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.     

Ammonia detoxification by accelerated oxidation of branched chain amino acids in brains of acute hepatic failure rats

BCAA aminotransferase and BCKA dehydrogenase activities are increased in the mitochondrial fractions from the brains of hepatic failure rats treated with two-thirds removal of CCl4-injured liver. Cerebral leucine decarboxylation was accelerated, and it well correlated with arterial blood ammonia levels. Elevation of brain ammonia content following an intraperitoneal injection of ammonium acetate to hepatic failure rats could be prevented by intravenous infusion of BCAA. Significantly increased brain glutamic acid, glutamine, and alanine contents were noted. These results suggested that accelerated brain BCAA catabolism in acute hepatic failure rats reduce the neurotoxicity of ammonia by promoting the synthesis of glutamic acid and glutamine from BCAA.     

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.     

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.     

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.     

Branched chain amino acids as source of specific branched chain volatile fatty acids during the fermentation process of fish sauce

Summary.  The source of the formation of branched chain volatile fatty acids (VFA) in fish sauce was investigated. Certain branched VFA were derived from the degradation of specific amino acids as iso-butyric acid from valine and iso-valeric acid from leucine. Short and long straight chain VFA were significantly higher in the linoleic acid added sample than in the control but did not significantly bring changes to the branched chain VFA. It is suggested that straight chain VFA developed from fish fats. Alanine and isoleucine did not have a clear influence on the production of volatile fatty acids. Received November 23, 2001 Accepted June 20, 2002 Published online December 18, 2002 RID="*" ID="*" Part of this paper was presented in the 7th International Congress on Amino Acids and Proteins in Vienna, Austria from August 6–10, 2001. Authors' address: Norlita G. Sanceda, Ph.D., Institute of Environmental Science for Human Life, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112, Japan, Fax: + 81-3-5978-5805, E-mail: lita@cc.ocha.ac.jp     

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.     

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.     

Uterine uptake of amino acids and placental glutamine--glutamate balance in the pregnant ewe

The uterine uptake of amino acids was studied in 10 pregnant sheep with gestational ages of 114-146 days. After recovery from surgery, arterial and uterine venous samples were drawn simultaneously via indwelling catheters and analysed for amino acid and oxygen content. In seven ewes, amino acid concentrations were measured by a chromatographic technique. In four ewes, glutamate and glutamine arterio-venous differences across the uterine and umbilical circulations were measured by an enzymatic method. The uptake of neutral and basic amino acids was 66 mumol/mmol O2 and 17.3 mumol/mmol O2, respectively. Comparison of uterine and umbilical uptake shows that the bulk of the neutral and basic amino acids taken up by the pregnant uterus are transferred to the fetus. there was no significant uptake of acidic amino acids (i.e. glutamate, aspartate and taurine). glutamate was delivered from the fetus to the placenta but excretion of glutamate into the uterine circulation was negligible. Glutamine and asparagine were delivered to the fetus in amount which were two to three times larger than the placental uptake of glutamate and aspartate. Therefore placental conversion of exogenous glutamate and aspartate to glutamine and asparagine cannot account entirely for the fetal uptake of these amino acids.     

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.