The Leucine Trigger for mTOR describes the specific, potent role of the essential branched-chain amino acid, Leucine, in directly activating the mechanistic Target of Rapamycin (mTOR) signaling pathway within muscle and other anabolic tissues. Leucine acts as a critical nutrient sensor, providing a signal of substrate availability that is indispensable for initiating the complex cellular machinery responsible for muscle protein synthesis (MPS). Clinically, leveraging this trigger is a key strategy for maximizing the anabolic response to protein feeding, especially following resistance exercise.
Origin
This concept emerged from molecular biology and nutritional science research that identified mTOR as the central regulator of cell growth and metabolism in response to nutrients, energy, and stress. Subsequent studies isolated Leucine as the single most potent amino acid activator of this pathway. The term ‘trigger’ emphasizes its role as the crucial initiating signal, distinct from the other amino acids which serve primarily as building blocks.
Mechanism
Leucine is transported into the cell and metabolized to its derivative, alpha-ketoisocaproate (α-KIC), which interacts with a protein complex known as Sestrin2. The binding of Leucine to Sestrin2 releases GATOR2, a complex that is an upstream regulator of mTORC1. This cascade culminates in the activation of mTORC1, which then phosphorylates downstream targets like S6K1 and 4E-BP1. The phosphorylation of these targets subsequently promotes the translation of mRNA into new protein, thereby accelerating the rate of muscle hypertrophy and repair.
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