Pyruvate kinase PKM (PKM2) (PKM2)

Pyruvate kinase PKM (specifically the M2 isoenzyme, PKM2) is a critical glycolytic enzyme that catalyzes the final rate-limiting step of glycolysis, converting phosphoenolpyruvate (PEP) and ADP into pyruvate and ATP (UniProt P14618). PKM2 is uniquely characterized by its ability to switch between a highly active tetrameric form and a less active dimeric form, a transition regulated by allosteric effectors like fructose-1,6-bisphosphate and post-translational modifications (PubMed: 15996096, 1854723). In cancer cells, the dimeric form predominates, facilitating the Warburg effect by allowing glycolytic intermediates to be diverted into biosynthetic pathways for rapid cell proliferation (PubMed: 18337815, 20847263). Beyond its metabolic function, PKM2 translocates to the nucleus where it acts as a protein kinase and transcriptional co-activator, promoting the expression of genes involved in the cell cycle and apoptosis resistance (PubMed: 22056988, 22306293). Due to its overexpression in various tumors and its role in metabolic reprogramming, PKM2 is a major therapeutic target; pharmacological strategies include small-molecule activators that stabilize the tetramer to suppress tumor growth and inhibitors that block its non-metabolic functions (PubMed: 22901803, 24120661). Additionally, PKM2 is increasingly recognized for its roles in inflammation and neurodegenerative diseases, expanding its potential as a clinical target (PubMed: 31243156, 31866844).

Other names

Pyruvate kinase muscle isozymePKMPK2PK3TCBOIP3CTHBPTHBP1Pyruvate kinase 2/3Tumor M2-PKCytosolic thyroid hormone-binding protein

Allosteric activation to stabilize the tetrameric form (promoting oxidative phosphorylation) or inhibition to stabilize the dimeric form (reducing glycolytic flux and non-metabolic signaling).