Cytosolic pyruvate kinase catalyzes the transfer of a high-energy phosphate from phosphoenolpyruvate to ADP, forming pyruvate and ATP. This reaction, an instance of substrate-level phosphorylation, is essentially irreversible under physiological conditions.
Four isozymes of human pyruvate kinase have been described, L, R, M1 and M2. Isozymes L and R are encoded by alternatively spliced transcripts of the PKLR gene; isozymes M1 and M2 are encoded by alternatively spliced transcripts of PKM2. In the body, L pyruvate kinase is found in liver (Tani et al. 1988), R in red blood cells (Kanno et al. 1991), M1 in muscle, heart and brain (Takenaka et al. 1991), and M2 in early fetal tissues and tumors (e.g., Lee et al. 2008). In all cases, the active form of the enzyme is a homotetramer, activated by fructose 1,6-bisphosphate (Valentini et al. 2002; Dombrauckas et al. 2005). Mutations in PKLR have been associated with hemolytic anemias (e.g., Zanella et al. 2005).
|pyruvate kinase tetramer||pyruvate kinase activity (0004743)|
|15996096||Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis||Biochemistry||2005|
|1896471||cDNA cloning of human R-type pyruvate kinase and identification of a single amino acid substitution (Thr384----Met) affecting enzymatic stability in a pyruvate kinase variant (PK Tokyo) associated with hereditary hemolytic anemia||Proc Natl Acad Sci U S A||1991|
|18191611||Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 in regulating transcription||Int J Biochem Cell Biol||2008|
|2040271||Isolation and characterization of the human pyruvate kinase M gene||Eur J Biochem||1991|
|3126495||Human liver type pyruvate kinase: complete amino acid sequence and the expression in mammalian cells||Proc Natl Acad Sci U S A||1988|
|11960989||Structure and function of human erythrocyte pyruvate kinase. Molecular basis of nonspherocytic hemolytic anemia||J Biol Chem||2002|
|15982340||Red cell pyruvate kinase deficiency: molecular and clinical aspects||Br J Haematol||2005|