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AICAR and metformin, both activators of AMPK signaling, reproduce key aspects of exercise-induced metabolic adaptation and have been shown to improve recognition memory and neuroplasticity [73, 74]

To overcome this limitation to learn about the general principles of enzyme activation across pathways, we have herein reconstructed a network of enzymemetabolite activatory interactions by enriching the genome-scale metabolic network of Saccharomyces cerevisiae (Data ref: Zhang et al, 2023) with cross-species enzyme activation data from the Braunschweig Enzyme Database (BRENDA) database, which has collected enzyme kinetic data over a century of biochemical research (Data ref: Chang et al, 2021)

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