A demand-based framework explains prioritization strategies upon transient limitations of different amino acids

Cells require disparate amounts of distinct amino acids, which themselves have discrete biosynthetic costs. However, it remains unclear if and how cells respond differently to their scarcity. To explore this, we re-organized amino acids into distinct groups based on their metabolic origins. Subsequently, using yeast we assessed responses to transient disruptions in amino acid supply, and uncover diverse restoration responses for distinct amino acids. Cells hierarchically prioritize restoring glutamate-, sulfur-, pentose-phosphate- and pyruvate-derived amino acids. Particularly, the strongest response is to the glutamate-derived amino acid arginine. We find that the extent and priority of the restoration response is determined by the composite demand for an amino acid, coupled with low individual biosynthetic costs of that amino acid. We propose that cells employ a conserved strategy guided by the law of demand, to prioritize amino acids restoration upon transient limitation.