Possible Interaction: Leucine and Sirolimus

“Within the periphery, BCAAs are essential AAs and are required for protein synthesis, and are key nitrogen donors in the form of Glu, Gln, and Ala. Leucine is an activator of the mammalian (or mechanistic) target of rapamycin , the master regulator of cell growth and proliferation.”

“ Leucine modulates the activity of energy and nutrient sensor pathways controlled by AMP-activated protein kinase and mammalian target of rapamycin in the hypothalamus.”

“First, leucine is known to stimulate the mammalian target of rapamycin pathway , which initiates translation and protein synthesis in muscle cells.”

“Although rapamycin (mTOR inhibitor) prevented this cardioprotective effect induced by Leu , wortmannin (PI3K inhibitor) did not interfere with this effect.”

“…,RAPA (especially at 1.2 mg/kg BW) decreased the crude protein, αs1-… contents (Asp, Thr, Ser, Glu, Gly, Ala, Cys, Val, Met, Ile, Leu , Tyr, Lys, His, Arg, and Pro) of crop milk (P < 0.05) …, and uric acid in the serum of breeding pigeons (P < 0.05).”

“Once administrated with LY294002 (PI3K inhibitor) and Rapamycin (mTOR inhibitor), leucine mediated by the anti-atrophic effects was nearly blunted.”

“Supplementation of leucine improved the phosphorylation of mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E-binding protein 1 (4EBP1) and substrates ribosomal protein S6 kinase 1 (p70S6K).”

“Under nitrogen fertilization, Leu and Met accumulated in the green morph enhanced the target of rapamycin (TOR) signaling pathway, which consequently increased fecundity by promoting vitellogenin synthesis.”

“However, when the cells were exposed to rapamycin (80nM), leucine inhibited the expression of SMAD and FoxO3a, showing that leucine was able to modulate the degradation pathway when protein synthesis is compromised.”

“In conclusion, the present study shows that leucine can modulate degradation pathways even under inhibition of mTOR by rapamycin.”

“Phosphorylation of the mTORC1 target proteins 4EBP‐1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and … this did not appear to be enhanced with increasing leucine doses, this effect was completely ablated by co‐incubation with the mTOR inhibitor rapamycin, … leucine ….”