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PubMed2000

Oral administration of branched chain amino acids improves virus-induced glucose intolerance in mice.

We investigated the therapeutic effect of branched chain amino acids (BCAA) on mice with glucose intolerance induced by encephalomyocarditis virus (EMCV). Male DBA/2 mice were divided into three groups: treated with BCAA, (such as valine, leucine, and isoleucine), untreated, and control. BCAA-treated and -untreated groups were inoculated intraperitoneally with the NDK25 variant of EMCV at 200 plaque-forming units per mouse. The BCAA-treated group was administered orally 0.9 g/kg/day of each BCAA from the day after viral inoculation. The control group neither received virus inoculation nor was treated with BCAA. One week after inoculation, oral glucose tolerance tests (OGTT) were performed. After the glucose loading at 1.5 g/kg of body weight, blood glucose levels in the untreated group were 92.0+/-10.0 mg/dl at baseline, 224.6+/-10.9 mg/dl at 30 min, and 169.4+/-21.4 mg/dl at 60 min, which were significantly (P<0.05) higher than those in the control group (62. 7+/-3.6 mg/dl, 167.2+/-16.4, and 83.8+/-6.0 mg/dl, respectively). Blood glucose levels in the BCAA-treated group were 54.5+/-3.7 mg/dl at baseline, 145.2+/-8.7 mg/dl at 30 min, and 128.7+/-18.3 mg/dl at 60 min after the glucose loading, which were not significantly higher than those in the control group. Immunoreactive insulin levels at 30 min after the glucose loading were lower in the untreated group than in the control group at 1 week after virus inoculation. Histological investigations showed that the grade of insulitis in the pancreas of mice of the BCAA-treated group was lower than that of the mice of the untreated group. These results suggest that oral administration of BCAA is able to improve glucose intolerance induced by EMCV.

Administration, Oral↗
PubMed1987

Plasma clearances of branched-chain amino acids in control subjects and in patients with cirrhosis.

In an attempt to clarify the pathogenesis of the decreased branched-chain amino acid (BCAA) plasma concentrations in cirrhosis, the plasma clearances were measured in 7 patients with cirrhosis and in 7 age- and sex-matched control subjects. BCAA were given as prime-continuous infusions. The plasma clearances of valine, isoleucine, and leucine, calculated as infusion rate divided by steady state concentration, were low normal in cirrhotics despite hyperinsulinaemia, but different BCAA had different clearances (P less than 0.01). The endogenous basal appearance rates of BCAA, estimated by the basal concentrations multiplied by the plasma clearances, were lower in cirrhotics (P less than 0.025). The apparent theoretical volumes of distribution of BCAA, assessed by the ratio between the clearance and the concentration decay constant after infusion stop, were on average 67% of the total body weight, and were neither different among the three BCAA, nor between the two groups. The urea nitrogen synthesis rate did not increase significantly, suggesting that most of the infused BCAA nitrogen was taken up in peripheral tissues. The decreased concentration of BCAA in cirrhotics (394 +/- 81 mumol/l (mean +/- SD) in the present series vs 510 +/- 68 in controls; P less than 0.025) is not attributable to changes in plasma clearance. The most likely explanation is decreased afflux of BCAA into plasma.

Adult↗
PubMed1999

Abnormalities in branched-chain amino acid metabolism in cirrhosis: influence of hormonal and nutritional factors and directions for future research.

Plasma branched-chain amino acid (BCAA) levels are decreased in patients with liver cirrhosis, owing to an increase in BCAA tissue uptake and/or catabolism and a decrease in BCAA production from proteins. Non-specific factors such as malnutrition worsen this picture. Studies of BCAA fluxes and protein turnover in cirrhotic patients have given conflicting results due to patient heterogeneity, differences in method and bias in the expression of results. In well compensated cirrhosis, muscle wasting is moderate and probably due more to decreased protein synthesis than to increased protein catabolism. Hyperinsulinemia has been suggested as the main cause of decreased BCAA levels, by increasing BCAA uptake in muscle and additionally in adipose tissue. However, as depletion of fat stores is frequent in cirrhosis, this effect is certainly quantitatively weak. Also, there is no correlation between state of hyperinsulinemia and decrease in BCAA levels. An effect of cytokines (IL1 and TNF) on muscle BCAA catabolism is a possibility. Until recently, the contribution of the liver to abnormal BCAA metabolism has been underestimated. In cirrhotic liver an increase in liver transamination of branched-chain keto acids (BCKAs) has been suggested and may result from inhibition of liver BCKA dehydrogenase. A modification of protein turnover in cirrhotic liver must be also considered. Lastly, the contribution of non-hepatocyte liver cells, which are activated in cirrhosis, remains to be assessed.

Amino Acids, Branched-Chain↗
PubMedDate not supplied

Influence of ingesting a solution of branched-chain amino acids on plasma and muscle concentrations of amino acids during prolonged submaximal exercise.

On two occasions, seven male endurance-trained cyclists performed sustained exhaustive exercise with reduced muscle glycogen stores. During exercise, the subjects were supplied in random order with an aqueous solution of branched-chain amino acids (BCAA) or flavored water (placebo). Ingestion of BCAA caused the concentration of these amino acids to increase by 135% in the plasma and by 57% in muscle tissue during exercise, whereas in the placebo trial there was no change or a slight decrease in the concentration in plasma and a decrease of 18% in the muscle. The plasma concentration of alanine increased by 48% during exercise when BCAA were ingested, and the increase in the muscle concentration of alanine during exercise was larger (70% versus 31% in the placebo trial), suggesting an increased rate of alanine production. Also, the plasma concentration of arginine increased by 14% during exercise when BCAA were ingested, whereas there was no change during exercise in the placebo trial. There was a smaller decrease in the muscle glutamate concentration during exercise in the BCAA trial (32% versus 47% in the placebo trial; p < 0.05), but, for the remaining amino acids, there was no difference between the BCAA and placebo trials. There was a significant decrease in the muscle glycogen concentration during exercise in the placebo trial, whereas only a small decrease was found in the BCAA trial (28 and 9 mmol/kg wet wt [p < 0.05] in the placebo and BCAA trial, respectively). This might indicate that an increased supply of BCAA has a sparing effect on muscle glycogen degradation during exercise.

Adult↗
PubMed1999

Effects of branched-chain amino acids and carbohydrate on fatigue during intermittent, high-intensity running.

Experimental support for the hypothesized benefits of BCAA supplements on endurance performance is limited. However, it is theorized that the benefits may be enhanced if 1) BCAA are taken along with a pre-event carbohydrate meal as well as during exercise, and 2) the exercise is intermittent in nature. This study tested the effects of ingesting carbohydrate beverages with and without BCAA before and during intermittent high-intensity running to fatigue. Eight subjects performed 3 exercise trials consisting of intermittent shuttle running (walking, sprinting, and running) to fatigue. Subjects drank either carbohydrate drinks given 1 h before (5 mL/kg, 18% carbohydrate) and during exercise (2 mL/kg, 6% carbohydrate) (CHO), carbohydrate drinks with BCAA (7 g) added to the portions consumed 1 h before and immediately before exercise (CHO+BCAA), or flavored water placebos (P). Subjects ran longer when fed either CHO or CHO+BCAA as compared to P, with no differences between CHO and CHO+BCAA. CHO and CHO+BCAA also had higher plasma glucose and insulin, and lower FFA (p < 0.05). These findings confirm a beneficial effect of carbohydrate feedings on fatigue during exercise designed to mimic the activity pattern that occurs in sports like soccer, basketball, and hockey. They do not, however, support the hypothesis of an added benefit of BCAA supplements.

Adult↗
PubMed2005

Tolerance for branched-chain amino acids in experimental animals and humans.

There is no good evidence for establishing branched-chain amino acid (BCAA) tolerance levels for humans. With pigs, chicks, and rats, data are available concerning excessive intake levels of BCAA, but most of the information is for growing animals instead of for adults. Estimates of maintenance requirements for (high-quality) protein and BCAA in pigs weighing between 43 and 140 kg are 350 mg . kg(-1) . d(-1) for protein and 28.7 mg . kg(-1) . d(-1) for total BCAA. In contrast, human adult maintenance requirement estimates are much higher, i.e., 660 mg . kg(-1) . d(-1) for good quality protein and a range of 68 to 144 mg . kg(-1) . d(-1) for total BCAA. The human maintenance BCAA requirement estimates range from 10.3 to 22% of the maintenance protein requirement. Whole-body protein of 45-kg pigs contains 14.2 g BCAA/100 g protein, but the maintenance requirement (based on nitrogen balance) for total BCAA is only 8.2% of the total maintenance protein requirement. Conversely, sulfur amino acid (methionine + cysteine), threonine, and tryptophan maintenance requirements of pigs as a percentage of the maintenance protein requirement are much higher than whole-body protein levels of these amino acids. This suggests that the efficiency of using absorbed amino acids of dietary origin or of reusing endogenous amino acids arising from body protein catabolism may vary considerably among the indispensable amino acids. Additionally, work with pigs points to the conclusion that whole-body amino acid concentrations are poor predictors of both maintenance requirements and ideal amino acid profiles. Based on studies with young experimental animals, a rather large dietary excess (above requirement) of an individual BCAA is well tolerated when consumed in diets containing surfeit levels of protein and the other 2 BCAA.

Adult↗
PubMed2006

Branched-chain amino acids: enzyme and substrate regulation.

The three branched-chain amino acids (BCAAs) are the most hydrophobic of the amino acids and play crucial roles in determining the structures of globular proteins as well as the interaction of the transmembrane domains of membranous proteins with phospholipid bilayers. However, the three BCAAs do not behave identically. In terms of protein secondary structure, valine and isoleucine exhibit a definite preference for the beta-structure, whereas leucine has a higher preference for the alpha-helix. Although mutation of one BCAA to another is commonly regarded as conservative, there are well-documented examples of such substitutions that have a significant effect on protein function. The occurrence of BCAA in nature is, therefore, attributable to their primary role in protein structure, not to their secondary metabolic roles. These functions are important for almost all proteins; therefore, BCAA commonly account for approximately 20-25% of most dietary proteins. Dietary BCAA largely escape first-pass splanchnic metabolism. The first steps in their catabolism are common to all three, involving the BCAA aminotransferase (BCAT) and branched-chain alpha-keto acid dehydrogenase (BCKD). Their further metabolism employs distinct pathways to different end-products (glucose and/or ketone bodies). However, the fact that the flux-generating step for the catabolism of the three BCAAs occurs at one of the common steps indicates that the production of these downstream products are not individually regulated and, hence, may not play important individual roles. The catabolism of the BCAAs is highly regulated by both allosteric and covalent mechanisms. BCKD is inhibited by phosphorylation and activated by dephosphorylation. Allosteric inhibition of the kinase by the branched-chain keto acids (BCKA) (particularly by alpha-ketoisocaproate) serves both as a mechanism for promoting the catabolism of excess quantities of these amino acids as well as for conserving low concentrations of these dietary essential amino acids. Cytosolic and mitochondrial isoenzymes of BCAT have been identified. They are thought to play an important role in brain neurotransmitter metabolism.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2006

Modulations of muscle protein metabolism by branched-chain amino acids in normal and muscle-atrophying rats.

It has been shown that BCAAs, especially leucine, regulate skeletal muscle protein metabolism. However, it remains unclear how BCAAs regulate muscle protein metabolism and lead to anabolism in vivo. We examined muscle protein synthesis rate and breakdown rate simultaneously during BCAA infusion in muscle atrophy models as well as in normal healthy rats. Corticosterone-treated rats and hindlimb-immobilized rats were used as muscle atrophy models. Muscle protein synthesis rate and breakdown rate were measured as phenylalanine kinetics across the hindlimb. In anesthetized normal rats, BCAAs stimulated muscle protein synthesis despite low insulin concentration and did not suppress muscle protein breakdown. In corticosterone-treated rats, BCAAs failed to restore inhibited muscle protein synthesis, but reduced muscle protein breakdown. Immobilization of hindlimb increased muscle protein breakdown within a day. BCAAs did not change muscle protein metabolism, although essential amino acids (EAAs) suppressed muscle protein breakdown in hindlimb-immobilized rats. We also evaluated changes of fractional synthesis rate (FSR) of skeletal muscle protein during infusion of leucine alone or EAAs for 4 h in anesthetized normal rats. FSR showed a transient increase at 15-30 min of leucine infusion and then declined, whereas FSR stayed elevated throughout EAA infusion. We concluded that 1) BCAAs primarily stimulate muscle protein synthesis in normal rats independently of insulin; 2) EAAs are required to maintain the BCAA stimulation of muscle protein synthesis; and 3) The effects of BCAAs on muscle protein metabolism differ between atrophy models.

Amino Acids, Branched-Chain↗
PubMed2006

Application of branched-chain amino acids in human pathological states: renal failure.

During renal failure, abnormalities of BCAA and branched-chain keto acid (BCKA) metabolism are due to both the lack of renal contribution to amino acid metabolism and the impact of renal failure and acidosis on whole-body nitrogen metabolism. Abnormal BCAA and BCKA metabolism result in BCAA depletion as reflected by low plasma BCAAs and cellular valine. BCAA metabolic disturbances can alter tissue activities, particularly brain function, and nutritional status. In dialysis patients, BCAA oral supplementation can induce an improvement of appetite and nutritional status. During chronic renal failure, the aims of nutritional interventions are to minimize uremic toxicity, avoid malnutrition and delay progression of kidney disease. BCAA and BCKA supplements have been proposed to decrease further protein intake while maintaining satisfactory nutritional status. In this setting, BCAAs or BCKAs have not been administrated solely but in association with other essential AA or keto analogs. Therefore, the proper effects of BCAAs and/or BCKAs have not been studied separately. Protein restriction together with keto acids and/or essential AAs has been reported to improve insulin sensitivity and hyperparathyroidism and to be compatible with a preservation of nutritional status. Nonetheless, a careful monitoring of protein-calorie intake and nutritional status is needed. A recent meta-analysis concluded that reducing protein intake in patients with chronic renal failure reduces the occurrence of renal death by approximately 40% as compared with larger or unrestricted protein intake. The additional effect of essential amino acids and keto acids on retardation of progression of renal failure has not been demonstrated.

Amino Acids, Branched-Chain↗
PubMed2006

Assessment of branched-chain amino Acid status and potential for biomarkers.

BCAAs are not synthesized in the body in humans, but they are crucial in protein and neurotransmitter synthesis. The protein anabolic role of BCAAs seems to be mediated not only by their important role as a promoter of the translation process (and possibly acting at the transcription level) but also by inhibition of protein degradation. Leucine may play a critical role in these signaling pathways. Supplementation with BCAAs spares lean body mass during weight loss, promotes wound healing, may decrease muscle wasting with aging, and may have beneficial effects in renal and liver disease. BCAA supplementation is extensively used in the athletic field with the assumption of improved performance and muscle mass. Measuring serum BCAAs has limited clinical utility beyond the controlled setting because levels are affected by a variety of clinical states, and optimal levels in these scenarios have not been completely elucidated. We discuss the effects diet, hormones, stress, aging, and renal or liver dysfunction have on BCAA levels and how understanding the biological effects of BCAAs may help to develop biomarkers of BCAA status. We also discuss potential biomarkers of BCAA status.

Aging↗
PubMed2006

Nutraceutical effects of branched-chain amino acids on skeletal muscle.

BCAA catabolism in skeletal muscle is regulated by the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, located at the second step in the BCAA catabolic pathway. The activity of the BCKDH complex is regulated by a phosphorylation/dephosphorylation cycle. Almost all of BCKDH complex in skeletal muscle under normal and resting conditions is in an inactive/phosphorylated state, which may contribute to muscle protein synthesis and muscle growth. Exercise activates the muscle BCKDH complex, resulting in enhanced BCAA catabolism. Therefore, exercise may increase the BCAA requirement. It has been reported that BCAA supplementation before exercise attenuates the breakdown of muscle proteins during exercise in humans and that leucine strongly promotes protein synthesis in skeletal muscle in humans and rats, suggesting that a BCAA supplement may attenuate muscle damage induced by exercise and promote recovery from the damage. We have examined the effects of BCAA supplementation on delayed-onset muscle soreness (DOMS) and muscle fatigue induced by squat exercise in humans. The results obtained showed that BCAA supplementation prior to squat exercise decreased DOMS and muscle fatigue occurring for a few days after exercise. These findings suggest that BCAAs may be useful for muscle recovery following exercise.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1995

Effect of branched-chain amino acid and carbohydrate supplementation on the exercise-induced change in plasma and muscle concentration of amino acids in human subjects.

Five male endurance-trained subjects performed exhaustive exercise on a cycle ergometer at a work rate corresponding to 75% of their VO2max after reduction of their muscle glycogen stores. During exercise the subjects were given in random order a 6% carbohydrate solution continuing 7 g L-1 of branched-chain amino acids (BCAA), a 6% CHO solution and flavoured water. The physical performance was lowered in four of the five subjects when they were given flavoured water during exercise as compared with the two conditions when CHO was supplied. No difference in performance was found when the subjects were given CHO + BCAA or only CHO during exercise. When CHO + BCAA was supplied the plasma and muscle (vastus lateralis) concentrations of BCAA increased during exercise by 120 and 35%, respectively. In the other conditions there was no change or a slight decrease in the plasma concentrations of BCAA, but the muscle concentrations of BCAA were decreased after exercise. The plasma concentration of glutamine over the whole exercise period and 5 min after exercise was higher when CHO + BCAA were supplied during exercise compared with a supply of CHO alone or water. However, exercise caused no change in the muscle concentration of glutamine, whereas that of glutamate decreased in all three conditions. A supply of CHO + BCAA or CHO alone did not affect the exercise-induced increase in the plasma and muscle concentration of aromatic amino acids, indicating that neither BCAA nor CHO influenced the net protein degradation during exercise.

Administration, Oral↗
PubMed1989

Protective effect of branched chain-enriched amino acid formulation in myocardial ischemia.

The protective effect of a branched chain amino acid (BCAA) formulation on the ischemic myocardium was determined in four groups of passively perfused normothermic (37 C) isolated rat hearts perfused with Krebs-Henseleit (KH) or KH + BCAA. Time to ischemic contracture was significantly increased by the infusion of BCAA compared with KH (19.4 +/- 2.3 vs. 15.9 +/- 1.7 min). In a second set of experiments, rat hearts were perfused with KH or KH + BCAA solution followed by 2 min of glucose-free KH buffer. After 17 min of ischemia, both groups were reperfused for another 15 min. Percent of pressure recovery was significantly better with KH + BCAA (90.1 +/- 8.4) than with KH (56.4 +/- 40.0). Percent +dP/dt (time derivative of pressure at contraction) recovery was also significantly improved with KH + BCAA (96.5 +/- 26.9 vs. 58.1 +/- 44.0). Furthermore, arrhythmias were minimized by BCAA. There was no difference in change of coronary flow between these two groups. Thus, BCAAs appear to protect the heart against myocardial ischemic injury and to delay the time to ischemic contracture, particularly in the depleted ischemic heart. BCAAs enhance postischemic pressure recovery and improve postischemic systolic and diastolic myocardial function.

Amino Acids, Branched-Chain↗
PubMedDate not supplied

Is intravenous administration of branched chain amino acids effective in the treatment of hepatic encephalopathy? A multicenter study.

The influence of intravenous infusion of branched-chain amino acids (BCAAs) on brain function in patients with liver cirrhosis and acute hepatic encephalopathy was examined using a double-blind, randomized study design. Five medical centers in France and Sweden participated, and 50 patients were studied. The patients received either BCAAs (40 gm per day) in 5% glucose or 5% glucose alone (placebo) for 5 days or until "wake up". Nutritional support was provided with equal proportions of carbohydrate and fat. During BCAA administration, plasma concentrations of aromatic amino acids and methionine fell (20 to 40%, p less than 0.05 to 0.01), and the ratio of BCAAs to aromatic amino acid concentrations increased significantly. Clinical improvement was seen in 14 of 25 BCAA-treated patients and in 12 of 25 patients receiving placebo (N.S.). EEG responses were similar in the two groups during treatment. In the BCAA group, 10 of 25 patients died in the course of the study, compared to 5 of 25 in the placebo group (N.S.); six patients died from encephalopathy in the BCAA group as compared to three among placebo-treated patients. It is concluded that BCAA administration, in the dose and composition employed in the present study, reduces the concentrations of aromatic amino acids but neither improves cerebral function nor decreases mortality in patients with hepatic encephalopathy.

Acute Disease↗
PubMed1983

Branched-chain ketoacid dehydrogenase activity and growth of normal and mutant human fibroblasts: the effect of branched-chain amino acid concentration in culture medium.

We investigated changes in cell growth and branched chain ketoacid dehydrogenase (BCKD) activity by varying the concentrations of branched-chain amino acids (BCAAs) in culture medium of diploid fibroblasts from humans with normal BCKD and with impaired enzyme function. For logarithmic growth the two cell populations required similar minimal concentrations (0.05 mM) for each of leucine, isoleucine, and valine tested together. At confluency (saturation density) mutant cells grew less well to the extent of 30 to 40% in the highest concentrations of BCAAs that could be tested, 20.8 mM. BCKD activity was not changed by growth of normal or mutant cells in the absence of BCAAs. This enzyme activity was increased in normal but not mutant cells by growth in 20.8 mM BCAAs. These studies suggest the following: (1) BCKD mutant fibroblasts in culture slow their growth rate in response to high concentrations of BCAAs; (2) the growth disadvantage for mutant cells in high concentrations of BCAAs may be useful to select for enzyme normal hybrids derived when cells with two different mutations affecting BCKD are fused; (3) the increase of BCKD activity in normal but not mutant cells grown in high concentrations of BCAAs can distinguish these phenotypes more precisely in humans; and (4) the mechanism of BCKD stimulation in normal cells grown in high concentrations of BCAAs remains to be explained but can be pursued further with the cell culture conditions described.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1996

The antinociceptive effects of branched-chain amino acids: evidence for their ability to potentiate morphine analgesia.

The effect of branched-chain amino acids (BCAA) on pain threshold was studied in rats. Nociception was induced by the hot-plate analgesia meter, a method measuring supraspinally organized pain responses. After a single intravenous injection of BCAA (320 mg/kg), the percent change in latency time to the pain response significantly increased by 19% in 60 min, and by 22% in 75 min (p < 0.005), as compared to an injection of an equal volume of a standard concentration of an amino acid solution or physiological saline. Subsequently, we studied the interaction of BCAA with opioid-type analgesia. In combination with intravenously injected morphine (3 mg/kg), BCAA significantly potentiated and prolonged the action of morphine using the hot-plate test. From 5 min after morphine injection, the latencies to a pain response were markedly higher with the combination of BCAA and morphine (+80% and +89% at 5 min after morphine injection, if BCAA was administered 45 or 60 min prior to morphine injection, respectively) when compared with the effect of morphine alone (+13% at 5 min; p < 0.005). BCAA demonstrated analgesic effects, which, in combination with morphine, potentiated and prolonged the antinociceptive action of morphine. BCAA may represent a new adjunct treatment modality for acute and chronic pain, and give us further insight into the mechanisms of pain control.

Amino Acids, Branched-Chain↗
PubMed1995

Effects of anticonvulsant drug gabapentin on the enzymes in metabolic pathways of glutamate and GABA.

Gabapentin is a novel anticonvulsant drug. The anticonvulsant mechanism of gabapentin is not known. Based on the amino acid structure of gabapentin we explored its possible effects on glutamate and gamma-aminobutyric acid (GABA) metabolism in brain as they may relate to its anticonvulsant mechanisms of action. Gabapentin was tested for its effects on seven enzymes in the metabolic pathways of these two neurotransmitters: alanine aminotransferase (AL-T), aspartate aminotransferase (AS-T), GABA aminotransferase (GABA-T), branched-chain amino acid aminotransferase (BCAA-T), glutamine synthetase (Gln-S), glutaminase (GLNase), and glutamate dehydrogenase (GDH). In the presence of 10 mM gabapentin, only GABA-T, BCAA-T, and GDH activities were affected by this drug. Inhibition of GABA-T by gabapentin was weak (33%). The Ki values for inhibition of cytosolic and mitochondrial forms of GABA-T (17-20 mM) were much higher than the Km values for GABA (1.5-1.9 mM). It is, therefore, unlikely that inhibition of GABA-T by gabapentin is clinically relevant. As with leucine, gabapentin stimulated GDH activity. The GDH activity in rat brain synaptosomes was activated 6-fold and 3.4-fold, respectively, at saturating concentrations (10 mM) of leucine and gabapentin. The half-maximal stimulation by gabapentin was observed at approximately 1.5 mM. Gabapentin is not a substrate of BCAA-T, but it exhibited a potent competitive inhibition of both cytosolic and mitochondrial forms of brain BCAA-T. Inhibition of BCAA-T by this drug was reversible. The Ki values (0.8-1.4 mM) for inhibition of transamination by gabapentin were close to the apparent Km values for the branched-chain amino acids (BCAA) L-leucine, L-isoleucine, and L-valine (0.6-1.2 mM), suggesting that gabapentin may significantly reduce synthesis of glutamate from BCAA in brain by acting on BCAA-T.

Acetates↗
PubMed2004

Effect of oral supplementation with branched-chain amino acid granules in the early stage of cirrhosis.

Background/aims: We focus on branched-chain amino acid (BCAA) for patients with early stage of cirrhosis. We designed a randomized trial to examine whether increase or preservation of serum albumin levels was attained with administration BCAA granules for compensated cirrhosis, compared with decompensated cirrhosis. Patients and method: Sixty-five patients with HCV-related cirrhosis with serum albumin level less than 4.0g/dl were enrolled in this study. Half of the patients were randomly assigned to receive 14.22 g/day of BCAA granules orally, and half were assigned to a control group. Patients were evaluated at entry and at 1-year intervals for at least 2 years. We divided the parameters into three categories. Class 1 was decompensated cirrhosis with serum albumin level less than 3.5mg/dl. Class 2 was compensated cirrhosis with serum albumin level over 3.6 mg/dl and molar ratio of BCAA to tyrosine (BTR) less than 4. Class 3 was compensated cirrhosis with serum albumin level over 3.6 mg/dl and BTR over 4. Results: In class 1 and class 2, the BCAA group exhibited significantly higher rates of maintaining serum albumin level than the control group for 2 years. In contrast, there was no significant difference between the BCAA group and control group in rate of maintaining serum albumin levels in class 3. Conclusions: Those results suggested that if cirrhotic patients were in the compensated stage at the entry but with lower BTR, as for decompensated cirrhosis, oral BCAA supplementation might be effective in maintaining serum albumin. Stating appropriate nutritional interventions, such as supplementation of BCAA, in the early stage of cirrhosis may improve prognosis and maintain QOL.

Journal Article↗