The study investigates the role of amino acids in regulating the mammalian target of rapamycin (mTOR) kinase, which is crucial for protein translation, cell growth, and autophagy. The research identifies L-glutamine as a rate-limiting factor that sensitizes essential amino acids (EAA) and growth factors to activate mTOR. L-glutamine uptake is regulated by SLC1A5, and its loss inhibits cell growth and activates autophagy. The molecular basis for L-glutamine sensitivity involves SLC7A5/SLC3A2, a bidirectional transporter that exchanges L-glutamine for EAA. Certain tumor cell lines with high L-glutamine levels bypass the need for L-glutamine uptake and are primed for mTOR activation. The study concludes that L-glutamine flux regulates mTOR, translation, and autophagy to coordinate cell growth and proliferation.The study investigates the role of amino acids in regulating the mammalian target of rapamycin (mTOR) kinase, which is crucial for protein translation, cell growth, and autophagy. The research identifies L-glutamine as a rate-limiting factor that sensitizes essential amino acids (EAA) and growth factors to activate mTOR. L-glutamine uptake is regulated by SLC1A5, and its loss inhibits cell growth and activates autophagy. The molecular basis for L-glutamine sensitivity involves SLC7A5/SLC3A2, a bidirectional transporter that exchanges L-glutamine for EAA. Certain tumor cell lines with high L-glutamine levels bypass the need for L-glutamine uptake and are primed for mTOR activation. The study concludes that L-glutamine flux regulates mTOR, translation, and autophagy to coordinate cell growth and proliferation.