What happens when there is a buildup of acetyl-CoA?

When there is a buildup of acetyl-CoA, the conversion of pyruvate to oxaloacetate occurs as a means to help regulate the metabolic pathways involved in energy metabolism. Acetyl-CoA serves as a key intermediate in several metabolic pathways, including the citric acid cycle (Krebs cycle).

When the levels of acetyl-CoA are high, it indicates that the energy needs of the cell are being met, and there may be a preference for using acetyl-CoA in various biosynthetic processes, including the synthesis of fatty acids or cholesterol. The conversion of pyruvate to oxaloacetate, facilitated by the enzyme pyruvate carboxylase, is an important anaplerotic reaction that helps replenish the intermediates of the citric acid cycle. This step requires biotin as a cofactor and contributes to maintaining pool sizes of critical metabolites within the cycle.

This reaction can also signal the entry of pyruvate into gluconeogenesis, especially when energy stores are high and glucose synthesis is favored. Therefore, the buildup of acetyl-CoA stimulates the synthesis of oxaloacetate from pyruvate, aligning metabolic pathways to meet the energy and biosynthetic needs of the cell.