Researchers from the University of Seville and Ben-Gurion University of the Negev have identified the molecular details governing the regulation of pyruvate kinase, an enzyme critical for sugar metabolism and linked to cell proliferation and growth. These findings were published in the scientific journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).\n\nThe study demonstrates that acetylation, a reversible chemical modification, impacts the dynamics and function of pyruvate kinase. In healthy cells, this mechanism fine-tunes metabolism based on environmental conditions. However, in conditions like cancer, a loss of this control can reroute metabolic flow and promote uncontrolled cell proliferation.\n\nPyruvate kinase exists in two variants: PKM1, found in adult tissues, and PKM2, present in both adult and embryonic tissues. The researchers utilized biochemical, biophysical, structural, and computational simulation techniques to show that acetylation at specific positions inhibits the enzyme's function and reduces its stability. They also discovered that certain acetylations affect each variant differently, indicating variant-specific regulatory mechanisms.\n\nUnderstanding these molecular regulatory mechanisms of pyruvate kinase offers insights into the metabolic alterations that drive the proliferation of cancer cells and provides crucial information for interpreting its functional behavior in disease contexts like cancer.