Effect of branched chain amino acids on liver regeneration after partial hepatectomy

The authors investigated the effect of the enrichment of commercial amino acid solutions with branched chain amino acids on the development of liver regeneration. Partial (65-70%) hepatectomy was performed on male Wistar rats (140-160 g body weight). Starting with the day of the operation, amino acid solutions normally used in clinical practice and the same solutions enriched with branched chain amino acids were administered by stomach tube; 24, 48 and 96 h after the operation the animals were decapitated. The onset of DNA synthesis was found to be more rapid in animals given the enriched solutions. Once regeneration had started, the stimulant effect of an increased supply of branched chain amino acid on liver regeneration was smaller. Nevertheless, even in the later phase after partial hepatectomy branched chain amino acids had a stronger stimulant effect on liver regeneration after partial hepatectomy than an energy supply in the form of sorbitol.     

The effect of branched chain amino acids on protein synthesis in two skeletal muscles of Japanese quail.

Two different isolated skeletal muscles of Japanese quail were used. The influence of branched chain amino acids on the fractional rate of protein synthesis (FSR) was evaluated using 14C-tyrosine. The addition of 0.5 mM valine, leucine or isoleucine to the incubation medium significantly decreased (P<0.05) the value of FSR in extensor metacarpalis radialis. In the ambiens muscle only the application of leucine increased the FSR significantly while valine and isoleucine were without any effect.     

Fermentative production of branched chain amino acids: a focus on metabolic engineering

The branched chain amino acids (BCAAs), l-valine, l-leucine, and l-isoleucine, have recently been attracting much attention as their potential to be applied in various fields, including animal feed additive, cosmetics, and pharmaceuticals, increased. Strategies for developing microbial strains efficiently producing BCAAs are now in transition toward systems metabolic engineering from random mutagenesis. The metabolism and regulatory circuits of BCAA biosynthesis need to be thoroughly understood for designing system-wide metabolic engineering strategies. Here we review the current knowledge on BCAAs including their biosynthetic pathways, regulations, and export and transport systems. Recent advances in the development of BCAA production strains are also reviewed with a particular focus on l-valine production strain. At the end, the general strategies for developing BCAA overproducers by systems metabolic engineering are suggested.     

骨骼肌支链氨基酸代谢小分子与运动

骨骼肌是支链氨基酸的主要代谢场所,其代谢产生的分支α-酮酸,C3、C4和C5酰基肉碱,3-羟基异丁酸以及β-氨基异丁酸等代谢小分子,具有代谢和信号分子的双重身份,不仅作用于骨骼肌自身,还可进入血液循环,作用于脂肪、心肌、肝脏等外周组织,调节机体稳态。运动与支链氨基酸代谢关系密切,随着代谢组学的发展,运动与支链氨基酸代谢小分子的研究必将成为新的热点。本文将对上述支链氨基酸代谢小分子代谢过程、生物学功能及病理生理意义及运动对它们影响的研究进展进行综述。     

Protective effect of branched chain amino acids on hindlimb suspension-induced muscle atrophy in growing rats

Purpose

The effect of BCAA (branched chain amino acid) administration on muscle atrophy during growth phases is not well known. We investigated whether BCAA administration can prevent the muscle atrophy induced by hindlimb suspension in growing male rats.

Methods

Male Wistar rats were assigned to 1 of 2 groups (n = 7/group): hindlimb suspension and hindlimb suspension with oral BCAA administration (600 mg·kg⁻¹·day⁻¹, valine 1: leucine 2: isoleucine 1). After 14 days of hindlimb suspension, the weight and mRNA levels of the soleus muscle were measured.

Results

BCAA administration prevented a decrease in soleus muscle weight. BCAA administration attenuated atrogin-1 and MuRF1 mRNA expression, which has been reported to play a pivotal role in muscle atrophy.

Conclusion

BCAA could serve as an effective supplement for the prevention or treatment of muscle atrophy, especially atrophy caused by weightlessness.     

Elevation of transamination of branched chain amino acids in brain in acute ammonia toxicity

The activity levels of leucine, isoleucine and valine aminotransferases were determined in various cerebral regions, liver and muscle of rats injected with a large dose of ammonium acetate and were compared with those of normal animals. In brain the activity levels of both leucine and isoleucine aminotransferases were elevated in both preconvulsive and convulsive states. Valine aminotransferase activity was suppressed in brain stem and corpus striatum and was elevated in cerebellum and hippocampus in preconvulsive states. During convulsions its activity was suppressed in cerebral cortex and hippocampus. Under these conditions, there was a suppression of both leucine and valine aminotransferases in muscle. In liver, however, the activities of these enzymes were elevated. The results suggested that the glutamate required for glutamine formation in hyperammonaemic states in brain might be obtained from branched chain amino acids, especially leucine and isoleucine.     

In vitro effect of branched chain amino acids on the ribosomal cycle in muscles of fasted rats.

1) The effect of a single i.p injection of branched chain amino acids on ribosomal profiles of psoas muscles was studied in rats after a 48--96 hour fast. Experimental and control animals received glucose and insulin 1--2 hours before killing. 2) The ratio of polysomes to subunits and monomers decreased progressively during the fast. 3) The administration of the three branched chain amino acids together or leucine alone significantly increased the proportion of polysomes. 4) This effect was not observed in rats fed ad libitum. 5) It is suggested that the branched chain amino acids and specifically leucine may be required for the full protein anabolic response of muscles to insulin during a prolonged fast.     

Effect of the composition of branched chain amino acids, taurine, and tryptophan on the amino acid metabolism in experimental models of alcoholism

Ethanol withdrawal after forced alcoholization of rats according to Majchrowicz led to the development of amino acid imbalance in the pool of free amino acids in the liver (increasing levels of alanine, aspartate, glutamate, glutamine and histidine, decreasing levels of glycine, lysine, threonine and taurine) and blood plasma (increasing levels of tyrosine and alanine, decreasing levels of most glycogen aminoacids, branched-chain aminoacids and Lys). Less profound changes were observed after prolonged alcohol intoxication (decreasing levels of alanine, ornitine, citrulline and increasing level of Glu in liver, increasing levels of sulfur-containing compounds, Asp and Lys in blood plasma). Amino acid mixture which contained branched-chain amino acids, taurine and tryptophan administered intragastrically was found to correct levels of sulfur-containing amino acids, threonine, lysine and isoleucine after ethanol withdrawal and to eliminate disorders in urea cycle, exchange of threonine, glycine and phenylalanine after prolonged alcohol intoxication.     

Effects of insulin, glucose, and amino acids on protein turnover in rat diaphragm.

A simple method is described for measuring rates of protein synthesis and degradation in isolated rat diaphragm. Muscles incubated in Krebs-Ringer bicarbonate buffer showed a linear rate of synthesis for 3 hours. At the same time, the muscle released tyrosine and ninhydrin-positive material, primarily amino acids, at a linear rate. This release was not a nonspecific leakage of material from the intracellular pools, but reflected net protein degradation. Tyrosine was chosen for studies of protein turnover, since it rapidly equilibrates between intracellular pools and the medium, it can be measured fluorometrically, and it is neither synthesized nor degraded by this tissue. To follow protein degradation independently of synthesis, muscles were incubated in the presence of cycloheximide. Under these conditions, the amount of tyrosine in the intracellular pools was constant, while the muscle released tyrosine at a linear rate. This tyrosine release was used as a measure of degradation. This preparation was used to study the influence of various factors known to be important for muscle growth on protein synthesis and degradation. Similar effects were obtained with diaphragms of normal and fasted rats although the latter showed decreased synthesis and increased protein degradation. Insulin by itself not only stimulated synthesis but also inhibited protein degradation (even in the presence of cycloheximide). These two effects served to reduce the net release of tyrosine from muscle protein to comparable extents. Effects of insulin on synthesis and degradation were greater when glucose was also present in the medium. Glucose by itself inhibited protein degradation but in the absence of insulin glucose had no significant effect on synthesis. Nevertheless, glucose stimulated incorporation of radioactivive tyrosine into protein, but this effect was due to an increased intracellular specific activity. Unlike glucose neither beta-hydroxybutyrate or octanoic acid had any demonstrable effects on protein degradion. The addition of amino acids at plasma concentrations both promoted protein synthesis and inhibited degradation in the diaphragm. Five times normal plasma concentrations of the amino acids had larger effects. The three branched chain amino acids together stimulated synthesis and reduced degradation, while the remaining plasma amino acids did not affect either process significantly. Thus leucine, isoleucine, and valine appear responsible for the effects of plasma amino or isoleucine and valine together, also were able to inhibit protein degradation and promote synthesis.     

Significance of branched chain amino acids as possible stimulators of hepatocyte growth factor

Amino acids can serve as regulatory molecules that modulate numerous cellular functions. Branched chain amino acids (BCAAs) are known to exert influences on cellular metabolism, amino acid transport, protein turn over, and gene expression. However, the mechanisms involved in the specific effect of BCAAs have not been clarified. BCAA supplementation therapy is a current treatment for patients with liver cirrhosis, therefore, specific BCAA activities should be examined. Hepatocyte growth factor (HGF) is considered to be a pleiotropic factor, and is reported to modulate gene expression and to stimulate the proliferation and functions of many cell types, including hepatocytes. A potential application of HGF for several types of diseases has been postulated. Here, we describe the potential of BCAAs as a therapeutic agent that acts through the induction of HGF production in the liver.     

Measurement of branched chain amino acids in blood plasma by high performance liquid chromatography

A simple and rapid high performance liquid chromatographic technique is described for the separation and quantitation of plasma branched chain amino acids. After addition of a norleucine internal standard, plasma samples are acidified with acetic acid, and amino acids are separated from proteins and other plasma components by passage of the acidified plasma through an ion exchange resin. The ammonium hydroxide eluate from the resin is dried, phenylisothiocyanate derivatives are prepared, and the amino acids are separated on a Waters reverse-phase "Pico-Tag" column with an ultraviolet detector set at 254 nm. In addition to the branched chain amino acids (leucine, valine, and isoleucine), aspartate, glutamate, serine, threonine, alanine, and methionine are quantitated with high precision and accuracy, as verified by quantitative recovery and comparison with an automatic amino acid analyzer. The advantages of the method are its simplicity, speed, stability of derivatives, high reproducibility, low per-sample cost, and the use of a simple fixed-wavelength ultraviolet detector.