Administration of branched-chain amino acids during sustained exercise--effects on performance and on plasma concentration of some amino acids.

Previous studies have shown that sustained exercise in human subjects causes an increase in the plasma concentration ratio of free tryptophan: other large neutral amino acids [including the branched-chain amino acids (BCAA)]. This should favour the transport of tryptophan into the brain and also the synthesis of 5-hydroxytryptamine, which is thought to contribute to fatigue during prolonged exercise. A mixture of the three BCAA was given to subjects during a 30-km cross-country race or a marathon (42.2 km) and the effects on mental and physical performances were measured. The mental performance, measured as the performance in the Stroop Colour and Word Test (CWT), was improved after, as compared to before the 30-km cross-country race when a BCAA supplement was given during the race, whereas the CWT scores were similar before and after in the placebo group. The running performance in the marathon was improved for the "slower" runners (3.05 h-3.30 h) when BCAA was taken during the race; however, there was no significant effect on the performance in the "faster" runners (less than 3.05 h). The results showed that both mental and physical performance was improved by an intake of BCAA during exercise. In addition, the effects of exercise on the plasma concentration of the aromatic amino acids were altered when a BCAA supplement was given during the marathon.     

Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines

Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge.     

Effects of carbohydrate feedings on plasma free tryptophan and branched-chain amino acids during prolonged cycling

Brain serotonin (5-hydroxytryptamine, 5-HT) has been suggested to be involved in central fatigue during prolonged exercise. Changes in the ratio of plasma free tryptophan (free Trp) to branched-chain amino acids (BCAA) are associated with altered brain 5-HT synthesis. The purposes of this study were to describe systematically the effects of prolonged exercise on changes in plasma free Trp and BCAA and to examine the effects of carbohydrate (CHO) feedings on these same variables. Eight well-trained men [VO2max = 57.8 (SE 4.1) ml kg-1 min-1] cycled for up to 255 min at a power output corresponding to VO2 at lactate threshold (approximately 68% VO2max) on three occasions separated by at least 1 week. Subjects drank 5 ml kg-1 body wt-1 of either a water placebo, or a liquid beverage containing a moderate (6% CHO) or high (12% CHO) concentration of carbohydrate beginning at min 14 of exercise and every 30 min thereafter. Exercise time to fatigue was shorter in subjects receiving placebo [190 (SE 4) min] as compared to 6% CHO [235 (SE 10) min] and 12% CHO [234 (SE 9) min] (P < 0.05). Glucose and insulin decreased in the placebo group, and free Trp, free-Trp/BCAA, and free fatty acids increased approximately five- to sevenfold (P < 0.05). These changes were attenuated in a dose-related manner by the carbohydrate drinks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Large neutral amino acids: dietary effects on brain neurochemistry and function

The ingestion of large neutral amino acids (LNAA), notably tryptophan, tyrosine and the branched-chain amino acids (BCAA), modifies tryptophan and tyrosine uptake into brain and their conversion to serotonin and catecholamines, respectively. The particular effect reflects the competitive nature of the transporter for LNAA at the blood–brain barrier. For example, raising blood tryptophan or tyrosine levels raises their uptake into brain, while raising blood BCAA levels lowers tryptophan and tyrosine uptake; serotonin and catecholamine synthesis in brain parallel the tryptophan and tyrosine changes. By changing blood LNAA levels, the ingestion of particular proteins causes surprisingly large variations in brain tryptophan uptake and serotonin synthesis, with minimal effects on tyrosine uptake and catecholamine synthesis. Such variations elicit predictable effects on mood, cognition and hormone secretion (prolactin, cortisol). The ingestion of mixtures of LNAA, particularly BCAA, lowers brain tryptophan uptake and serotonin synthesis. Though argued to improve physical performance by reducing serotonin function, such effects are generally considered modest at best. However, BCAA ingestion also lowers tyrosine uptake, and dopamine synthesis in brain. Increasing dopamine function in brain improves performance, suggesting that BCAA may fail to increase performance because dopamine is reduced. Conceivably, BCAA administered with tyrosine could prevent the decline in dopamine, while still eliciting a drop in serotonin. Such an LNAA mixture might thus prove an effective enhancer of physical performance. The thoughtful development and application of dietary proteins and LNAA mixtures may thus produce treatments with predictable and useful functional effects.     

Effect of acute and chronic exercise on plasma amino acids and prolactin concentrations and on [3H]ketanserin binding to serotonin2A receptors on human platelets

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been shown to modulate various physiological and psychological functions such as fatigue. Altered regulation of the serotonergic system has been suggested to play a role in response to exercise stress. In the present study, the influence was investigated of acute endurance exercise and short-term increase in the amount of training on the concentrations of the 5-HT precursor tryptophan (TRP), of prolactin (PRL) and of branched-chain amino acids (BCAA) in the blood, as well as on the binding of [3H]ketanserin to the serotonin-2A (5-HT2A) receptors on platelets. Nine healthy endurance-trained men were tested the day before (I) and after (II) a 9-day training programme. Samples of venous blood were drawn after an overnight fast and following 5 h of cycling. Fasted and post-exercise plasma concentrations of free TRP, BCAA and free TRP:BCAA ratio did not differ between I and II. A significant decrease of plasma BCAA (P < 0.01) and significant augmentations of plasma free TRP, free TRP:BCAA ratio and PRL (P < 0.01) were found post-exercise. The increase in plasma PRL was smaller in II compared with I. Acute endurance exercise reduced the density of platelet 5-HT2A receptor [3H]ketanserin binding sites at I and II (P < 0.05). The basal density of the binding sites and the affinity of [3H]ketanserin for these binding sites were unaffected by an increase in the amount of training. The present results support the hypothesis that acute endurance exercise may increase 5-HT availability. This was reflected in the periphery by increased concentration of the 5-HT precursor free TRP, by increased plasma PRL concentration, and by a reduction of 5-HT2A receptors on platelets. It remains to be resolved whether these alterations in the periphery occur in parallel with an increase in the availability of 5-HT in the brain.     

Influence of exercise on serotonergic neuromodulation in the brain

Summary. Implications of exercise on serotonergic neuromodulation in the brain have been investigated in two studies. Acute paroxetine (selective serotonin (5-HT) reuptake inhibitor) administration to endurance athletes, who performed a cycle ergometer test to exhaustion at moderate intensity, reduced time to exhaustion and post exercise cognitive performance in comparison to trials with placebo or BCAA administration. Furthermore, during a 3-week moderate endurance training of sedentary males basaline values of B_max of 5-HT transporters (5-HTT) and 5-HT_2A receptors (5-HT_2AR) on isolated platelet membranes increased while plasma prolactin (PRL) concentrations decreased as well as mood and physical efficiency improved. In contrast, after an excessive training program over four weeks, well-trained endurance athletes showed no change of B_max of 5-HTT, but a decline of 5-HT_2AR density and an increase in basal plasma PRL concentration. Mood was impaired and central fatigue increased. Thus, the impact of exercise on 5-HT neurotransmission may depend on training state of athletes and extent of exertion. The theoretical background of the implication of exercise and the effect of long lasting exhaustive exercise in athletes on mental and physical efficiency or central fatigue are evaluated. The significance of the primary disturbance of central neuromodulation and dysfunction of 5-HTT, 5-HT receptor subtypes and the phosphoinositol signal transduction as well as the limited modulation capacity of the 5-HT system in overstrain are also addressed. Received December 1, 1999 / Accepted February 1, 2000     

Effect of sustained exercise on concentrations of plasma aromatic and branched-chain amino acids and brain amines

In both trained and untrained rats, exercise increased the plasma concentration ratio of aromatic amino acids to branched-chain amino acids which might favour entry of the aromatic amino acids into the brain. Exercise in trained rats did not change the brain concentration of 5-hydroxytryptamine but increased that of 5-hydroxyindole acetic acid. Exercise in the untrained rat increased the concentration of brain tryptophan and that of 5-hydroxytryptamine but that of 5-hydroxyindole acetic acid was unchanged. The increased concentration of 5-hydroxytryptamine in untrained rats might be involved in central fatigue.     

Branched-Chain Amino Acids and Arginine Improve Performance in Two Consecutive Days of Simulated Handball Games in Male and Female Athletes: A Randomized Trial

The central nervous system plays a crucial role in the development of physical fatigue. The purpose of this study is to investigate the effect of combined supplementation of branched-chain amino acids (BCAA) and arginine on intermittent sprint performance in simulated handball games on 2 consecutive days. Methods: Fifteen male and seven female handball players consumed 0.17 g/kg BCAA and 0.04 g/kg arginine together (AA trial), or placebo (PB trial) before exercise. Each trial contained two 60-min simulated handball games on consecutive days. The game was consisted of 30 identical 2-min blocks and a 20 m all-out sprint was performed at the end of each block. The performance, measured by percentage changes of sprint time between day 1 and 2, was significantly better in the AA trial (first half: AA trial: -1.34±0.60%, PB trial: -0.21±0.69%; second half: AA trial: -1.68±0.58%, PB trial: 0.49±0.42%). The average ratings of perceive exertion throughout the 2-day trial was significantly lower in the AA trial (14.2±0.3) than the PB trial (15.1±0.4). Concurrently, post-exercise tryptophan/BCAA ratio on both days in the AA trial was significantly lower than the baseline. This study showed that BCAA and arginine supplementation could improve performance in intermittent sprints on the second consecutive day of simulated handball games in well-trained athletes by potentially alleviating central fatigue.     

Branched-chain amino acid supplementation and human performance when hypohydrated in the heat.

The serotonin system may contribute to reduced human performance when hypohydrated in the heat. This study determined whether branched-chain amino acid (BCAA) supplementation could sustain exercise and cognitive performance in the heat (40 degrees C dry bulb, 20% relative humidity) when hypohydrated by 4% of body mass. Seven heat-acclimated men completed two experimental trials, each consisting of one preparation and one test day. On day 1, a low-carbohydrate diet was eaten and subjects performed exhaustive cycling (morning) and treadmill exercise in the heat (afternoon) to lower muscle glycogen and achieve the desired hypohydration level. On day 2, subjects consumed an isocaloric BCAA and carbohydrate (BC) or carbohydrate-only drink during exercise. Experimental trials included 60 min of cycle ergometry (50% peak oxygen uptake) followed by a 30-min time trial in the heat. A cognitive test battery was completed before and after exercise, and blood samples were taken. BC produced a 2.5-fold increase (P < 0.05) in plasma BCAA and lowered (P < 0.05) the ratios of total tryptophan to BCAA and large neutral amino acid. Blood prolactin, glucose, lactate, and osmolality were not different between trials but increased over time. Cardiovascular and thermoregulatory data were also similar between trials. BC did not alter time-trial performance, cognitive performance, mood, perceived exertion, or perceived thermal comfort. We conclude that BCAA does not alter exercise or cognitive performance in the heat when subjects are hypohydrated.     

力竭运动及恢复期大鼠纹状体5-HT、DA及其代谢物浓度的动态变化研究

目的:观察一次性力竭运动过程及恢复期大鼠纹状体细胞外液中多巴胺(DA)和5-羟色胺(5-HT)及其代谢物浓度的动态变化规律。方法:采用活体微透析结合毛细管电泳-激光诱导技术,连续观察清醒大鼠在一次性力竭运动过程及恢复期纹状体细胞外液中酪氨酸(Tyr)、5-HT、5-羟吲哚乙酸(5-HIAA)、色氨酸(Trp)和DA浓度的动态变化。结果:大鼠纹状体细胞外液中Trp、5-HT、5-HIAA水平运动初期均未见显著变化(P>0.05),运动后期、力竭及恢复期均显著高于安静水平(P<0.05,P<0.01);DA、Tyr水平在运动后期、力竭及恢复期显著高于安静水平(P<0.05,P<0.01);DA/5-HT运动初期显著升高(P<0.05,P<0.01),运动后期出现下降趋势,力竭前15 min降至最低点,而恢复期略有回升,但运动后期、力竭及恢复期与安静状态相比均无显著差异。结论:力竭运动过程中大鼠纹状体细胞外液中DA和5-HT的动态变化具有阶段性特征,运动疲劳过程中状体内DA和5-HT两种神经递质的代谢水平均显著增强,而其中以5-HT的作用占优。     

Effects of acute tryptophan depletion on brain serotonin function and concentrations of dopamine and norepinephrine in C57BL/6J and BALB/cJ mice

Acute tryptophan depletion (ATD) is a method of lowering brain serotonin (5-HT). Administration of large neutral amino acids (LNAA) limits the transport of endogenous tryptophan (TRP) across the blood brain barrier by competition with other LNAAs and subsequently decreases serotonergic neurotransmission. A recent discussion on the specificity and efficacy of the ATD paradigm for inhibition of central nervous 5-HT has arisen. Moreover, side effects such as vomiting and nausea after intake of amino acids (AA) still limit its use. ATD Moja-De is a revised mixture of AAs which is less nauseating than conventional protocols. It has been used in preliminary clinical studies but its effects on central 5-HT mechanisms and other neurotransmitter systems have not been validated in an animal model. We tested ATD Moja-De (TRP-) in two strains of mice: C57BL/6J, and BALB/cJ, which are reported to have impaired 5-HT synthesis and a more anxious phenotype relative to other strains of mice. ATD Moja-De lowered brain TRP, significantly decreased 5-HT synthesis as indexed by 5-HTP levels after decarboxlyase inhibition, and lowered 5-HT and 5-HIAA in both strains of mice, however more so in C57BL/6J than in BALB/cJ. Dopamine and its metabolites as well as norepinephrine were not affected. A balanced (TRP+) control mixture did not raise 5-HT or 5-HIAA. The present findings suggest that ATD Moja-De effectively and specifically suppresses central serotonergic function. These results also demonstrate a strain-specific effect of ATD Moja-De on anxiety-like behavior.     

How does displacement of albumin-bound tryptophan cause sustained increases in the free tryptophan concentration in plasma and 5-hydroxytryptamine synthesis in brain?

Models of tryptophan catabolism and binding to serum albumin are presented to explain the observed effect of displacement of tryptophan from albumin on the concentrations of free and bound tryptophan and on the rate of 5-hydroxytryptamine (5-HT) synthesis from tryptophan in the brain. A rapid rate of dissociation of tryptophan from albumin (compared to the transit time of tryptophan through the liver) and a large fractional extraction of the free pool of tryptophan during passage through the liver are shown to be necessary factors in determining the effects observed. Because of the low fractional extraction of free tryptophan in the brain, the synthesis of 5-HT will be dependent only upon the free pool of tryptophan. Dissociation of tryptophan from albumin only causes a sustained increase in 5-HT synthesis in the brain because of the effect that this dissociation has on hepatic tryptophan catabolism and thereby on the free pool of tryptophan.     

Regulation of serotonin synthesis

The regulation of serotonin synthesis in the central nervous system seems to involve mechanisms which control the intracellular concentration of tryptophan and the hydroxylation step. Numerous situations are reviewed which demonstrate that changes in the concentration of free tryptophan in plasma and/or in the uptake of the amino acid in brain may alter tryptophan concentration and 5-HT synthesis. In other cases, modifications in 5-HT synthesis were still detected after tryptophan loading, clearly indicating that the tryptophan concentration is not the only critical parameter. In particular, changes in 5-HT synthesis dependent on nerve impulse flow seem to be regulated at the hydroxylation step. In addition, long term regulations of 5-HT synthesis involving changes in tryptophan hydroxylase concentration have been recently demonstrated. How serotoninergic neurons integrate all these regulating factors to modulate 5-HT synthesis is still an open question.     

Changes in plasma and brain tryptophan and brain serotonin and 5-hydroxyindoleacetic acid after footshock stress

Brain concentrations of tryptophan, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) and plasma amino acids were measured after 15 or 30 minutes of intermittent footshock. Footshock treatment significantly decreased the content of 5-HT in prefrontal cortex and hypothalamus, but not brainstem at 15 min, but the decreases were reversed by 30 min. 5-HIAA, the major catabolite of 5-HT, increased in prefrontal cortex after 15 min, and in prefrontal cortex and hypothalamus after 30 min footshock. 5-HIAA:5-HT ratios were increased at both timepoints in all three brain regions. Concomitant changes in the ratios of 3,4-dihydroxyphenylacetic acid (DOPAC) to dopamine and 3-methoxy,-4-hydroxyphenylethyleneglycol (MHPG) to norepinephrine were also observed. Brain concentrations of tryptophan increased progressively during the footshock in all three brain regions. Plasma concentrations of both tryptophan and tyrosine were also significantly increased, while those of histidine and lysine were decreased. It is possible that the stress-related changes in 5-HT metabolism are due to increased plasma tryptophan, in turn causing increased brain tryptophan and 5-HT synthesis. However, the transient decreases in 5-HT suggest a footshock-induced increase of 5-HT release, depleting existing stores of 5-HT, that are replenished by the increased systemic availability of tryptophan.     

Influence of a 36 h fast followed by refeeding with glucose, glycerol or placebo on metabolism and performance during prolonged exercise in man

Five men were studied during exercise to exhaustion on an electrically braked cycle ergometer at 70% of VO2max. The four experimental treatments were as follows: fasted for 36 h (A); fasted (36 h) and refed with glucose (B) or glycerol (C); postabsorptive (overnight fast, D). In B and C the subjects were given a drink containing glucose or glycerol (1g per kg body weight) 45 min before starting exercise. A placebo drink was given 45 min before exercise on treatments A and D. Despite an increased availability of circulating free fatty acids, beta-hydroxybutyrate and glycerol exercise time to exhaustion was significantly lower after fasting (treatment A 77.7 +/- 6.8 min) compared with treatment D (119.5 +/- 5.8 min). Refeeding with glucose or glycerol did not significantly improve performance (92.4 +/- 11.8 min and 80.8 +/- 3.6 min respectively) compared with treatment A and lowered circulating levels of FFA and beta-HB during exercise compared with A. Despite the probability of low liver glycogen levels after fasting, none of the subjects became hypoglycaemic (blood glucose less than 4 mmol.l-1) during exercise and their blood lactate concentrations were not high at exhaustion. Plasma levels of branched chain amino acids (BCAA) decreased progressively during exercise on treatments A, B and C and were considerably lower at exhaustion compared with treatment D. Falling plasma concentrations of BCAA during prolonged exercise may be implicated in the generation of central fatigue.     

力竭运动及恢复期大鼠纹状体5-HT、DA及其代谢物浓度的动态变化研究

目的：观察一次性力竭运动过程及恢复期大鼠纹状体细胞外液中多巴胺（DA）和5-羟色胺（5-HT）及其代谢物浓度的动态变化规律。方法：采用活体微透析结合毛细管电泳．激光诱导技术,连续观察清醒大鼠在一次性力竭运动过程及恢复期纹状体细胞外液中酪氨酸（Tyr）、5-HT、5-羟吲哚乙酸（5-HIAA）、色氨酸（Trp）和DA浓度的动态变化。结果：大鼠纹状体细胞外液中TW、5-HT、5-HIAA水平运动初期均未见显著变化（P〉0．05）,运动后期、力竭及恢复期均显著高于安静水平（P〈0．05,P〈0．01）;DA、Tyr水平在运动后期、力竭及恢复期显著高于安静水平（P〈0．05,P〈0．01）;DA／5-HT运动初期显著升高（P〈0．05,P〈0．01）,运动后期出现下降趋势,力竭前15min降至最低点。而恢复期略有回升,但运动后期、力竭及恢复期与安静状态相比均无显著差异。结论：力竭运动过程中大鼠纹状体细胞外液中DA和5-HT的动态变化具有阶段性特征,运动疲劳过程中状体内DA和5-HT两种神经递质的代谢水平均显著增强,而其中以5-HT的作用占优。     

Effects of insulin and streptozotocin-induced diabetes on brain tryptophan and serotonin metabolism in rats

Previous work by other authors has shown hat insulin administration increases brain tryptophan levels and serotonin (5–HT) metabolism. The present study partially replicates these results and tests whether these effects could be due to insulin-induced hypoglycemic stress, since stressers such as immobilization or food deprivation also increase brain tryptophan and 5-HT metabolism. Ingestion of a dextrose solution by rats administered insulin (2 I.U./kg) prevents the extreme fall in blood glucose concentration and rise in plasma corticosterone following insulin injections alone. This treatment, however, produces a larger increase in brain tryptophan (30%) than insulin-injected rats allowed only tap water. The greater accumulation of brain tryptophan may reflect an additive effect of the endogenously released insulin to that exogenously administered, since ingestion of the dextrose solution could trigger insulin secretion. In addition, brain tryptophan and 5-HT metabolism were measured in streptozotocin-diabetic rats maintained on several different feeding schedules to control for the effects of hyperphagia. All groups of diabetics showed significant decreases of approx 30% in brain tryptophan concentrations, while 5-HT metabolism was unchanged. This deficit in brain tryptophan is reversed within 2 h after insulin administration (2 I.U./kg). These results indicate that changes in brain tryptophan and 5-HT metabolism following insulin injections are not due to hypoglycemic stress, and that brain tryptophan is low in diabetics but increases above normal after administration of insulin. The results are discussed with respect to the effects of insulin on plasma levels of the neutral amino acids and a possible direct effect of insulin on the uptake of tryptophan by brain.     

Intake of branched-chain amino acids influences the levels of MAFbx mRNA and MuRF-1 total protein in resting and exercising human muscle

Resistance exercise and amino acids are two major factors that influence muscle protein turnover. Here, we examined the effects of resistance exercise and branched-chain amino acids (BCAA), individually and in combination, on the expression of anabolic and catabolic genes in human skeletal muscle. Seven subjects performed two sessions of unilateral leg press exercise with randomized supplementation with BCAA or flavored water. Biopsies were collected from the vastus lateralis muscle of both the resting and exercising legs before and repeatedly after exercise to determine levels of mRNA, protein phosphorylation, and amino acid concentrations. Intake of BCAA reduced (P < 0.05) MAFbx mRNA by 30 and 50% in the resting and exercising legs, respectively. The level of MuRF-1 mRNA was elevated (P < 0.05) in the exercising leg two- and threefold under the placebo and BCAA conditions, respectively, whereas MuRF-1 total protein increased by 20% (P < 0.05) only in the placebo condition. Phosphorylation of p70(S6k) increased to a larger extent (～2-fold; P < 0.05) in the early recovery period with BCAA supplementation, whereas the expression of genes regulating mTOR activity was not influenced by BCAA. Muscle levels of phenylalanine and tyrosine were reduced (13-17%) throughout recovery (P < 0.05) in the placebo condition and to a greater extent (32-43%; P < 0.05) following BCAA supplementation in both resting and exercising muscle. In conclusion, BCAA ingestion reduced MAFbx mRNA and prevented the exercise-induced increase in MuRF-1 total protein in both resting and exercising leg. Further-more, resistance exercise differently influenced MAFbx and MuRF-1 mRNA expression, suggesting both common and divergent regulation of these two ubiquitin ligases.     

Uncoupling protein-2 polymorphisms in type 2 diabetes,obesity, and insulin secretion

The aim of the study was to investigate the effect of resistance exercise alone or in combination with oral intake of branched-chain amino acids (BCAA) on phosphorylation of the 70-kDa S6 protein kinase (p70(S6k)) and mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK1/2), and p38 MAPK in skeletal muscle. Seven male subjects performed one session of quadriceps muscle resistance training (4 x 10 repetitions at 80% of one repetition maximum) on two occasions. In a randomized order, double-blind, crossover test, subjects ingested a solution of BCAA or placebo during and after exercise. Ingestion of BCAA increased plasma concentrations of isoleucine, leucine, and valine during exercise and throughout recovery after exercise (2 h postexercise), whereas no change was noted after the placebo trial. Resistance exercise led to a robust increase in p70(S6k) phosphorylation at Ser(424) and/or Thr(421), which persisted 1 and 2 h after exercise. BCAA ingestion further enhanced p70(S6k) phosphorylation 3.5-fold during recovery. p70(S6k) phosphorylation at Thr(389) was unaltered directly after resistance exercise. However, during recovery, Thr(389) phosphorylation was profoundly increased, but only during the BCAA trial. Furthermore, phosphorylation of the ribosomal protein S6 was also increased in the recovery period only during the BCAA trial. Exercise led to a marked increase in ERK1/2 and p38 MAPK phosphorylation, which was completely suppressed upon recovery and unaltered by BCAA. In conclusion, BCAA, ingested during and after resistance exercise, mediate signal transduction through p70(S6k) in skeletal muscle.     

STUDIES IN VIVO ON THE RELATIONSHIP BETWEEN BRAIN TRYPTOPHAN, BRAIN 5-HT SYNTHESIS AND HYPERACTIVITY IN RATS TREATED WITH A MONOAMINE OXIDASE INHIBITOR AND L-TRYPTOPHAN

Abstract— The effect of l -tryptophan loading upon the amount of 5-HT accumulating in the brains of rats pretreated with a monoamine oxidase inhibitor was studied. The amount of brain 5-HT accumulated increased with increasing tryptophan dosages and brain tryptophan concentrations up to a tryptophan dose of 120 mg/kg body wt. and a brain tryptophan of about 70 μg/g brain. Above this dose and concentration no further increase in brain 5-HT accumulation occurred. After monoamine oxidase inhibition and tryptophan loading gross hyperactivity and hyperpyrexia occurred. Monoamine oxidase inhibition, tryptophan administration and intact aromatic amino acid decarboxylase activity were all collectively essential for the production of hyperactivity and hyperpyrexia. DL-Parachlorophenyl-alanine prevented both the occurrence of hyperactivity and the increased accumulation of, brain 5-HT. Indices of hyperactivity correlated with the amount of brain 5-HT accumulating in 1 h after tryptophan loading but not with the overall concentration of brain 5-HT, suggesting that hyperactivity was dependent upon the rate of 5-HT synthesis. Reserpine and tetra-benazine pretreatment speeded the onset and rate of development of the hyperactive state without altering the synthesis of brain 5-HT. It is suggested that when monoamine oxidase is inhibited and the rate of 5-HT synthesis is increased, granular uptake and storage of 5-HT and other rate-limiting mechanisms for 5-HT inactivation are unable to prevent 5-HT 'spilling over’to produce hyperactivity. The crucial dependence of 5-HT synthesis upon brain tryptophan concentration and the ability of intraneuronal metabolism, when monoamine oxidase activity is intact, to cope with increased 5-HT synthesis and prevent ‘spillover’, raise the possibility that brain 5-HT synthesis is normally in excess of functional needs, and suggest that intraneuronal metabolism and the intraneuronal organization of 5-HT pools are of more importance than synthesis in regulating the amount of 5-HT available for functional activity.