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Synthesis for BCAAs occurs in all location of plants, within the plastids of the cell, as determined by presence of mRNAs which encode for enzymes in the metabolic pathway.

BCAAs provide several metabolic and physiologic roles. Metabolically BCAAs promote protein synthesis and turnover, signaling pathways, and metabolism of glucose. In addition 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. Lastly BCAAs share the same transport protein into the brain with aromatic amino acids (Trp, Tyr, and Phe). Once in the brain BCAAs may have a role in protein synthesis, synthesis of neurotransmitters, and production of energy.

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. Threonine dehydrogenase catalyzes the deamination and dehydration of threonine to 2-ketobutyrate and ammonia. Isoleucine forms a negative feedback loop with Threonine Dehydrogenase. Acetohydroxyacid synthase is the first enzyme for the parallel pathway performing condensation reaction in both steps – condensation of pyruvate to acetolacetate in the valine pathway and condensation of pyruvate and 2-ketobutyrate to form acetohydroxybtylrate in the isoleucine pathway. Next ketoacid reductisomerase reduces the accetohydroxy acids from the previous step to yield dihydroxyacids in both the valine and isoleucine pathways. Dihydroxyacid dehygrogenase converts the dihyroxyacids in the next step. The final step in the parallel pathway is conducted by amino transferase, which yields the final products of valine and isoleucine. A series of four more enzymes - isopropylmalate synthase, isopropylmalate isomerase, isopropylmalate dehydrogenase, and aminotransferase - are necessary for the formation of leucine from 2-oxolsovalerate.

Cell Signaling
While most amino acids are oxidized in the liver, BCAAs are primarily oxidized in the skeletal muscle and other peripheral tissues. The effects of BCAA administration on muscle growth in rat diaphragm was tested, and concluded that not only does a mixture of BCAAs alone have the same effect on growth as a complete mixture of amino acids, but an amino acid mixture with all but BCAAs has no effect on rat diaphragm muscle growth. 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 mixure 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. P70 S6 kinase is part of the mammalian target of rapamycin complex (mTOR) signaling pathway, and has been show to allow adaptive hypertrophy and recovery of rat muscle. 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 siz hour stimulatory effect and increased protein synthesis by phosphorylation of p70 S6 kinase in skeletal muscles. Following resistance exercise, without BCAA administration, a resistance exercise session does not affect mTOR phosphorylation and even produces a decrease in Akt phosphorylation. Some phosphorylation of p70 S6 kinase was discovered. When BCAAs were administered following a training session, sufficient phosphorylation of p70 S6 kinase and S6 indicated activation of the signaling cascade.

BCAA roles in Diabetes Mellitus
In addition to cell signaling, the mTOR pathway also plays a role inbeta cell growth leading to insulin secretion. High glucose in the blood begins the process of the mTOR signaling pathway, 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. In the cell the increased activity of mTOR complex causes eventual inability of beta cells to release insulin and an inhibitory effect on S6 kinase leading to insulin resistance in the cells.

Both humans and rats were tested for prevalence of BCAA signatures leading to insulin resistance. Human subjects’ bod mass index was compared to concentration of BCAAs in their diet, as well as insulin resistance level. It was determined that subjects considered obese had higher metabolic signatures of BCAAs and higher resistance to insulin than those lean individuals with a lower body mass index. In addition rats fed a diet high in BCAAs had increased rates of insulin resistance and impaired phosphorylation of enzymes within their muscles.

A couple pharmaceuticals have been discovered to treat insulin resistance associated with diabetes. Metformin is able to activate AMP kinase which phosphorylates proteins involved in the mTOR pathway, as well as lead to the progression of mTOR complex from its inactive state to its active state. It is suggested that Metformin acts as a competitive inhibitor to the amino acid leucine in the mTOR pathway. Resveratrol inhibits the mTOR complex through increased concentration of AMP kinase which renders it inactive after its activation byleucine. In addition Resveratrol was able to allow beta cells to function normall in secreting insulin, even under the stress of increased concentration of branched chain amino acids. A cure for diabetes is still not available, but options such as Metformin and Resveratrol show treatment for insulin resistance associated with diabetes.