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Phenylbutyrate (PB) acts as chemical chaperone and histone deacetylase inhibitor, which is used to decrease ammonia in urea cycle disorders and has been investigated for use in the treatment of a number of lethal illnesses. We performed in vivo and in vitro experiments to examine the effects of PB on glutamine (GLN), branched-chain amino acid (BCAA; valine, leucine and isoleucine) and protein metabolism in rats. In the first study, animals were sacrificed one hour after three injections of PB (300mg/kg b.w.) or saline. In the second study, soleus (SOL, slow twitch) and extensor digitorum longus (EDL, fast twitch) muscles were incubated in a medium with or without PB (5 mM). L-[1- C] leucine was used to estimate protein synthesis and leucine oxidation, and 3-methylhistidine release was used to evaluate myofibrillar protein breakdown. PB treatment decreased GLN, BCAA and branched-chain keto acids (BCKAs) in blood plasma, decreased BCAA and increased GLN concentrations in muscles, and increased GLN synthetase activities in muscles. Addition of PB to incubation medium increased leucine oxidation (55% in EDL, 29% in SOL), decreased BCKA and increased GLN in medium of both muscles, increased GLN in muscles, decreased protein synthesis in SOL and increased proteolysis in EDL. It is concluded that PB decreases BCAA, BCKA and GLN in blood plasma, activates BCAA catabolism and GLN synthesis in muscle and exerts adverse effects on protein metabolism. The results indicate that BCAA and GLN supplementation is needed when PB is used therapeutically and that PB may be a useful prospective agent which could be effective in management of maple syrup urine disease.

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Section: Discussionmentioning

confidence: 97%

Acute effects of phenylbutyrate on glutamine, branched‐chain amino acid and protein metabolism in skeletal muscles of rats

Holeček

Vodeničarovová

Šiman

2017

Int J Experimental Path

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“…Sarcopenia, defined as the age‐related loss of muscle mass and strength, was a main factor in the reduced ability to increase skeletal muscle synthesis of amino acids and proteins in response to biological responses of the immunity system . Considering the important role of muscles in the metabolism of amino acids, muscle proteins turn over slowly and there are minimal diurnal changes in the size of the muscle protein pool in response to feeding and fasting . Besides, amino acids liberated from the protein pool are used for synthesis of tricarboxylic acid (TCA) cycle intermediates and glutamine.…”

Section: Discussionmentioning

confidence: 99%

“…The carbon skeleton of the other amino acids is used for synthesis of TCA cycle intermediates and glutamine. These six amino acids provide amino groups and ammonia for the synthesis of glutamine and alanine, which are subsequently released in excessive amounts by muscle tissues . Meanwhile, glutamine, a final product synthesized by muscles from the metabolism of these various amino acids, is an important fuel and regulator of DNA and RNA synthesis in mucosal cells and immune system cells and fulfils several other important functions in human metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…The alanine aminotransferase reaction establishes and maintains high concentrations of TCA cycle intermediates and high TCA cycle flux in the early phase of stressed conditions such as surgery. It is proposed that maximal values in the TCA cycle are reduced because of insufficient TCA cycle anaplerosis such as muscle deficiency (quality or quantity) and that this also presents a limitation for the maximal rate of fatty acid oxidation . In conclusion, interactions between the amino acid pool and the TCA cycle may play a central role in energy metabolism in muscle.…”

Section: Discussionmentioning

confidence: 99%

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Profile of plasma amino acids values as a predictor of sepsis in patients following living donor liver transplantation: Special reference to sarcopenia and postoperative early nutrition

Toshima

Shirabe

Kurihara

et al. 2015

Hepatology Research

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“…Muscle mass depletion is known to be the main factor in a decreased ability to increase skeletal muscle synthesis of amino acids and proteins in response to biologic change of the immune system [21, 22]. Risk of muscle mass depletion for infection can be explained as playing a substantial role in the skeletal muscle, with respect to the metabolism of amino acids or activation of immunity in infectious conditions and the importance of immune system induction by amino acids [18].…”

Section: Discussionmentioning

confidence: 99%

Muscle Mass Depletion Associated with Poor Outcome of Sepsis in the Emergency Department

et al. 2018

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Background/Aims: Muscle mass depletion has been suggested to predict morbidity and mortality in various diseases. However, it is not well known whether muscle mass depletion is associated with poor outcome in sepsis. We hypothesized that muscle mass depletion is associated with poor outcome in sepsis. Methods: Retrospective observational study was conducted in an emergency department during a 9-year period. Medical records of 627 patients with sepsis were reviewed. We divided the patients into 2 groups according to 28-day mortality and compared the presence of muscle mass depletion assessed by the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on abdomen CT scans. Univariate and multivariate logistic regression analyses were conducted to examine the association of scarcopenia on the outcome of sepsis. Results: A total of 274 patients with sepsis were finally included in the study: 45 (16.4%) did not survive on 28 days and 77 patients (28.1%) were identified as having muscle mass depletion. The presence of muscle mass depletion was independently associated with 28-day mortality on multivariate logistic analysis (OR 2.79; 95% CI 1.35–5.74, p = 0.01). Conclusions: Muscle mass depletion evaluated by CT scan was associated with poor outcome of sepsis patients. Further studies on the appropriateness of specific treatment for muscle mass depletion with sepsis are needed.

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Enhanced Glutamine Availability Exerts Different Effects on Protein and Amino Acid Metabolism in Skeletal Muscle From Healthy and Septic Rats

Cited by 18 publications

References 46 publications

Acute effects of phenylbutyrate on glutamine, branched‐chain amino acid and protein metabolism in skeletal muscles of rats

Acute effects of phenylbutyrate on glutamine, branched‐chain amino acid and protein metabolism in skeletal muscles of rats

Profile of plasma amino acids values as a predictor of sepsis in patients following living donor liver transplantation: Special reference to sarcopenia and postoperative early nutrition

Muscle Mass Depletion Associated with Poor Outcome of Sepsis in the Emergency Department

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