Amino acids: Dietary supplements and the mTOR pathway

Dietary branched-chain amino acids (BCAAs) are marketed to athletes as supplements that stimulate protein formation in muscle and reduce muscle breakdown. BCAAs are amino acids that have a side chain consisting of an aliphatic group with a branch point; they include leucine, isoleucine, and valine (Figure 1). BCAAs account for 35% of the essential amino acids found in muscle proteins.

Table 1 Branched-chain amino acid (BCAA) properties

The mammalian target of rapamycin (mTOR) is a conserved serine/threonine protein kinase that regulates protein metabolism. mTOR integrates intracellular inputs, such as BCAAs and growth factors, to promote protein translation. The activation of mTOR results in the phosphorylation of a translation initiation protein called eIF4EBP1. Unphosphorylated eIF4EBP1 blocks translation by sequestering a different translation initiation protein called eIF4E. eIF4E is responsible for binding the mRNA cap and bringing the mRNA transcript to the ribosome. Phosphorylation of eIF4EBP1 by mTOR causes eIF4EBP1 to release eIF4E, resulting in the initiation of translation.

Recently, studies in animal models have suggested that certain BCAAs are more effective than others in activating mTOR (Figure 1); this suggests that nutritional supplements could be more effectively targeted toward building muscle through this pathway. Figure 1 shows the percentage of phosphorylated eIF4EBP1 in two mice at baseline (control) and following supplementation with each of the three BCAAs investigated here.

Figure 1 Percentage of phosphorylated eIF4EBP1 following supplementation; error bars represent standard error