A branched-chain amino acid is an amino acid having an aliphatic side-chain with a branch . Among the proteinogenic amino acids, there are three BCAAs: leucine, isoleucine, and valine. Non-proteinogenic BCAAs include 2-aminoisobutyric acid.
The three proteinogenic BCAAs are among the nine essential amino acids for humans, accounting for 35% of the essential amino acids in muscle proteins and 40% of the preformed amino acids required by mammals. Synthesis for BCAAs occurs in all locations of plants, within the plastids of the cell, as determined by presence of mRNAs which encode for enzymes in the metabolic pathway.
BCAAs fill several metabolic and physiologic roles. Metabolically, BCAAs promote protein synthesis and turnover, signaling pathways, and metabolism of glucose. Oxidation of BCAAs may increase fatty acid oxidation and play a role in obesity. Physiologically, BCAAs take on roles in the immune system and in brain function. BCAAs are broken down effectively by dehydrogenase and decarboxylase enzymes expressed by immune cells, and are required for lymphocyte growth and proliferation and cytotoxic T lymphocyte activity. For a 70 kg person this equates to 2.9, 1.3 and 1.7 g/day. Diets that meet or exceed the RDA for total protein, meet or exceed the RDAs for branched-chain amino acids.
Research
Dietary BCAAs have been used in an attempt to treat some cases of hepatic encephalopathy. They can have the effect of alleviating symptoms of hepatic encephalophathy, but there is no evidence they benefit mortality rates, nutrition, or overall quality of life as further research is necessary.
Certain studies suggested a possible link between a high incidence of amyotrophic lateral sclerosis among professional American football players and Italian soccer players, and certain sports supplements including BCAAs.
Yet any link between BCAAs and ALS remains to be fully established. While BCAAs can induce a hyperexcitability similar to the one observed in mice with ALS, current work does not show if a BCAA-enriched diet, given over a prolonged period, actually induces ALS-like symptoms. BCAA-restricted diets improve glucose tolerance and promote leanness in normal weight mice, restores insulin sensitivity and normal body weight to obese mice and promotes insulin sensitivity in obese rats.
Synthesis
Five enzymes play a major role in the parallel synthesis pathways for isoleucine, valine, and leucine: threonine dehydrogenase, acetohydroxyacid synthase, ketoacid reductoisomerase, dihydroxyacid dehygrogenase and aminotransferase.
Enzymes involved are branched chain aminotransferase and 3-methyl-2-oxobutanoate dehydrogenase.
Cell signaling
While most amino acids are oxidized in the liver, BCAAs are primarily oxidized in the skeletal muscle and other peripheral tissues. Administration of either isoleucine or valine alone had no effect on muscle growth, although administration of leucine alone appears to be nearly as effective as the complete mixture of BCAAs. Leucine indirectly activates p70 S6 kinase as well as stimulates assembly of the eIF4F complex, which are essential for mRNA binding in translational initiation. At rest protein infusion stimulates protein synthesis 30 minutes after start of infusion, and protein synthesis stays elevated for another 90 minutes. Infusion of leucine at rest produces a six-hour stimulatory effect and increased protein synthesis by phosphorylation of p70 S6 kinase in skeletal muscles. High glucose in the blood begins the process of the mTOR signaling pathway, in which leucine plays an indirect role. The combination of glucose, leucine, and other activators cause mTOR to start signaling for the proliferation of beta cells and the secretion of insulin. Higher concentrations of leucine cause hyperactivity in the mTOR pathway, and S6 kinase is activated leading to inhibition of insulin receptor substrate through serine phosphorylation. High levels of lactic acid cause glucose metabolism to stop in order to reduce further reduction of pH. BCAA supplementation has been shown to decrease levels of lactic acid in the muscle, allowing glucose metabolism to continue. This results in reduced rates of glycogenolysis in the liver and consequently lower plasma levels of glucose. However, studies done regarding long term effects of BCAAs on glucose levels have shown that consistent supplementation of BCAAs do not have a notable effect on blood glucose levels outside of exercise.
BCAAs are also found to reduce the increase in serum levels of ammonia that occurs during exercise. This is done by increasing the amount of ammonia used in glutamine synthesis, preventing an over-accumulation of ammonia in the blood.
In addition, BCAA supplementation has been shown to decrease levels of creatine kinase in muscle cells post exercise. Creatine kinase is an indicator of muscle damage, and is responsible for transferring a phosphate group from ATP to create a phosphocreatine molecule. BCAA supplementation has been shown to decrease levels of creatine kinase, leading to higher levels of intracellular ATP and a lessened sense of fatigue.
