188.8.131.52 - Pyruvate kinase
- Phosphoenol transphosphorylase.
- Phosphoenolpyruvate kinase.
ATP + pyruvate = ADP + H(+) + phosphoenolpyruvate
There are no Cofactors for this Enzyme
Pyruvate kinase catalyses the final step of glycolysis and is allosterically regulated by fructose-1,6-bisphosphate. It requires two equivalents divalent cation, one of which binds to the enzyme as a complex with the nucleotide substrate, as well as activation by K+. As opposed to mammalian pyruvate kinase, the bacterial enzyme works in a K+ independent manner.
The enzyme is also known to catalyse a variety of side reactions, including the decarboxylation of oxalacetate, the enolisation of pyruvate, ATP-dependent phosphorylation of alpha-hydroxy or alpha-thio carboxylates, ATP- and bicarbonate-dependent phosphorylations of fluoride and of hydroxylamine and to also function as an ATP- and bicarbonate-dependent ATPase. These side activities reflect the capacity of the active site to labilise the gamma-phosphate of ATP or to stabilise the enolate of pyruvate [PMID:9308890].
There are four isozymes of pyruvate kinase in mammals (L, R, M1, M2) encoded by two different genes: PKLR and PKM. The L and R isozymes are generated from the PKLR by differential splicing of RNA; the M1 and M2 forms are produced from the PKM gene by differential splicing. 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. This entry represents the PKM gene products.
|AA||Uniprot||Uniprot Resid||PDB||PDB Resid|
overall product formed, overall reactant used, proton transfer, intermediate formation, bimolecular nucleophilic substitution, native state of enzyme regenerated, dephosphorylation, intermediate collapse
Phosphoryl transfer from PEP to M(II)ADP occurs by an apparent SN2 mechanism with an inversion of configuration at the phosphoryl group, to yield the enolate of pyruvate and M(II)ATP. The presence of either a Mn or Mg divalent cation is essential for catalytic activity [PMID:8193145]. The monovalent cation, K+, does not directly contact the substrate or intermediate, but instead is thought to influence the structure of the active site though interactions with the positively charged resides Arg72, Arg119 and Lys269 [PMID:8193145].
Thr237 and the Mn(II) cation increase the acidity of water through hydrogen bonding and charge stabilisation, respectively, generating a specific acid to act towards the enolate intermediate. A solvent molecule at the active site stereospecifically protonates the enolate at the 2-si face of the double bond to form keto pyruvate. Kinetic and pH studies have shown the proton to originate from a solvent molecule [PMID:15568816]. The divalent cation is thought to enhance the acidity of the solvent molecule, rather than the monovalent cation [PMID:12562754].
There are no kinetic parameters information for this Enzyme
- Mitapivat: A Review in Pyruvate Kinase Deficiency in Adults.
- Psychometric validation of the Pyruvate Kinase Deficiency Diary and Pyruvate Kinase Deficiency Impact Assessment in adults in the phase 3 ACTIVATE trial.
- Mitapivat: A Novel Treatment of Hemolytic Anemia in Adults with Pyruvate Kinase Deficiency.
- Metabolomic analysis of Drosophila melanogaster larvae lacking Pyruvate kinase.
- Pyruvate kinase M2 (PKM-2) expression and prognostic significance in glioblastoma patients.
- Application of recombinant human pyruvate kinase in recombinase polymerase amplification.
- Pyruvate Kinase Deficiency Causing Priapism.
- The 2.4 Å structure of Zymomonas mobilis pyruvate kinase: Implications for stability and regulation.
- Pyruvate kinase M in germ cells is essential for sperm motility and male fertility but not spermatogenesis.
- Pyruvate kinase is post-translationally regulated by sirtuin 2 in Aedes aegypti mosquitoes.
- Mitapivat: A Quinolone Sulfonamide to Manage Hemolytic Anemia in Adults With Pyruvate Kinase Deficiency.