Alanine and glutamine are the principal glucogenic amino acids. Most originate from muscles, where branched-chain amino acids (valine, leucine, and isoleucine) are nitrogen donors and, under exceptional circumstances, a source of carbons for glutamate synthesis. Glutamate is a nitrogen source for alanine synthesis from pyruvate and a substrate for glutamine synthesis by glutamine synthetase. The following differences between alanine and glutamine, which can play a role in their use in gluconeogenesis, are shown: (i) glutamine appearance in circulation is higher than that of alanine; (ii) the conversion to oxaloacetate, the starting substance for glucose synthesis, is an ATP-consuming reaction for alanine, which is energetically beneficial for glutamine; (iii) most alanine carbons, but not glutamine carbons, originate from glucose; and (iv) glutamine acts a substrate for gluconeogenesis in the liver, kidneys, and intestine, whereas alanine does so only in the liver. Alanine plays a significant role during early starvation, exposure to high-fat and high-protein diets, and diabetes. Glutamine plays a dominant role in gluconeogenesis in prolonged starvation, acidosis, liver cirrhosis, and severe illnesses like sepsis and acts as a substrate for alanine synthesis in the small intestine. Interactions among muscles and the liver, kidneys, and intestine ensuring optimal alanine and glutamine supply for gluconeogenesis are suggested.

• Klíčová slova
• branched-chain amino acids, cirrhosis, diabetes, glucose, starvation,
• MeSH
• alanin * metabolismus   MeSH
• glukoneogeneze * MeSH
• glukosa metabolismus   MeSH
• glutamin * metabolismus   MeSH
• játra * metabolismus   MeSH
• ledviny * metabolismus   MeSH
• lidé MeSH
• tenké střevo * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• alanin * MeSH
• glukosa MeSH
• glutamin * MeSH

The article shows that skeletal muscle plays a dominant role in the catabolism of branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) and the pathogenesis of their decreased concentrations in liver cirrhosis, increased concentrations in diabetes, and nonspecific alterations in disorders with signs of systemic inflammatory response syndrome (SIRS), such as burn injury and sepsis. The main role of skeletal muscle in BCAA catabolism is due to its mass and high activity of BCAA aminotransferase, which is absent in the liver. Decreased BCAA levels in liver cirrhosis are due to increased use of the BCAA as a donor of amino group to alpha-ketoglutarate for synthesis of glutamate, which in muscles acts as a substrate for ammonia detoxification to glutamine. Increased BCAA levels in diabetes are due to alterations in glycolysis, citric acid cycle, and fatty acid oxidation. Decreased glycolysis and citric cycle activity impair BCAA transamination to branched-chain keto acids (BCKAs) due to decreased supply of amino group acceptors (alpha-ketoglutarate, pyruvate, and oxaloacetate); increased fatty acid oxidation inhibits flux of BCKA through BCKA dehydrogenase due to increased supply of NADH and acyl-CoAs. Alterations in BCAA levels in disorders with SIRS are inconsistent due to contradictory effects of SIRS on muscles. Specifically, increased proteolysis and insulin resistance tend to increase BCAA levels, whereas activation of BCKA dehydrogenase and glutamine synthesis tend to decrease BCAA levels. The studies are needed to elucidate the role of alterations in BCAA metabolism and the effects of BCAA supplementation on the outcomes of specific diseases.

• MeSH
• diabetes mellitus metabolismus   MeSH
• isoleucin metabolismus   MeSH
• jaterní cirhóza metabolismus   MeSH
• kosterní svaly metabolismus   MeSH
• leucin metabolismus   MeSH
• lidé MeSH
• metabolické nemoci metabolismus   MeSH
• valin metabolismus   MeSH
• větvené aminokyseliny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• isoleucin MeSH
• leucin MeSH
• valin MeSH
• větvené aminokyseliny MeSH

Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) are essential amino acids with protein anabolic properties, which have been studied in a number of muscle wasting disorders for more than 50 years. However, until today, there is no consensus regarding their therapeutic effectiveness. In the article is demonstrated that the crucial roles in BCAA metabolism play: (i) skeletal muscle as the initial site of BCAA catabolism accompanied with the release of alanine and glutamine to the blood; (ii) activity of branched-chain keto acid dehydrogenase (BCKD); and (iii) amination of branched-chain keto acids (BCKAs) to BCAAs. Enhanced consumption of BCAA for ammonia detoxification to glutamine in muscles is the cause of decreased BCAA levels in liver cirrhosis and urea cycle disorders. Increased BCKD activity is responsible for enhanced oxidation of BCAA in chronic renal failure, trauma, burn, sepsis, cancer, phenylbutyrate-treated subjects, and during exercise. Decreased BCKD activity is the main cause of increased BCAA levels and BCKAs in maple syrup urine disease, and plays a role in increased BCAA levels in diabetes type 2 and obesity. Increased BCAA concentrations during brief starvation and type 1 diabetes are explained by amination of BCKAs in visceral tissues and decreased uptake of BCAA by muscles. The studies indicate beneficial effects of BCAAs and BCKAs in therapy of chronic renal failure. New therapeutic strategies should be developed to enhance effectiveness and avoid adverse effects of BCAA on ammonia production in subjects with liver cirrhosis and urea cycle disorders. Further studies are needed to elucidate the effects of BCAA supplementation in burn, trauma, sepsis, cancer and exercise. Whether increased BCAA levels only markers are or also contribute to insulin resistance should be known before the decision is taken regarding their suitability in obese subjects and patients with type 2 diabetes. It is concluded that alterations in BCAA metabolism have been found common in a number of disease states and careful studies are needed to elucidate their therapeutic effectiveness in most indications.

• Klíčová slova
• Ammonia, Cachexia, Cirrhosis, Diabetes, Glutamine, Nutrition,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the essential amino acid leucine that has been reported to have anabolic effects on protein metabolism. The aims of this article were to summarize the results of studies of the effects of HMB on skeletal muscle and to examine the evidence for the rationale to use HMB as a nutritional supplement to exert beneficial effects on muscle mass and function in various conditions of health and disease. The data presented here indicate that the beneficial effects of HMB have been well characterized in strength-power and endurance exercise. HMB attenuates exercise-induced muscle damage and enhances muscle hypertrophy and strength, aerobic performance, resistance to fatigue, and regenerative capacity. HMB is particularly effective in untrained individuals who are exposed to strenuous exercise and in trained individuals who are exposed to periods of high physical stress. The low effectiveness of HMB in strength-trained athletes could be due to the suppression of the proteolysis that is induced by the adaptation to training, which may blunt the effects of HMB. Studies performed with older people have demonstrated that HMB can attenuate the development of sarcopenia in elderly subjects and that the optimal effects of HMB on muscle growth and strength occur when it is combined with exercise. Studies performed under in vitro conditions and in various animal models suggest that HMB may be effective in treatment of muscle wasting in various forms of cachexia. However, there are few clinical reports of the effects of HMB on muscle wasting in cachexia; in addition, most of these studies evaluated the therapeutic potential of combinations of various agents. Therefore, it has not been possible to determine whether HMB was effective or if there was a synergistic effect. Although most of the endogenous HMB is produced in the liver, there are no reports regarding the levels and the effects of HMB supplementation in subjects with liver disease. Several studies have suggested that anabolic effects of HMB supplementation on skeletal muscle do not occur in healthy, non-exercising subjects. It is concluded that (i) HMB may be applied to enhance increases in the mass and strength of skeletal muscles in subjects who exercise and in the elderly and (ii) studies examining the effects of HMB administered alone are needed to obtain conclusions regarding the specific effectiveness in attenuating muscle wasting in various muscle-wasting disorders.

• Klíčová slova
• Cachexia, Exercise, HMB, Leucine, Sarcopenia, Supplements,
• MeSH
• kachexie dietoterapie   patofyziologie   MeSH
• kosterní svaly účinky léků   fyziologie   MeSH
• lidé MeSH
• potravní doplňky MeSH
• sarkopenie dietoterapie   patofyziologie   MeSH
• svalová atrofie dietoterapie   patofyziologie   MeSH
• svalová síla účinky léků   MeSH
• syndrom chřadnutí dietoterapie   patofyziologie   MeSH
• valeráty aplikace a dávkování   farmakologie   MeSH
• zdraví MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• beta-hydroxyisovaleric acid MeSH Prohlížeč
• valeráty MeSH

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-[1-14 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.

• Klíčová slova
• Phenylbutyrate, branched-chain amino acids, glutamine, leucine, maple syrup urine disease, muscle protein,
• MeSH
• fenylbutyráty farmakologie   MeSH
• glutamin metabolismus   MeSH
• kosterní svaly účinky léků   metabolismus   MeSH
• leucin metabolismus   MeSH
• oxidace-redukce účinky léků   MeSH
• potkani Wistar MeSH
• proteosyntéza účinky léků   MeSH
• svalové proteiny metabolismus   MeSH
• techniky tkáňových kultur MeSH
• větvené aminokyseliny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fenylbutyráty MeSH
• glutamin MeSH
• leucin MeSH
• svalové proteiny MeSH
• větvené aminokyseliny MeSH

Endotoxin administration is frequently used as a model of systemic inflammatory response which is considered the important pathogenetic factor in muscle wasting development in severe illness, such as sepsis, cancer, injury, AIDS and others. The main purpose of this study was determining the effect of various doses of endotoxin on protein and amino acid metabolism in two types of rat skeletal muscle. Sepsis was induced by intraperitoneal administration of endotoxin in a dose of 1, 3 and 5 mg/kg body weight (bw); control animals received a corresponding volume of the saline solution. After 24 h, extensor digitorum longus (EDL) and soleus (SOL) muscles were isolated and used for determination of total and myofibrillar proteolysis, protein synthesis, activity of cathepsins B and L, chymotrypsin-like activity of proteasome and amino acid release. The endotoxemia induced the body weight loss, the rise of total cholesterol and triglyceride plasma concentration and the protein catabolic state in skeletal muscle, which was caused by a higher increase in protein breakdown (due to activation of the proteasome system) than protein synthesis. The more significant effect of endotoxin was seen in EDL than SOL. The dose of 5 mg of endotoxin/kg bw induced the most significant changes in parameters of the protein and amino acid metabolism measured and could be therefore considered appropriate for studies of protein catabolism in young rat skeletal muscle at 24 h after endotoxin treatment.

• MeSH
• endotoxiny farmakologie   MeSH
• kathepsin B metabolismus   MeSH
• kosterní svaly metabolismus   MeSH
• krysa rodu Rattus MeSH
• myofibrily metabolismus   MeSH
• potkani Wistar MeSH
• proteasomový endopeptidasový komplex metabolismus   MeSH
• sepse metabolismus   MeSH
• svalové proteiny metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• endotoxiny MeSH
• kathepsin B MeSH
• proteasomový endopeptidasový komplex MeSH
• svalové proteiny MeSH

β-Hydroxy-β-methylbutyrate (HMB) is a leucine metabolite that may have a positive effect in protein catabolic conditions. Therefore, we hypothesized that HMB treatment could attenuate the sepsis-induced protein catabolic state. The aims of our study were to elucidate the effect of HMB in healthy and septic animals and to evaluate the differences in the action of HMB in different muscle types. Intact and septic (5 mg endotoxin/kg i.p.) rats were administered with HMB (0.5 g/kg/day) or saline. After 24 h, extensor digitorum longus (EDL) and soleus (SOL) muscles were isolated and used for determination of total and myofibrillar proteolysis, protein synthesis, leucine oxidation, activity of cathepsins B and L, chymotrypsin-like activity, and expression of α-subunits of proteasome. Our results indicate that the catabolic state induced by the endotoxin treatment was caused both by increase in protein breakdown (due to activation of proteasome system) and by attenuation of protein synthesis. The EDL (muscle composed of white, fast-twitch fibers) was more susceptible to these changes than the SOL (muscle composed of red, slow-twitch fibers). The HMB treatment had no effect in healthy animals but counteracted the changes in septic animals. The action of HMB was mediated by attenuation of proteasome activity and protein breakdown, not by stimulation of protein synthesis. More pronounced effect of the HMB treatment on myofibrillar proteolysis was observed in the SOL.

• MeSH
• časové faktory MeSH
• kathepsin B chemie   MeSH
• kathepsin L chemie   MeSH
• kosterní svaly účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kyslík chemie   MeSH
• leucin chemie   MeSH
• lyzozomy metabolismus   MeSH
• potkani Wistar MeSH
• proteasomový endopeptidasový komplex chemie   MeSH
• sepse farmakoterapie   metabolismus   MeSH
• valeráty farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• beta-hydroxyisovaleric acid MeSH Prohlížeč
• kathepsin B MeSH
• kathepsin L MeSH
• kyslík MeSH
• leucin MeSH
• proteasomový endopeptidasový komplex MeSH
• valeráty MeSH

Proteasome inhibitors are novel therapeutic agents for the treatment of cancer and other severe disorders. One of the possible side effects is influencing the metabolism of proteins. The aim of our study was to evaluate the influence of three proteasome inhibitors MG132, ZL(3)VS and AdaAhx(3)L(3)VS on protein metabolism and leucine oxidation in incubated skeletal muscle of control and septic rats. Total proteolysis was determined according to the rates of tyrosine release into the medium during incubation. The rates of protein synthesis and leucine oxidation were measured in a medium containing L-[1-(14)C]leucine. Protein synthesis was determined as the amount of L-[1-(14)C]leucine incorporated into proteins, and leucine oxidation was evaluated according to the release of (14)CO(2) during incubation. Sepsis was induced in rats by means of caecal ligation and puncture. MG132 reduced proteolysis by more than 50% and protein synthesis by 10-20% in the muscles of healthy rats. In septic rats, proteasome inhibitors, except ZL(3)VS, decreased proteolysis in both soleus and extensor digitorum longus (EDL) muscles, although none of the inhibitors had any effect on protein synthesis. Leucine oxidation was increased by AdaAhx(3)L(3)VS in the septic EDL muscle and decreased by MG132 in intact EDL muscle. We conclude that MG132 and AdaAhx(3)L(3)VS reversed protein catabolism in septic rat muscles.

• MeSH
• inhibitory cysteinových proteinas farmakologie   MeSH
• inhibitory proteasomu * MeSH
• játra účinky léků   metabolismus   MeSH
• kosterní svaly účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• ledviny účinky léků   metabolismus   MeSH
• leucin metabolismus   MeSH
• leupeptiny farmakologie   MeSH
• oligopeptidy farmakologie   MeSH
• oxidace-redukce účinky léků   MeSH
• potkani Wistar MeSH
• proteiny metabolismus   MeSH
• sepse metabolismus   MeSH
• slezina účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzyloxycarbonylleucyl-leucyl-leucine aldehyde MeSH Prohlížeč
• inhibitory cysteinových proteinas MeSH
• inhibitory proteasomu * MeSH
• leucin MeSH
• leupeptiny MeSH
• oligopeptidy MeSH
• proteiny MeSH

The aim of the present study was to evaluate the effect of short-term adrenergic blockade on the rate of whole-body protein turnover and leucine oxidation, and on protein synthesis in specific tissues in male rats. Adrenergic blockade was induced by guanethidine (100 mg/kg body weight subcutaneously). The control group was treated with saline. On the second day, the parameters of whole-body protein and leucine metabolism were evaluated using a primed constant intravenous infusion of L-[1-(14)C]leucine. Protein synthesis in tissues was determined on the basis of L-[1-(14)C]leucine incorporation. Guanethidine treatment caused a decrease in norepinephrine in skeletal muscle. Whole-body leucine oxidation and leucine oxidized fraction were higher in guanethidine-treated rats. There was an insignificant effect of guanethidine on whole-body proteolysis, protein synthesis and leucine clearance. However, protein balance was negative due to the larger difference between protein synthesis and proteolysis in guanethidine-treated animals compared to controls. In guanethidine-treated rats, protein synthesis was higher in the gastrocnemius muscle and in the kidneys and lower in liver and spleen. Changes in the small intestine and colon were insignificant. In addition, a marked decrease in concentration of several amino acids has been observed in the liver, the kidneys and the spleen. It is concluded that adrenergic blockade induced by guanethidine is associated with significant changes in protein metabolism, leucine oxidation and amino acid concentrations in several tissues. The most important consequences of treatment are considered to be a negative effect on protein balance, increased protein turnover in skeletal muscle and kidneys and decreased protein synthesis in the liver and spleen. These changes may also be induced by administration of other sympathetic blocking agents, e.g. in treatment of hypertension.

• MeSH
• adrenergní látky farmakologie   MeSH
• aminokyseliny analýza   MeSH
• guanethidin farmakologie   MeSH
• játra účinky léků   metabolismus   MeSH
• jejunum účinky léků   metabolismus   MeSH
• kolon účinky léků   metabolismus   MeSH
• kosterní svaly účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• ledviny účinky léků   metabolismus   MeSH
• leucin metabolismus   MeSH
• noradrenalin analýza   MeSH
• oxidace-redukce MeSH
• potkani Wistar MeSH
• proteiny metabolismus   MeSH
• slezina účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adrenergní látky MeSH
• aminokyseliny MeSH
• guanethidin MeSH
• leucin MeSH
• noradrenalin MeSH
• proteiny MeSH

Acidosis is frequently associated with protein wasting and derangements in amino acid metabolism. As its effect on protein metabolism is significantly modulated by other abnormal metabolic conditions caused by specific illnesses, it is difficult to separate out the effects on protein metabolism solely due to acidosis. The aim of the present study was to evaluate, using a model of isolated perfused rat liver, the direct response of hepatic tissue to acidosis. We have compared hepatic response to perfusion with a solution of pH 7.2 and 7.4 (controls). Parameters of protein and amino acid metabolism were measured using both recirculation and single-pass technique with 4,5-[3H]leucine, [1-14C]leucine and [1-14C]ketoisocaproate (ketoleucine) as tracers and on the basis of difference of amino acid levels in perfusion solution at the beginning and end of perfusion. In liver perfused with a solution of pH 7.2, we observed higher rates of proteolysis, protein synthesis, amino acid utilization and urea production. Furthermore, the liver perfused with a solution of pH 7.2 released a higher amount of proteins to perfusate than the liver perfused with a solution of pH 7.4. Enhanced decarboxylation of ketoisocaproate in liver perfused by a solution of a lower pH indicates increased catabolism of branched-chain amino acids (leucine, valine and isoleucine), decreased reamination of branched-chain keto acids to corresponding essential amino acids and increased ketogenesis from leucine.

• MeSH
• acidóza metabolismus   MeSH
• aminokyseliny metabolismus   MeSH
• játra metabolismus   MeSH
• koncentrace vodíkových iontů MeSH
• krysa rodu Rattus MeSH
• leucin metabolismus   MeSH
• orgánové kultury - kultivační techniky MeSH
• potkani Wistar MeSH
• proteiny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• leucin MeSH
• proteiny MeSH