Question

What activates pyruvate kinase, what is this activation called, and why does it occur?

Answer 1

Pyruvate Kinase is an enzyme that is helps in the process of glycolysis. The function of the pyruvate kinase is to catalyze the last step of the glycolysis process; thereby, generating the second ATP of glycolysis and pyruvate. It catalyzes the reaction by transferring the phosphate group from phosphoenolpyruvate (PEP) to ADP.

Pyruvate Kinase couples the free energy of PEP cleavage to the generation of ATP during the synthesis of the, pyruvate. This reaction requires one K+ and two Mg2+ cations which is to be used in two steps.

It starts with the nucleophilic attack of the PEP phosphorous atom by β-phosphoryl oxygen of ADP, this step displaces enolpyruvate while forming ATP.

In the next step, enolpyruvate tautomerizes to pyruvate. The formation of a high-energy intermediate by enolase in the 9th reaction of glycolysis allows for the synthesis of ATP in this reaction. Though the hydrolysis of 2PG is insufficient in driving the synthesis of ATP, the dehydration of 2PG allows for such a reaction to occur by forming a high-energy intermediate. The high potential of PEP reflects the large release of energy that occurs with the conversion of enolpyruvate to its keto tautomer, pyruvate

The binding of the regulatory ligands and substrates to the fructose bisphosphate helps in activating pyruvate kinase from Escherichia coli at equilibrium. The allosteric activator called fructose bisphosphate, and the substrate phosphoenolypyruvate binds in a very cooperative manner to the enzyme. There is one site for each of these ligands per monomer. In the presence of fructose bisphosphate the binding of phosphoenolpyruvate follows an absorption isotherm, i.e., all homotropic interactions of the substrate are lost.