Acetate Metabolism in Physiology, Cancer, and Beyond.

Acetate and the related metabolism of acetyl-coenzyme A (acetyl-CoA) confer numerous metabolic functions, including energy production, lipid synthesis, and protein acetylation. Despite its importance as a nutrient for cellular metabolism, its source has been unclear. Recent studies have provided evidence to support the existence of a de novo pathway for acetate production derived from pyruvate, the end product of glycolysis. This mechanism of pyruvate-derived acetate generation could have far-reaching implications for the regulation of central carbon metabolism. In this Opinion, we discuss our current understanding of acetate metabolism in the context of cell-autonomous metabolic regulation, cell–cell interactions, and systemic physiology. Applications relevant to health and disease, particularly cancer, are emphasized. Our understanding of the origin of acetate in physiological and disease states is currently evolving and is not limited to exogenous acetate uptake. The regulation of the production of endogenous pyruvate-derived acetate remains largely unknown. Pathways of metabolism during periods of nutritional excess and limitation allow metabolic coupling to confer fitness advantages to proximal and systemic cellular partners. Preferential uptake of acetate by certain tissues is driven not only by the availability of transporters but by environmental pressures such as hypoxia and nutrient scarcity. [ABSTRACT FROM AUTHOR]