Pyruvate Kinase M2 (PKM2)

Pyruvate kinase M2 (PKM2) is a critical enzyme in cellular metabolism, specifically catalyzing the final step of glycolysis: the conversion of phosphoenolpyruvate (PEP) to pyruvate, generating ATP in the process. PKM2 is one of four pyruvate kinase isoforms found in vertebrates and is encoded by alternative splicing of the PKM gene. It plays essential roles not only in energy production but also in regulating cell growth, gene expression, and metabolic reprogramming—especially under conditions such as cancer and inflammation. PKM2 can exist as either an active tetramer or a less active dimer. Tetrameric form promotes glycolytic flux while the dimeric form favors accumulation of upstream metabolites for biosynthetic processes—this state predominates in proliferating cells like cancer cells. Beyond its metabolic role, PKM2 acts as a protein kinase and transcriptional coactivator influencing expression of genes linked to proliferation, angiogenesis, immune evasion, and inflammation responses. Elevated levels are observed across various cancers, making it an attractive target for anti-cancer therapies. Modulators that stabilize its tetrameric state are being explored to reverse tumor-specific metabolic changes.

Modulation of PKM2 tetramer/dimer equilibrium