The aim was to determine the effects of enhanced availability of branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) on ammonia detoxification to glutamine (GLN) and protein metabolism in two types of skeletal muscle under hyperammonemic conditions. Isolated soleus (SOL, slow-twitch) and extensor digitorum longus (EDL, fast-twitch) muscles from the left leg of white rats were incubated in a medium with 1 mM ammonia (NH3 group), BCAAs at four times the concentration of the controls (BCAA group) or high levels of both ammonia and BCAA (NH3 + BCAA group). The muscles from the right leg were incubated in basal medium and served as paired controls. L-[1-14C]leucine was used to estimate protein synthesis and leucine oxidation, and 3-methylhistidine release was used to evaluate myofibrillar protein breakdown. We observed decreased protein synthesis and glutamate and α-ketoglutarate (α-KG) levels and increased leucine oxidation, GLN levels, and GLN release into medium in muscles in NH3 group. Increased leucine oxidation, release of branched-chain keto acids and GLN into incubation medium, and protein synthesis in EDL were observed in muscles in the BCAA group. The addition of BCAAs to medium eliminated the adverse effects of ammonia on protein synthesis and adjusted the decrease in α-KG found in the NH3 group. We conclude that (i) high levels of ammonia impair protein synthesis, activate BCAA catabolism, enhance GLN synthesis, and decrease glutamate and α-KG levels and (ii) increased BCAA availability enhances GLN release from muscles and attenuates the adverse effects of ammonia on protein synthesis and decrease in α-KG.

• MeSH
• amoniak otrava   MeSH
• citrátový cyklus účinky léků   MeSH
• glutamin agonisté   metabolismus   MeSH
• hyperamonemie enzymologie   metabolismus   patofyziologie   MeSH
• jaterní cirhóza etiologie   metabolismus   MeSH
• kyseliny ketoglutarové metabolismus   MeSH
• methylhistidiny metabolismus   MeSH
• orgánová specificita MeSH
• osmolární koncentrace MeSH
• oxidace-redukce MeSH
• potkani Wistar MeSH
• proteolýza účinky léků   MeSH
• proteosyntéza účinky léků   MeSH
• radioizotopy uhlíku MeSH
• svalová vlákna typu I účinky léků   enzymologie   metabolismus   MeSH
• svalová vlákna typu II účinky léků   enzymologie   metabolismus   MeSH
• svalové proteiny genetika   metabolismus   MeSH
• techniky in vitro MeSH
• větvené aminokyseliny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

BACKGROUND: Enhanced glutamine (GLN) intake may affect the catabolism of branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), which play a regulatory role in protein turnover. We examined the effects of enhanced GLN availability on leucine oxidation, amino acid concentrations, and protein metabolism in muscles from healthy and septic rats. METHODS: Cecal ligation and puncture were used as a model of sepsis. Twenty-four hours after surgery, the soleus (SOL, red muscle) and the extensor digitorum longus (EDL, white muscle) were incubated in medium containing 0.5 or 2.0 mM GLN. Protein breakdown, protein synthesis, and leucine oxidation were determined via 3-methylhistidine release, muscle L-[1-(14)C]leucine radioactivity, and the radioactivity of released (14)CO2, respectively. RESULTS: In muscles from septic animals, increased proteolysis and leucine oxidation and decreased protein synthesis were detected. These effects were more pronounced in the EDL. In septic muscles, the addition of GLN decreased leucine oxidation in both muscles and increased protein synthesis in the EDL. In muscles from untreated animals, decreased leucine oxidation after the addition of GLN to the medium was associated with decreased protein synthesis in the SOL and decreased concentrations of serine, glycine, histidine, alanine, arginine, proline, and lysine in both muscles. CONCLUSIONS: White muscle fibers are more sensitive to septic stimuli than red fibers are. In sepsis, enhanced GLN intake may ameliorate GLN deficiency, inhibit BCAA catabolism, and stimulate protein synthesis. In the healthy state, surplus of GLN may lead to severe alterations in the intramuscular concentration of several amino acids and impair protein synthesis.

• MeSH
• aminokyseliny metabolismus   MeSH
• glutamin aplikace a dávkování   nedostatek   farmakokinetika   MeSH
• kosterní svaly účinky léků   metabolismus   MeSH
• krysa rodu rattus MeSH
• leucin metabolismus   MeSH
• methylhistidiny metabolismus   MeSH
• potkani Wistar MeSH
• potravní doplňky MeSH
• proteiny metabolismus   MeSH
• proteosyntéza účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• viscerální proteiny, 3-metylhistidin,
• MeSH
• albuminy metabolismus   nedostatek   MeSH
• C-reaktivní protein metabolismus   MeSH
• financování organizované MeSH
• HDL-cholesterol krev   metabolismus   MeSH
• klinické laboratorní techniky metody   využití   MeSH
• kreatinin metabolismus   moč   MeSH
• LDL-cholesterol krev   metabolismus   MeSH
• lidé MeSH
• mastné kyseliny metabolismus   MeSH
• metabolický syndrom * etiologie   metabolismus   MeSH
• methylhistidiny metabolismus   MeSH
• oxidační stres MeSH
• pilotní projekty MeSH
• protein-energetická malnutrice * metabolismus   MeSH
• proteiny metabolismus   MeSH
• statistika jako téma MeSH
• Check Tag
• lidé MeSH