PKM1PKM2

PKM1 and PKM2 are isoforms of pyruvate kinase M produced by alternative splicing of the PKM gene. They differ by the inclusion of mutually exclusive exons and have distinct kinetic properties and cellular roles.

The PKM gene yields PKM1 when exon 9 is included and PKM2 when exon 10 is included. Splicing factors such as PTBP1 influence this decision, promoting PKM2 expression in proliferating cells.

PKM1 forms a constitutively active tetramer with high pyruvate kinase activity, supporting efficient glycolysis for energy production. PKM2 can assemble into either a low-activity dimer or a high-activity tetramer, enabling metabolic flexibility that can favor biosynthesis when needed by the cell.

PKM2 activity is regulated allosterically by fructose-1,6-bisphosphate and by various post-translational modifications and protein interactions, allowing shifts between energy production and the generation of biosynthetic precursors.

In adult tissues, PKM1 is prevalent in cells with oxidative metabolism, such as brain and muscle, while PKM2 is common in embryonic and proliferating tissues, including many cancers.

The PKM1/PKM2 switch is linked to metabolic reprogramming in cancer and to broader growth-control processes. Targeting PKM2 splicing or activity has been explored as an anti-cancer strategy, reflecting interest in redirecting cancer metabolism.

Research continues on non-metabolic roles of PKM2, including nuclear functions in transcriptional regulation, and on pharmacological agents that modulate PKM2 to influence tumor metabolism.