PKM1: Proteins and Enzymes

Pyruvate kinases are glycolytic enzymes that transfer a phosphate group from phosphoenolpyruvate to ADP generating pyruvate and ATP. There are 4 isozymes of pyruvate kinase in mammals: L, R, M1 and M2. L type is major isozyme in the liver, R is found in red cells, M1 is the main form in muscle, heart and brain, and M2 is found in early fetal tissues as well as in most cancer cells. The M1 isoform differs from the M2 isoform due to a change in sequence between residues 389-433. In the presence of D-fructose 1,6-bisphosphate (FBP) the monomer reversibly forms the highly active tetrameric form. This tetramer is associated with the glycolytic enzyme complex and activates the pyruvate kinase activity. A nearly inactive dimeric form is associates with tumor cells.