Figure 2. Roles for metabolism in gene regulation.

Scheme to categorize the distinct outcomes of nutrient uptake, which generates energy and metabolites. Energy is expended by hydrolysis of ATP into ADP and inorganic phosphate (Pi), and this flux controls the rate at which biochemical processes such as transcription, translation, and molecular degradation occur. Certain signaling pathways such as AMPK actively sense ATP status and regulate specific genes in response. Generation of certain metabolites regulates gene expression because these metabolic substrates can act as rate-limiting factors in modulating epigenetic and protein modifications. Other metabolic processes can tune these modifications. Examples include chaperone-mediated autophagy (CMA), an alternate protein degradation mechanism from the proteasome, and efflux of lactate from cells, leading to higher intracellular pH.