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Dietary branched-chain amino acids (BCAA) are marketed to athletes as a supplement that stimulates protein formation in muscle and reduces muscle breakdown. Branched-chain amino acids are those amino acids that have a side chain consisting of an aliphatic group with a branch point, including leucine, isoleucine, and valine (Figure 1). They account for 35, percent of the essential amino acids found in muscle proteins.
Figure 1. Branched-chain amino acid properties
Amino AcidR-grouppKa amino grouppKA carboxyl group
ValineC, H(C, H, start subscript, 3, end subscript)start subscript, 2, end subscript9, point, 742, point, 30
IsoleucineC, H(C, H, start subscript, 3, end subscript)C, H, start subscript, 2, end subscriptC, H, start subscript, 3, end subscript9, point, 762, point, 32
LeucineC, H, start subscript, 2, end subscriptC, H(C, H, start subscript, 3, end subscript)start subscript, 2, end subscript9, point, 742, point, 32
The medication rapamycin has important immunosuppressive effects and its mechanism has been well studied. The mammalian target of rapamycin (mTOR), is a conserved serine/threonine protein kinase that regulates protein metabolism. mTOR integrates intracellular inputs such as growth factors (in particular BCAA amino acids) to promote protein translation. Activated mTOR results in the phosphorylation of a translation initiation protein called eIF-4EBP1. Unphosphorylated eIF-4EBP1 blocks translation by sequestering a different translation initiation protein called eIF4E, which is responsible for binding the mRNA cap and bringing the mRNA transcript to the ribosome. Phosphorylation of eIF-4EBP1 by mTOR causes eIF-4EBP1 to release eIF4E, and results in the initiation of translation.
Recently, studies in animal models have suggested that certain BCAAs are more effective than others in activating mTOR (Figure 2), suggesting that nutritional supplements could be more effectively targeted toward building muscle through this pathway.
Figure 2. Percentage phosphorylated eIF-4EBP1
What is the pI, or isoelectric point, of I) isoleucine, II) leucine, and III) valine?
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