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Amino acid homeostasis is the complex physiological process by which cells and organisms maintain optimal concentrations of amino acids to support protein synthesis, energy production, and signaling. It is regulated by a network of sensors, primarily the mechanistic target of rapamycin complex 1 (mTORC1), which promotes anabolic processes when nutrients are abundant, and the general control nonderepressible 2 (GCN2) kinase, which triggers an adaptive stress response during scarcity (Efeyan et al., 2015; Bröer & Bröer, 2017). Additionally, various solute carrier (SLC) transporters facilitate the movement of amino acids across membranes to balance supply and demand. Dysregulation of this system is a hallmark of cancer, where cells often overexpress transporters to fuel rapid proliferation, and metabolic disorders such as obesity and type 2 diabetes. Because it is a systemic process rather than a single molecule, therapeutic strategies typically target specific nodes within the pathway, such as mTOR inhibitors or specific transporter antagonists, to achieve clinical effects.
Drugs do not target amino acid homeostasis as a single entity; instead, they modulate specific components such as inhibiting the mTORC1 pathway, blocking amino acid transporters like LAT1 (SLC7A5), or activating metabolic sensors like AMPK to restore or disrupt nutrient balance (Bröer & Bröer, 2017; Efeyan et al., 2015).
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