ESSENTIAL AA AND BCAA
Amino acids are organic compounds which contain both an amino group and a carboxyl group. The human body can synthesize all of the amino acids necessary to build proteins except for the ten called the "essential amino acids": Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tyrptophan, Valine.
The amino acids arginine, methionine and phenylalanine are considered essential for reasons not directly related to lack of synthesis. Arginine is synthesized by mammalian cells but at a rate that is insufficient to meet the growth needs of the body and the majority that is synthesized is cleaved to form urea. Methionine is required in large amounts to produce cysteine if the latter amino acid is not adequately supplied in the diet. Similarly, phenylalanine is needed in large amounts to form tyrosine if the latter is not adequately supplied in the diet.
An adequate diet must contain these essential amino acids. Typically, they are supplied by meat and dairy products. They can be supplied by a combination of cereal grains and legumes.
Leucine, Isoleucine, and Valine : Branched-chain Amino Acids (BCAA)
This group of essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet.
Leucine, isoleucine, and valine are among the most hydrophobic of amino acids. This is a crucial determinant of their role in globular proteins, membranous proteins, and coiled-coil structures. Generally, the interior of water-soluble globular proteins consists, largely, of hydrophobic amino acids, principally leucine, isoleucine, valine, phenylalanine, and methionine. This is important, not only for the stability of the folded protein, but also for the folding pathway that leads to the mature structure (Principles of protein folding--a perspective from simple exact models..1993). It is also important for the function of some globular proteins; for example, the hydrophobic residues create a nonaqueous environment that is important for oxygen binding in myoglobin and hemoglobin, and for substrate binding and catalysis in a variety of enzymes(Dominant forces in protein folding..1990). A few globular proteins are not water soluble, but lipid soluble. For example, lung surfactant protein B must interact with phospholipids in surfactant, so it is among the most hydrophobic of proteins (Structural and functional role of leucine residues in proteins..1973).BCAAs make up 37% of the amino acid composition of surfactant protein B (17.7% leucine, 11.4% valine, 7.6% isoleucine). The dominant structural feature of this protein is its amphipathic helices, with the branched-chain residues interacting with lipid acyl chains, and positively charged groups interacting with the lipid head groups. Membranous proteins require hydrophobic amino acids in their transmembrane domains for interaction with the hydrocarbon chains of fatty acids.(Primary structure of human erythrocyte glycophorin A. Isolation and characterization of peptides and complete amino acid sequence..1978)
Another important role of leucine and its hydrophobic partners occurs in coiled-coiled α-helices in such proteins as myosin, fibrinogen, keratin, and a number of transcription factors. Each polypeptide of the rod-like coiled coil has an amino acid sequence containing a number of heptad repeats, with leucine often in the fourth position, and another hydrophobic residue in the first position.(Extended knobs-into-holes packing in classical and complex coiled-coil assemblies...2003).
In transcription factors, coiled coils, referred to as leucine zippers, permit formation of homodimers and/or heterodimers, which are the functionally active form of such transcription factors as Fos and Jun.(Branched-Chain Amino Acids: Enzyme and Substrate Regulation..2006)
Despite their similarity, the three BCAAs play subtly different roles in proteins. Their side chains differ in size, shape, and hydrophobicity. Therefore, they have different predilections for different secondary structure motifs. Leucine is more common in a-helices than in b-sheets, whereas the reverse is true for valine and isoleucine. These preferences account for the key role of leucine in helical zipper structures. The differences also account for the fact that these amino acids are not always interchangeable in proteins.(Empirical predictions of protein conformation..1978). There are, of course, many occasions when such substitutions are conservative but this is not invariable. For example, a substitution of isoleucine for valine in transthyretin results in a cardiomyopathy characterized by amyloid deposition in the heart (The V122I cardiomyopathy variant of transthyretin increases the velocity of rate-limiting tetramer dissociation, resulting in accelerated amyloidosis..2001). A valine for leucine substitution in the peroxisome proliferator-activated receptor-a results in an altered plasma lipid profile (The peroxisome proliferator- activated receptor-a Leu 162 Val polymorphism influences the metabolic response to a dietary intervention altering fatty acid proportions in normal men..2005) whereas a leucine for valine substitution in the extracellular calcium receptor of the TM6/TM7 protein leads to autosomal dominant hypocalciuria ("A region in the seven-transmembrane domain of the human Ca21 receptor critical for response to Ca21..2005" :http://www.jbc.org/content/280/6/5113.abstract?ijkey=9d6d923f6befc2e0b4977e1fe34af4c5f0dc03bb&keytype2=tf_ipsecsha).
All three of the BCAAs are readily produced under conditions designed to mimic prebiotic organic synthesis(Weber et al. 1981). They have been retained because of their critical roles in protein structure. Most proteins have a relatively high proportion of these amino acids. Indeed, most dietary proteins consist of 20% BCAAs. They comprise some 35% of the indispensible amino acid requirements of mammals Branched-chain amino acid metabolism..1984).
METABOLIC DISPOSAL OF THE BCAAS
Unusual aspects of BCAA metabolism.
BCAA metabolism is characterized by a number of unusual features. First, although these amino acids play a number of regulatory roles (e.g., in muscle protein synthesis, insulin secretion, and brain amino acid uptake), they are not metabolized to unique biologically active molecules. Second, their catabolism involves two common steps and, indeed, the flux-generating step, branched chain keto acid dehydrogenase (BCKD)5, is a common step; therefore, BCAAs tend to be catabolized in lockstep. Third, dietary BCAAs largely escape first-pass hepatic catabolism.( Regulation of branched-chain amino acid catabolism: nutritional and hormonal regulation of the expression of the branched-chain a-keto acid dehydrogenase kinase..2001).
One of the distinguishing features of BCAA catabolism is the relatively small fraction of the capacity that resides in the liver,(all tissues have some capability for synthesis of the non essential amino acids, amino acid remodeling, and conversion of non-amino acid carbon skeletons into amino acids and other derivatives that contain nitrogen.
However, the liver is the major site of nitrogen metabolism in the body).
About half of the capacity of BCAA metabolism resides in skeletal muscle, whereas a considerable portion of the activity also resides in adipose tissue. These results are only suggestive because other factors such as rates of blood flow, and transport into cells, are also important. Nevertheless, they are consistent with a body of experimental evidence. After ingestion of a protein-rich meal the three BCAAs accounted for >50% of the splanchnic output of amino acids even though they only comprise 20% of the protein source (beef) that was ingested. Clearly, they largely escaped splanchnic catabolism. After ingestion of a steak it was observed a marked increased in BCAA uptake into muscle, but only a minor increase in BCKA output. Clearly, muscle is a major site for BCAA catabolism.(Effect of protein ingestion on splanchnic and leg metabolism in normal man and in patients with diabetes mellitus..1976).
Liver contains the urea cycle as well as the catabolic enzymes for most of the amino acids. However, it is now apparent that the textbook statement that liver oxidizes most of the dietary amino acids cannot be true.(Quantitative analysis of amino acid oxidation and related gluconeogenesis in humans..1992).(Catabolism Dominates the First-Pass Intestinal Metabolism of Dietary Essential Amino Acids in Milk Protein-Fed Piglets..1998). First, the liver does not completely oxidize many amino acids but converts them to glucose and acetoacetate, even in the fed state. Second, a considerable portion of dietary amino acids are metabolized extra hepatically, including the appreciable first-pass intestinal metabolism of many amino acids and the muscle catabolism of the BCAAs.(Interorgan metabolism of amino acids in streptozotocin-diabetic ketoacidotic rat..
The second unusual feature of BCAA metabolism is that the first two enzymes of their catabolic disposal, the aminotransferase and the flux generating dehydrogenase, are common to the three amino acids. This, no doubt, accounts for the remarkable correlation among the plasma levels of the three amino acids in a variety of situations, such as in Type 1 and Type 2 diabetes.(Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes..2004)(Leucine and Protein Metabolism in Obese Zucker Rats..2013).These data suggest that the plasma concentrations of the individual BCAAs are not tightly defended and therefore not particularly important. Nor the catabolic fate of the different BCAAs appear to be an important consideration. (The medical biochemistry page).
However it was reported that feeding rats a leucine rich diet decreases plasma concentrations of isoleucine and valine and activates the hepatic BCKDH complex. This indicates that administration of leucine alone induces BCAA imbalance presumably because of inhibition of BCKDH kinase by KIC ( α-ketoisocaproate).(The peroxisome proliferator-activated receptor α Leu162Val polymorphism influences the metabolic response to a dietary intervention altering fatty acid proportions in healthy men..2005).
Leucine is ketogenic, valine is glucogenic, and isoleucine is both glucogenic and ketogenic. However, the fact that the catabolism of all three BCAAs is regulated at a common step suggests that it is not primarily driven by a need for glucose or a need for ketone bodies
In times of dietary surplus, the potentially toxic nitrogen of amino acids is eliminated via transaminations, deamination, and urea formation; the carbon skeletons are generally conserved as carbohydrate, via gluconeogenesis, or as fatty acid via fatty acid synthesis pathways. In this respect amino acids fall into three categories: glucogenic, ketogenic, or glucogenic and ketogenic. Glucogenic amino acids are those that give rise to a net production of pyruvate or TCA cycle intermediates, such as α-ketoglutarate or oxaloacetate, all of which are precursors to glucose via gluconeogenesis. All amino acids except lysine and leucine are at least partly glucogenic. Lysine and leucine are the only amino acids that are solely ketogenic, giving rise only to acetylCoA or acetoacetylCoA, neither of which can bring about net glucose production.
A small group of amino acids comprised of isoleucine, phenylalanine, threonine, tryptophan, and tyrosine give rise to both glucose and fatty acid precursors and are thus characterized as being glucogenic and ketogenic. Finally, it should be recognized that amino acids have a third possible fate. During times of starvation the reduced carbon skeleton is used for energy production, with the result that it is oxidized to CO2 and H2O.
Muscle is not a gluconeogenic tissue. Therefore, if valine and isoleucine are to be converger to glucose they cannot be completely oxidized in this tissue.
The catabolism of all three compounds initiates in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a BCAA aminotransferase (termed a branched-chain aminotransferase, BCAT), with α-ketoglutarate as amine acceptor. The mitochondrial BCAT isoenzyme is primarily responsible for initiating BCAA catabolism.
There are two genes encoding BCAT identified as BCAT1 and BCAT2. BCAT1 (located on chromosome 12p12.1) encodes a cytosolic version of the enzyme and the protein is identified as BCATc. BCAT2 (located on chromosome 19q13.33) encodes a mitochondrial version of the enzyme and this protein is designated BCATm. Expression of BCAT1 is seen in the CNS as well as several peripheral tissues. BCAT2 expression is observed in most non-neuronal tissues except the liver.
As a result, three different α-keto acids are produced and are oxidized using a common branched-chain α-keto acid dehydrogenase (BCKD), yielding the three different CoA derivatives. Subsequently the metabolic pathways diverge, producing many intermediates.
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 a-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.
Administration of ligands for peroxisome proliferator-activated receptor-α (PPARα) in rats causes activation of the hepatic BCKDH complex in association with a decrease in the kinase activity, which suggests that promotion of fatty acid oxidation upregulates the BCAA catabolism. Long-chain fatty acids are ligands for PPARα, and the fatty acid oxidation is promoted by several physiological conditions including exercise. These findings suggest that fatty acids may be one of the regulators of BCAA catabolism and that the BCAA requirement is increased by exercise.
The active dephosphorylated BCKD is also susceptible to allosteric inhibition, in particular by NADH and by the CoA esters that arise during BCAA catabolism.
The principal product from valine is propionylCoA, the glucogenic precursor of succinyl-CoA. Isoleucine catabolism terminates with production of acetylCoA and propionylCoA; thus isoleucine is both glucogenic and ketogenic. Leucine gives rise to acetylCoA and acetoacetylCoA, and is thus classified as strictly ketogenic.
There are a number of genetic diseases associated with faulty catabolism of the BCAAs. The most common defect is in the branched-chain α-keto acid dehydrogenase, BCKD. Since there is only one dehydrogenase enzyme for all three amino acids, all three α-keto acids accumulate and are excreted in the urine. The disease is known as Maple syrup urine disease because of the characteristic odor of the urine in afflicted individuals.
The occurrence of the diseases hypervalinemia and hyperleucinemia-hyperisoleucinemia are, apparently, due to the impaired transamination of valine alone, or of both leucine and isoleucine.(Hypervalinemia. A defect in valine transamination..1967). Such disorders challenge the conventional view that each of the BCAAs is transaminated by a common aminotransferase. It seems likely that these diseases are due to mutations in the common aminotransferase and that they affect its ability to act on each of the BCAAs. Nevertheless, this has not been established.
Leucine is utilized in the liver, adipose tissue, and muscle tissue. In adipose and muscle tissue, leucine is used in the formation of sterols, and the combined usage of leucine in these two tissues is seven times greater than its use in the liver(Metabolic fate of leucine: A significant sterol precursor in adipose tissue and muscle..2008).
Leucine is the only dietary amino acid that has the capacity to stimulate muscle protein synthesis(Manufacture and use of dairy protein fractions..2004). As a dietary supplement, leucine has been found to slow the degradation of muscle tissue by increasing the synthesis of muscle proteins in aged rats. While once seen as an important part of the three branch chained amino acids in sports supplements, leucine has since earned more attention on its own as a catalyst for muscle growth and muscular insurance(A leucine-supplemented diet restores the defective postprandial inhibition of proteasome-dependent proteolysis in aged rat skeletal muscle..2005). Supplement companies once marketed the "ideal" 2:1:1 ratio of leucine, iso-leucine and valine; but with furthered evidence that leucine is the most important amino acid for muscle building, it has become much more popular as the primary ingredient in dietary supplements.
Leucine potently activates the mammalian target of rapamycin kinase that regulates cell growth. Infusion of leucine into the rat brain has been shown to decrease food intake and body weight.( Hypothalamic mTOR signaling regulates food intake.. 2006).
Leucine toxicity, as seen in decompensated Maple Syrup Urine Disease (MSUD), causes delirium and neurologic compromise, and can be life-threatening. Leucine synthesis then becomes a useful selectable marker.
Leucine and muscle protein synthesis
Dietary amino acids stimulate muscle protein synthesis after food intake (Effect of dietary protein on translation initiation in rat skeletal muscle and liver, 1998). This anabolic effect may be attributed in part to an increase in amino acid supply to the muscle, thereby augmenting substrate availability for peptide synthesis. Additionally, individual amino acids may function as nutritional signaling molecules that regulate mRNA translation.
Leucine is unique among the branched-chain amino acids (BCAA) in its ability to stimulate protein synthesis in skeletal muscle and to enhance rates of translation initiation. In fact, neither valine nor isoleucine administration affected rates of protein synthesis.
A principal site in the regulation of translation initiation involves the binding of mRNA to the 40 S ribosome.
Oral administration of leucine facilitates this process by increasing the availability of eukaryotic initiation factor (eIF) 4E, a protein that binds the m7GTP cap present at the 5’-end of the mRNA, for binding eIF4G, a large, 220-kDa polypeptide that functions as a scaffold for eIF4E, the mRNA (via association with eIF4E) and the ribosome (via association with eIF3). The increase in eIF4E availability is due in part to the leucine-dependent hyperphosphorylation of the translational repressor, eIF4E-binding protein 1 (4E-BP1). Increased phosphorylation of 4E-BP1 decreases its affinity for eIF4E, thereby facilitating the association of eIF4E with eIF4G. Leucine was most effective among the BCAA in its ability to increase the amount of eIF4E available for active eIF4G • eIF4E complex formation and its administration reduces the amount of eIF4E in the phosphorylated form.
Moreover, oral administration of leucine enhances the phosphorylation state of S6K1, a ribosomal protein implicated in stimulating protein synthesis under conditions that promote 4E-BP1 phosphorylation (Orally administered leucine stimulates protein synthesis in skeletal muscle of postabsorptive rats in association with increased eIF4F formation, 2000).
The ability of leucine to promote the hyperphosphorylation of both 4E-BP1 and S6K1 suggests a common signaling pathway through which the amino acid upregulates translational efficiency (Oral administration of leucine stimulates ribosomal protein mRNA translation but not global rates of protein synthesis in the liver of rats, 2001).
Although leucine may independently signal to the translational apparatus to enhance rates of protein synthesis in muscle, the stimulation is transient. Sustained increases may require the full complement of amino acids to ensure adequate substrate for protein synthesis. Furthermore, elevations in serum insulin may be necessary to maintain enhanced rates of protein synthesis after oral administration of leucine.
Amino acids can enhance pancreatic insulin release. However, the stimulatory effects of oral leucine administration on both protein synthesis and translation initiation occurred without a concomitant increase in serum insulin concentration, but it’s possible that transient elevations in serum insulin occurred at an earlier time point and facilitated the protein synthetic response to leucine (Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway, 2000).
In fact, infusion of somatostatin, an inhibitor of pancreatic hormone release, inhibited the increase in serum insulin concentrations observed in response to leucine administration. Moreover, somatostatin blocked the stimulatory effect of leucine on muscle protein synthesis, attenuating the leucine-induced hyperphosphorylation of 4E-BP1 and partially inhibiting the leucine-induced phosphorylation of S6K1.
Although physiological increases in serum insulin do not independently stimulate protein synthesis in skeletal muscle (The response of muscle protein synthesis to nutrient intake in postabsorptive rats: the role of insulin and amino acids, 1986), a transient increase in the circulating concentration of the hormone may be permissive for the leucine-induced stimulation of protein synthesis (Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine, 2002).
The protein kinase referred to as mammalian target of rapamycin (mTOR), which lies downstream of protein kinase B (also referred to as Akt) in the phosphoinositol 3-kinase signaling pathway, might be a convergence point for both amino acid- and insulin-mediated effects on translation initiation (Leucine regulates translation of specific mRNAs in L6 myoblasts through mTOR-mediated changes in availability of eIF4E and phosphorylation of ribosomal protein S6, 1999; Bidirectional modulation of insulin action by amino acids, 1998). In fact, somministration of rapamycin, a specific inhibitor of mTOR, reduces rates of protein synthesis independently of leucine administration. These results suggest that the leucine-dependent stimulation of muscle protein synthesis is rapamycin sensitive in part and involves mTOR.
Nevertheless, results from several studies suggest that the leucine-dependent increase in skeletal muscle protein synthesis involves additional intracellular signaling pathways.
Activation of skeletal muscle mTOR results in increased protein synthesis and, thus, increased energy expenditure. Hypothalamic mTOR activation is also involved in the regulation of feeding behaviors. Of note is the fact that direct injection of leucine into the hypothalamus results in increased mTOR signaling leading to decreased feeding behavior and body weight. This effect is unique to leucine, as direct injection of valine, another BCAA, does not result in hypothalamic mTOR activation nor reductions in food intake or body weight.
The duration of the meal response is limited by energy status of the cell and inhibition of translation elongation factor 2 (eEF2). Leucine or carbohydrate supplements provided about 2 hours after consumption of a complete meal can extend the postprandial anabolic period of muscle protein synthesis, in a dose and time-dependent way. This response is associated with maintaining eEF2 activity and cellular energy. Leucine can provide energy to skeletal muscle through direct oxidation of the keto acid substrate (α-ketoisocaproate), but when compared with the carbohydrate supplements, the magnitude of the energy response to leucine appears to be disproportionately higher than the energy content in the leucine supplement (Post-meal responses of elongation factor 2 (eEF2) and adenosine monophosphate-activated protein kinase (AMPK) to leucine and carbohydrate supplements for regulating protein synthesis duration and energy homeostasis in rat skeletal muscle, 2012).
CONCLUSIONS: Leucine and exercise
BCAA supplementation before and after exercise has beneficial effects for decreasing exercise-induced muscle damage and promoting muscle-protein synthesis; this suggests the possibility that BCAAs are a useful supplement in relation to exercise and sports.
It is believed that BCAAs contribute to energy metabolism during exercise as energy sources and substrates to expand the pool of citric acid–cycle intermediates (anaplerosis) and for gluconeogenesis.
Leucine is special among the BCAAs, because it promotes muscle-protein synthesis in vivo when orally administered to animals. The leucine content of a protein source has an impact on protein synthesis, and affects muscle hypertrophy (The leucine content of a complete meal directs peak activation but not duration of skeletal muscle protein synthesis and mammalian target of rapamycin signaling in rats, 2009).
Leucine has been the most thoroughly investigated because its oxidation rate is higher than that of isoleucine or valine. Leucine is also closely associated with the release of gluconeogenic precursors, such as alanine, from muscle. Significant decreases in plasma or serum levels of leucine occur following aerobic (11 to 33%), anaerobic lactic (5 to 8%) and strength exercise (30%) sessions. The leucine content of protein is assumed to vary between 5 and 10%. There are suggestions that the current recommended dietary intake of leucine be increased from 14 mg/kg bodyweight/day to a minimum of 45 mg/kg bodyweight/day for sedentary individuals, and more for those participating in intensive training in order to optimise rates of whole body protein synthesis (Leucine supplementation and intensive training, 1999).
Leucine also seems to have both insulin-dependent and insulin-independent mechanisms for promoting protein synthesis (Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase, 2005).
Approximately 3 to 4 g of leucine per serving is needed to promote maximal protein synthesis (Amino acid ingestion improves muscle protein synthesis in the young and elderly, 2004).
Performing resistance exercise or ingesting amino acids alone stimulates muscle protein synthesis; however, the combined effects of ingesting essential amino acids following exercise appear to be more anabolic than either amino acids or exercise independently. Several studies have shown that amino acid ingestion in combination with exercise stimulates components of the mTOR signaling pathway (Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle, 2008).
In general, protein supplementation pre- and/or post-workout increases physical performance, training session recovery, lean body mass, muscle hypertrophy, and strength. Specific gains, however, differ based on protein type and amounts (The effect of resistance training combined with timed ingestion of protein on muscle fiber size and muscle strength, 2005). What is interesting about the studies of consumption of milk, for example, is that, despite leucine intake was suboptimal, yet they all showed improvements in LBM and strength. This raises the question of whether other components in milk could have contributed to the changes observed (Protein timing and its effects on muscular hypertrophy and strength in individuals engaged in weight-training, 2012).
The ingestion of essential amino acids prior to resistance exercise is more beneficial than post-ingestion in promoting protein synthesis, but these results did not hold true with respect to whey protein ingestion.
There is a limited time window within which to induce protein synthesis before a refractory period begins.
A combination of a fast-acting carbohydrate source such as maltodextrin or glucose should be consumed with the protein source, as leucine cannot modulate protein synthesis as effectively without the presence of insulin (hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase, 2005).
The consumption of essential amino acids and dextrose appears to be most effective at evoking protein synthesis prior to rather than following resistance exercise (Timing of amino acid-carbohydrate ingestion alters anabolic response of muscle to resistance exercise, 2001).
Consumption of BCAA before or during endurance exercise may prevent or decrease the net rate of protein degradation, may improve both mental and physical performance and may have a sparing effect on muscle glycogen degradation and depletion of muscle glycogen stores.
Dietary supplementation of the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) 3 g/day to humans undertaking intensive resistance training exercise resulted in an increased deposition of fat-free mass, an increase in strength and a decrease in muscle proteolysis. BCAA supplementation in combination with moderate energy restriction has been shown to induce significant and preferential losses of visceral adipose tissue and to allow maintenance of a high level of performance.
There is a tolerance level of BCAA ingestion in rats submitted to prolonged physical exercise. The studies on BCAA supplementation that have been conducted on physically active humans show that a rather large dietary excess of the three BCAAs is well tolerated when consumed in diets containing surfeit amounts of protein.
Fatigue during exercise involves both peripheral both central mechanisms.
During prolonged exercise to exhaustion, there is an increased flow through the glycolytic pathway, resulting in decreased glucose levels and the concomitant increase in plasma lactate concentration, which are important factors in the etiology of fatigue during exercise. The effects of chronic supplementation with BCAA on performance in trained rats do not involve changes in glucose metabolism.
Ammonia is a ubiquitous metabolic product, which concentration in several body compartments is elevated during exercise. Depending on the intensity and duration of exercise, muscle ammonia may be elevated to the extent that it diffuses from muscle to blood, can be carried to other organs and can also cross the blood-brain barrier. It seems reasonable to assume that exhaustive exercise may induce a state of acute ammonia toxicity which may be severe enough in critical regions of the central nervous system (CNS) to affect continuing coordinated activity. There have been numerous suggestions that elevated ammonia is associated with, or perhaps is responsible for, exercise fatigue.
In some studies, the greater chronic ingestion of BCAA, through the diet, increased the plasma concentration of ammonia.
Diets featuring high doses of chronically-administered BCAA may be toxic and lead to early fatigue during prolonged exercise.
Central fatigue is related to the increased release of neurotransmitters, particularly 5-hydroxytryptamine (serotonin). Exhaustive exercise results in a gradual increase in the concentration of plasma free fatty acids, which compete with tryptophan for binding to plasma protein albumin. Thus, there is an increased concentration of free tryptophan. BCAAs compete with free tryptophan by binding to the same transport of neutral amino acids in the blood-brain barrier. The entry of tryptophan into the central nervous system (CNS) is regulated by the ratio plasma free tryptophan. The decrease in glycogen stores, increased oxidation of BCAA and high concentration of plasma fatty acids act as important factors in increasing the synthesis of the neurotransmitter serotonin in the CNS, and this is dependent on the availability of tryptophan, a precursor of serotonin, in the CNS. The increased synthesis of serotonin during exercise may be related to the development of central fatigue, because this neurotransmitter has several physiological functions. Chronic BCAA supplementation was not effective in improving the main parameters indicative of central fatigue.
In conclusion, BCAAs emerge to be related to peripheral fatigue but not to central fatigue mechanisms (Effects of diets supplemented with branched-chain amino acids on the performance and fatigue mechanisms of rats submitted to prolonged physical exercise, 2012).
Diet and exercise training are also known to increase fat utilization during exercise. It is not known whether this can be enhanced further by dietary supplement interventions which increase fat oxidation in untrained individuals. Diets containing antioxidants and BCAAs are reported to have potential effects on fat utilization. Leucine was found to enhance fat oxidation in obese animals and overweight or obese subjects. It induced a significant increase in fat oxidation in muscle cells via an improvement in mitochondrial oxidative function. Leucine also affects adipose tissue, reducing fatty acid synthase expression in human adipocytes. Supplementation with leucine increases hepatic and muscle glycogen concentrations immediately after exercise, suggesting greater fat use during exercise.
The effects of leucine supplementation are not as pronounced as the effects observed when consuming a high-protein diet. This suggests that additional factors are likely involved in the effects of high-protein diets. One of these factors may be that consuming a high protein diet is associated with a reduction in total carbohydrate intake. The reduced carbohydrate intake would thus be associated with a reduction in hepatic lipogenesis and an increase in adipose tissue lipolysis. Although leucine alone is not as effective as high-protein diets at reducing body weight and food intake it cannot be discounted as an important dietary supplement.
Ilaria Alasia e Maria Sole Del Noce