Effects of dietary excesses of the branched-chain amino acids on growth, food intake and plasma amino acid concentrations of kittens

The effect of excesses of the branched-chain amino acids (BCAA), particularly leucine, on growth, food intake and plasma amino acid concentrations were investigated in kittens. Effects of excess leucine were tested in kittens fed five basal diets that varied in their nitrogen and amino acid contents. Compared to rats, kittens were much less sensitive to excesses of the BCAA. Addition of 10% leucine to basal diets that provided nitrogen just at or below the minimal requirement of kittens resulted in no change or increased growth and food intake of kittens when the isoleucine and valine concentrations in the basal diet were just at or slightly in excess of the kitten's minimal requirements for those amino acids. An adverse effect of leucine added to low nitrogen basal diets was observed only when isoleucine and valine were provided below the kitten's requirement (80% of requirement). When basal diets containing adequate nitrogen (24% amino acids) were tested, the addition of leucine (10%) resulted in an adverse effect when isoleucine and valine were provided at 80% of the kitten's requirement and in mild growth depressions when isoleucine and valine were provided at 1.1 times the requirement. Leucine-induced growth depression was alleviated by the addition of isoleucine and valine at 0.5%, indicating that excess leucine caused a BCAA antagonism or an amino acid imbalance. With the addition of leucine to the basal diets, there were consistent decreases in concentrations of alanine and tyrosine in plasma but no consistent depressions in the concentrations of isoleucine and valine.     

High levels of dietary amino and branched-chain alpha-keto acids alter plasma and brain amino acid concentrations in rats

Plasma and brain amino acid and plasma branched-chain alpha-keto acid (BCKA) concentrations were measured in rats fed diets containing high levels of individual amino and alpha-keto acids. Consumption of a low-protein (9% casein) diet high in leucine or alpha-ketoisocaproate depressed plasma concentrations of isoleucine and valine and their respective keto acids, alpha-keto-beta-methylvalerate and alpha-ketoisovalerate. High dietary levels of alpha-keto-beta-methylvalerate or alpha-ketoisovalerate (but not of isoleucine or valine) depressed plasma concentrations of the other BCKA and their respective branched-chain amino acids (BCAA). Consumption of a low protein, high phenylalanine diet depressed plasma concentrations of both BCAA and BCKA. Brain large neutral amino acid pools of rats fed all low-protein, high-amino acid diets were depleted. Consumption of diets high in individual BCKA increased brain concentrations of aromatic amino acids. In this study of rats allowed to feed for only 6 h/d, elevated brain phenylalanine concentration was associated with a significant depression of food intake, whereas elevated brain BCAA concentrations were not. Also, elevated plasma BCKA concentrations, comparable with those observed in maple syrup urine disease, were accompanied by elevations in concentrations of aromatic amino acids in brain but not in plasma.     

Effect of zinc deficiency on appetite and free amino acid concentrations in rat brain

Brain amino acids were measured in 30-day-old male Long-Evans rats subsequent to feeding a 20% egg white biotin-enriched zinc-deficient diet for 9 days. The zinc-deficient (ZD) group was given distilled deionized water. Zinc-supplemented control groups included pair-fed (PF), ad libitum-fed (AL) and ad libitum-fed, overnight fasted (OF) animals. Brain tyrosine concentrations and related amino acid ratios tended to be higher when food was consumed in all groups. Brain tryptophan concentrations and a brain amino acid ratio (glycine + serine + glutamine + taurine:leucine + isoleucine + valine + methionine) were not related to food intake in ZD rats in contrast to zinc-adequate controls. Also the brain ratio of tryptophan to the sum of large neutral amino acids minus tryptophan was not related to food intake in the ZD and AL-OF groups in contrast to the PF group. There were some differences in brain amino acid concentrations between ZD rats and the control groups; however, the pattern of the brain amino acids in ZD rats did not suggest that food intake was directly influenced by them.     

Branched-chain and other amino acids in tissues of rats fed leucine-limiting amino acid diets containing norleucine

Amino acid concentrations were measured in plasma, brain, muscle and liver from rats fed leucine-limiting diets containing varying proportions of other indispensable amino acids (IAA), the branched-chain amino acids (BCAA) and norleucine, a BCAA analog known to compete with large neutral amino acids (LNAA) for transport into tissues. Leucine was low and other IAA were high when dietary IAA were 125% and leucine was 65% of requirements; higher leucine and lower IAA concentrations occurred when dietary IAA were 75% of requirements. Tissue leucine was high and isoleucine and valine were low in rats fed excess leucine. Norleucine induced dose-dependent reductions in BCAA, especially in brain and muscle in which isoleucine or valine were sometimes undetectable. Leucine was not depressed further when control values were low as in the rats fed 125% IAA. Norleucine frequently prevented the high BCAA found after feeding additional BCAA. Other LNAA tended to be low in the brain and muscle of rats fed norleucine. Lysine was high only in the tissues of rats fed 75% IAA and norleucine; this effect was prevented when added leucine was given. Brain tryptophan, but not always serotonin, was low in rats fed norleucine. The results show transport-related, selective and usually marked depletions of tissue BCAA in rats fed norleucine; this suggests norleucine may be an aid in the treatment of clinical conditions involving excesses of BCAA.     

Leucine-induced amino acid antagonism in rats: muscle valine metabolism and growth impairment

The deleterious effects of branched-chain amino acid (BCAA) antagonism caused by excess dietary leucine include growth depression and subnormal valine and isoleucine pools. To investigate mechanisms causing these changes, rats were gavage-fed low-protein (9%) diets with or without BCAA supplements, and the metabolism of another BCAA (valine) was measured in incubated rat epitrochlearis muscles. A 10% leucine supplement (HL-10) inhibited growth; growth remained subnormal even when 2.6% isoleucine and 2.4% valine (HLIV-10) were added to the diet. Valine decarboxylation in muscle increased 170-270% in rats fed the HL-10 or HLIV-10 diets, but was still markedly lower than we previously found in muscle of rats fed a 14% protein diet. Valine incorporation into muscle protein as an estimate of protein synthesis was unaffected by any of the BCAA supplements. When a lower (4%) concentration of leucine (without or with 0.16% isoleucine and 0.16% valine) was studied, growth was also suppressed but only if rats had not been preconditioned to 9% protein. Although increased BCAA decarboxylation in muscle caused by excess dietary leucine contributes to low valine and isoleucine pools, abnormal growth appears to be independent of low valine and isoleucine levels and is not reflected in suppression of valine incorporation into muscle protein.     

Valine may be the first limiting branched-chain amino acid in egg protein in men

Recently, we defined an estimate for total branched-chain amino acids (BCAA) using the indicator amino acid oxidation technique in men fed the three BCAA (leucine, isoleucine and valine) in the proportion present in egg protein. Although egg protein is regarded as a high quality dietary protein source, it is not known whether the proportions of the three BCAA are optimal. Five men with known total BCAA requirements were restudied. Each men was studied with isoleucine, leucine or valine held constant at that individual's requirement level while the intake of the other two BCAA was reduced; one BCAA was held constant and the intake of the other two was reduced by 10 and 20% in random order. The label appearance from the oxidation of L-[13C]-phenylalanine to 13CO2 (F13CO2) in breath was monitored in response to the change in amino acid intake. When either isoleucine or leucine was held constant, and the other two BCAA reduced by 20% (valine and leucine, or valine and isoleucine, respectively) F13CO2 increased (P = 0.007, P = 0.038, respectively). We conclude that valine may be the first limiting BCAA in egg protein.     

高蛋白膳食对限食大鼠血清和肠粘膜氨基酸谱的影响

目的探讨高蛋白膳食对限食大鼠血清和肠粘膜氨基酸谱的影响。方法 Wistar雄性大鼠,按体重随机分成五组,分别为正常对照组,喂15%酪蛋白合成饲料,自由摄食;限食1组和2组分别按正常对照组摄食量的50%和30%对喂15%酪蛋白合成饲料;补蛋白1组和2组分别按正常对照组摄食量的50%和30%对喂30%酪蛋白合成饲料。实验2w后处死大鼠,取血和小肠组织检测游离氨基酸含量。结果限食组和补蛋白组的大鼠血清游离氨基酸浓度均低于正常对照组,并且除了甘氨酸和胱氨酸外均有统计学意义(P<0.05),其中苯丙氨酸、酪氨酸、亮氨酸、异亮氨酸、缬氨酸、谷氨酸下降最为明显(P<0.01);而补蛋白组的大鼠血清游离氨基酸浓度又高于相应的限食组,其中苯丙氨酸、酪氨酸、亮氨酸、异亮氨酸、缬氨酸、精氨酸、谷氨酸有显著性差异(P<0.05)。限食组和补蛋白组的大鼠肠粘膜游离氨基酸含量均低于正常对照组,其中苯丙氨酸、酪氨酸、亮氨酸、异亮氨酸、缬氨酸、精氨酸、谷氨酸有显著性差异(P<0.05);而补蛋白组的大鼠肠粘膜游离氨基酸含量又高于相应的限食组,其中亮氨酸、异亮氨酸、缬氨酸、精氨酸、谷氨酸有显著性差异(P<0.05)。结论提高膳食中的蛋白质比例能降低限食对大鼠血清和肠粘膜氨基酸谱的影响,改善血清氨基酸代谢。     

Influence of a low protein diet on brain contents of free amino acids and histamine in the weanling guinea pig

Male weanling guinea pigs fed ad libitum a 3 per cent protein diet for 21 days demonstrated marked reduction in plasma levels of essential amino acids when compared with control animals pair-fed normal protein diet. Most prominently affected were leucine(−70%), isoleucine (−69%), valine (−67%), threonine (−63%), phenylalanine (−54%) and lysine (−52%). Similar changes were noted in the liver. Plasma and liver contents of free histidine were resistant to malnutrition. Changes in brain levels of free amino acids were less extensive than in liver and plasma. Protein malnutrition produced a two-fold increase in brain content of free histidine, and associated with this were prominent elevations in levels of homocarnosine (+91%) and histamine (+161%). Several lines of evidence suggest some neuroregulatory roles for histamine and homocarnosine, and marked alterations in their levels may be one of the mechanisms by which protein-energy malnutrition elicits changes in behaviour and neuroendocrine function.     

Interactions among the branched-chain amino acids and their effects on methionine utilization in growing pigs: effects on nitrogen retention and amino acid utilization

An experiment was conducted to investigate the effects of branched-chain amino acid (BCAA) interactions on their utilization by growing pigs and the effects of excessive amounts of BCAA (leucine, isoleucine, valine) on the utilization of methionine. A semipurified diet containing 100 g crude protein/kg with a balanced amino acid pattern was prepared using casein supplemented with free amino acids. Three further diets were made by reducing the concentration of methionine + cyst(e)ine, valine or isoleucine by 20%. Each of these four diets was then supplemented with leucine (50% excess) or a mixture of BCAA (50% excess of each but excluding the limiting amino acid). All diets were isoenergetic and were made isonitrogenous by replacement of glutamic and aspartic acids. The twelve diets were given to twenty-four growing pigs (30-40 kg) in three periods according to a randomized block design. Each period lasted 8 d and N retention was measured during the last 5 d of each period. Reducing dietary methionine, valine or isoleucine reduced the utilization of N (N retained/N digested) by approximately 20% (P < 0.05). Adding leucine to the isoleucine-limiting diet decreased the utilization of N by 9% (P < 0.05). This was reversed by simultaneous addition of valine. Excess leucine in a valine-deficient diet did not significantly reduce N utilization. In methionine-limiting diets an excess of either leucine alone or of all three BCAA increased the utilization of N by 8% (P < 0.05).     

Comparative studies between rates of incorporation of branched-chain amino acids and their alpha-ketoanalogues into rat tissue proteins under different dietary conditions

Male albino rats (110-120 g) were fed for 10 days on an amino acid diet low in nitrogen (nitrogen = 1.05%) devoid of valine, leucine and isoleucine and supplemented with branched-chain alpha-ketoacids (9.4%) (BCKA-diet). Pair-fed controls received an isocaloric diet (AA-diet) which contained the three branched-chain amino acids (1.4%) instead of the alpha-ketoacids (nitrogen = 1.2%). A third group was fed on a standard diet. Measuring rates of incorporation of radioactive leucine, valine and their corresponding alpha-ketoacids into liver, kidney, heart and brain proteins of rats fed on a standard diet revealed that in liver, branched-chain alpha-ketoacids are incorporated to a lesser extent than the corresponding amino acids. The same was also observed with the BCKA-diet, while the AA-diet reduced BCAA incorporation with the consecutive improvement of the relative incorporation of BCKA over that of BCAA. Injection of branched-chain amino- and alpha-ketoacids results in equal rates of incorporation in kidney and heart proteins. Injecting branched-chain alpha-ketoacids leads to higher incorporation rates in brain than injecting branched-chain amino acids. Thus rates of incorporation of branched-chain alpha-ketoacids differ dependent on the tissue and on the diet applied. They are not consistent with those of branched-chain amino acids.     

Effect of dietary zinc deficiency on the endogenous phosphorylation and dephosphorylation of rat erythrocyte membrane

The effect of dietary zinc deficiency on patterns of phosphorylation and dephosphorylation of rat erythrocyte membrane proteins and erythrocyte filterability was examined. Weanling male Wistar rats were fed an egg white-based diet containing less than 1.1 mg zinc/kg diet ad libitum for 3 wk. Control rats were either pair-fed or ad libitum-fed the basal diet supplemented with 100 mg zinc/kg diet. Net phosphorylation and dephosphorylation of erythrocyte membrane proteins were carried out by an in vitro assay utilizing [gamma-32P]ATP. The membrane proteins were subsequently separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the 32P content of gel slices was counted by Cerenkov counting. Erythrocyte filterability was measured as the filtration time of suspensions of erythrocytes, both untreated and preincubated with diamide, under constant pressure. Erythrocyte ghosts from zinc-deficient rats demonstrated greater dephosphorylation of protein bands R1 plus R2 and R7 than pair-fed rats and greater net phosphorylation of band R2.2 than pair-fed or ad libitum-fed control rats (P less than 0.05). Erythrocytes from ad libitum-fed control rats showed significantly longer filtration times than those from zinc-deficient or pair-fed control rats. In conclusion, dietary zinc deficiency alters in vitro patterns of erythrocyte membrane protein phosphorylation and dephosphorylation, whereas the depression in food intake associated with the zinc deficiency increases erythrocyte filterability.     

Effect of dietary zinc deficiency and the associated drop in voluntary food intake on rat erythrocyte membrane polyamines

The effect of dietary zinc deficiency in the rat on the free (noncovalently bound) polyamine concentrations in erythrocyte membranes, in erythrocyte cytosol and in the blood plasma were determined. Weanling male Wistar rats were fed an egg white-based diet containing less than 1.0 mg Zn/kg diet for 3 wk ad libitum. Control rats were either pair-fed or ad libitum-fed the basal diet supplemented with 100 mg Zn/kg diet. Tissue fractions were extracted with 0.2 M perchloric acid and polyamines were measured in the soluble fraction by dansylation, thin-layer chromatography and fluorescence spectrophotometry of the isolated dansylated polyamines. The depressed food intake associated with dietary zinc deficiency caused significantly (P less than 0.05) lower plasma spermidine, erythrocyte cytosol putrescine, spermidine and spermine and erythrocyte membrane spermidine concentrations. In addition, the depressed food intake caused significantly lower spermidine-spermine ratios in the erythrocyte membrane and cytosol and in blood plasma. Dietary zinc deficiency per se caused significantly (P less than 0.05) higher plasma spermidine and spermine and erythrocyte membrane spermine concentrations and significantly lower spermidine-spermine ratios in erythrocyte membrane and cytosol than in pair-fed, zinc-adequate controls.     

Interactions among the branched-chain amino acids and their effects on methionine utilization in growing pigs: effects on plasma amino- and keto-acid concentrations and branched-chain keto-acid dehydrogenase activity

The present experiment was designed to elucidate the mechanism of the methionine-sparing effect of excess branched-chain amino acids (BCAA) reported in the previous paper (Langer & Fuller, 2000). Twelve growing gilts (30-35 kg) were prepared with arterial catheters. After recovery, they received for 7 d a semipurified diet with a balanced amino acid pattern. On the 7th day blood samples were taken before (16 h postabsorptive) and after the morning meal (4 h postprandial). The animals were then divided into three groups and received for a further 7 d a methionine-limiting diet (80% of requirement) (1) without any amino acid excess; (2) with excess leucine (50% over requirement); or (3) with excesses of all three BCAA (leucine, isoleucine, valine, each 50% over the requirement). On the 7th day blood samples were taken as in the first period, after which the animals were killed and liver and muscle samples taken. Plasma amino acid and branched-chain keto acid (BCKA) concentrations in the blood and branched-chain keto-acid dehydrogenase (BCKDH; EC 1.2.4.4) activity in liver and muscle homogenates were determined. Compared with those on the balanced diet, pigs fed on methionine-limiting diets had significantly lower (P < 0.05) plasma methionine concentrations in the postprandial but not in the postabsorptive state. There was no effect of either leucine or a mixture of all three BCAA fed in excess on plasma methionine concentrations. Excess dietary leucine reduced (P < 0.05) the plasma concentrations of isoleucine and valine in both the postprandial and postabsorptive states. Plasma concentrations of the BCKA reflected the changes in the corresponding amino acids. Basal BCKDH activity in the liver and total BCKDH activity in the biceps femoris muscle were significantly (P < 0.05) increased by excesses of leucine or all BCAA.     

Parenteral and enteral routes of feeding in neonatal piglets require different ratios of branched-chain amino acids

The requirements for total branched-chain amino acids (BCAA), isoleucine, leucine and valine, in neonatal piglets receiving parenteral and enteral nutrition was determined recently. The optimum ratio among BCAA during different routes of feeding is not yet known. In this study, the ratio of BCAA during parenteral and enteral feeding was tested using the indicator amino acid oxidation (IAAO) technique. Male Yorkshire piglets (n=24) received amino acid-based diets containing adequate nutrients for 5 d. Phenylalanine oxidation and kinetics were determined from a 4-h primed, constant infusion of L-[1-14C]-phenylalanine on d 6 and 8. On d 6, all piglets received a BCAA diet which met 75% of the total BCAA requirement, based on our previous research, with a ratio of 1:1.8:1.2 of isoleucine/leucine/valine. On d 8, the piglets were randomly assigned to receive one of the 3 test diets supplemented with isoleucine (+isoleucine), leucine (+leucine) or valine (+valine) to meet 100% of requirement, with the remaining two BCAA at 75% of requirement. The difference in phenylalanine oxidation (% of dose) between d 6 and 8 was used as an indicator of BCAA adequacy. In enterally fed piglets, the change in the percentage of the dose oxidized was minimal for all 3 test diets (mean=1.15%). In parenterally fed piglets, the difference in phenylalanine oxidation (% of dose) between d 6 and 8 was +isoleucine (12.6%), +leucine (2%) and +valine (6.6%). The ratio of 1:1.8:1.2 of isoleucine/leucine/valine is appropriate for enteral feeding, but during parenteral feeding, isoleucine was first limiting and valine was second limiting.     

Plasma levels of branched chain amino acids in patients on regular hemodialysis before and after including a high-protein supplement in their diet

Chronic renal failure (CRF) patients on hemodialysis have low plasma level of the branched chain amino acids (BCAA) leucine, isoleucine, and valine. The abnormalities in the plasma amino acid pool can be corrected with appropriate high-protein supplements. The present study was designed to evaluate the effect of a balanced protein nutritional supplement on the plasma level of BCAA. Twenty eight CRF patients who received hemodialysis treatment three times in a week were enrolled in the trial. The initial plasma levels of BCAA were as follows--leucine 15.46 +/- 3.88 mcg/ml, isoleucine 9.08 +/- 1.97 mcg/ml, and valine 24.05 +/- 5.06 mcg/ml. For a period of 6 months the patients received a balanced nutritional supplement (58-59% total protein content, leucine--8.6, isoleucine--4.8, and valine--5.7 g/100 g protein) on the day of hemodialysis at a dose 1.0 g/kg body weight. Three months after beginning of supplementation the plasma level of BCAA was found to be elevated--leucine by 36% (P < 0.001), valine by 30% (P < 0.001), and isoleucine by 27% (P < 0.001). The body mass index of the patients was also above the initial values. The plasma BCAA levels were maintained high until the sixth month from the beginning of trial and even a month after withdrawal of the supplement. The results obtained allow us to recommend inclusion of protein supplements with balanced amino acid content in the diet of these patients.     

Activation of liver branched-chain alpha-keto acid dehydrogenase in rats by excesses of dietary amino acids

As part of an effort to explain the leucine-induced depressions of plasma isoleucine and valine concentrations, and the concomitant stimulation of valine oxidation in vivo, branched-chain alpha-keto acid dehydrogenase (BCKAD) activity was measured in livers from rats that were fed for only 6 h/d large quantities of individual amino acids in a low protein diet. Preincubation of homogenates with buffer containing Mg2+ and Ca2+ allowed estimation of fully active complex. Cytosolic and mitochondrial branched-chain-amino-acid aminotransferase (BCAAT) activities were also measured in livers of rats fed an excess of leucine. The percentage of BCKAD in the active form in livers of rats fed the low protein diet containing an excess of leucine, isoleucine, valine or phenylalanine for 2 d was double that of rats fed the low protein control diet (control, leucine, isoleucine, valine and phenylalanine groups having, respectively, 45 +/- 2, 85 +/- 7, 85 +/- 3, 95 +/- 5, and 81 +/- 4% of hepatic BCKAD in the active form). Consumption of a low protein diet containing an excess of leucine had no significant effect on either cytosolic or mitochondrial BCAAT activities of liver. The response of BCKAD in liver can contribute to the leucine-induced stimulation of valine oxidation in vivo but analysis of the results of this study leads to the conclusion that other mechanisms, probably in nonhepatic tissues, must also be involved.     

Suppression of Endogenous Glucose Production by Isoleucine and Valine and Impact of Diet Composition

Leucine has been shown to acutely inhibit hepatic glucose production in rodents by a mechanism requiring its metabolism to acetyl-CoA in the mediobasal hypothalamus (MBH). In the early stages, all branched-chain amino acids (BCAA) are metabolized by a shared set of enzymes to produce a ketoacid, which is later metabolized to acetyl-CoA. Consequently, isoleucine and valine may also modulate glucose metabolism. To examine this possibility we performed intrahypothalamic infusions of isoleucine or valine in rats and assessed whole body glucose kinetics under basal conditions and during euglycemic pancreatic clamps. Furthermore, because high fat diet (HFD) consumption is known to interfere with central glucoregulation, we also asked whether the action of BCAAs was affected by HFD. We fed rats a lard-rich diet for a short interval and examined their response to central leucine. The results showed that both isoleucine and valine individually lowered blood glucose by decreasing liver glucose production. Furthermore, the action of the BCAA leucine was markedly attenuated by HFD feeding. We conclude that all three BCAAs centrally modulate glucose metabolism in the liver and that their action is disrupted by HFD-induced insulin resistance.     

Regulatory role of dietary leucine on plasma branched-chain amino acid levels in young men.

Four healthy young men were studied to explore the effects of dietary leucine intake on plasma levels of leucine,isoleucine and valine. Leucine-, valine-, leucine-valine-, and leucine-isoleucine-valine-free amino acid mixtures were studied during four-day experimental diet periods. The effects of giving amino acid mixtures with high-carbohydrate, low-fat or low-carbohydrate, high-fat diets were also studied. Deficient leucine intake increased plasma levels of valine and isoleucine, but a valine-free diet did not affect plasma levels of the other branched-chain amino acids. Leucine influence was evident during the postprandial and fasted phases. Valine and isoleucine levels were less markedly reduced when diets devoid of these amino acids were also leucine-free, as compared with a diet providing adequate leucine. Changes in the major dietary energy source failed to influence the qualitative effects of dietary leucine adequacy on the branched-chain amino acid levels in plasma. The results suggest that leucine facilitates both tissue uptake of branched-chain amino acids and their intracellular metabolism.     

Three targets of branched-chain amino acid supplementation in the treatment of liver disease

The article explains the pathogenesis of disturbances in branched-chain amino acid (BCAA; valine, leucine, and isoleucine) and protein metabolism in various forms of hepatic injury and it is suggested that the main cause of decrease in plasma BCAA concentration in liver cirrhosis is hyperammonemia. Three possible targets of BCAA supplementation in hepatic disease are suggested: (1) hepatic encephalopathy, (2) liver regeneration, and (3) hepatic cachexia. The BCAA may ameliorate hepatic encephalopathy by promoting ammonia detoxification, correction of the plasma amino acid imbalance, and by reduced brain influx of aromatic amino acids. The influence of BCAA supplementation on hepatic encephalopathy could be more effective in chronic hepatic injury with hyperammonemia and low concentrations of BCAA in blood than in acute hepatic illness, where hyperaminoacidemia frequently develops. The favorable effect of BCAA on liver regeneration and nutritional state of the body is related to their stimulatory effect on protein synthesis, secretion of hepatocyte growth factor, glutamine production and inhibitory effect on proteolysis. Presumably the beneficial effect of BCAA on hepatic cachexia is significant in compensated liver disease with decreased plasma BCAA concentrations, whereas it is less pronounced in hepatic diseases with inflammatory complications and enhanced protein turnover. It is concluded that specific benefits associated with BCAA supplementation depend significantly on the type of liver disease and on the presence of inflammatory reaction. An important task for clinical research is to identify groups of patients for whom BCAA treatment can significantly improve the health-related quality of life and the prognosis of hepatic disease.     

The branched-chain amino acid antagonism in chicks

The effects of dietary supplements of branched-chain amino acids on growth, food consumption and metabolism in chicks were investigated. When an adequate diet contained 1.20, 1.60, 2.25, 3.75, or 5.00% leucine, increasing leucine content caused reduced food consumption and weight gains, coupled with impaired efficiency of food utilization. When the diet deficient in branched-chain amino acids contained 0.98, 1.46, 2.25, 3.75, or 5.00% leucine, increasing leucine resulted in increased food consumption and reduced efficiency of food utilization when levels of leucine up to 3.75% were fed. Excess leucine depressed plasma concentrations of isoleucine and valine. Excesses of isoleucine or valine caused smaller depressions of concentrations of the other two branched-chain amino acids. All these effects were seen during the first 8 days of experiment, after which they diminished or disappeared. Muscle branched-chain amino acid aminotransferase (BCAT) (L-leucine:2-oxoglutarate aminotransferase, EC 2.6.1.6) activity was increased in chicks fed excess leucine but not in those fed excess isoleucine or valine. Hepatic alpha-ketoisocaproic dehydrogenase (KADH) (2-oxoisocaproate:lipoate oxidoreductase, EC 1.2.4.3) activity and muscle polyribosomal aggregation were unaffected by diet. When chicks were fed diets containing either 0.98 or 2.25% leucine, production of 14CO2 from [1-14C]isoleucine and [1-14C]valine was increased in chicks fed the higher level of leucine. The increase was small in both cases, representing approximately 2% of consumed isoleucine and valine. Increased production of 14CO2 was observed within 12 hours of feeding excess leucine; however, BCAT increased only after 2 to 4 days. No differences were seen in excreted 14C or in the relative distribution of 14C along the small intestine. We conclude that the chick is able to adapt in part to excesses of dietary leucine and that the branched-chain amino acid antagonism may involve increased catabolism of the limiting branched-chain amino acids.