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Pyruvate Kinase
PYRUVATE KINASE
- Last enzyme in glycolysis
- Irreversibly dephosphorylates phosphoenolpyruvate (PEP) to form pyruvate
- 1 ATP produced by substrate level phosphorylation
- Several isozymes: M-type (muscle) and L-type (liver)
- All isozymes allosterically regulated (L-type also hormonally regulated)
Allosteric regulation
Activation
- AMP: marker of ATP depletion or low energy
- Fructose 1,6-bisphosphate: product of rate-limiting reaction in glycolysis
Inhibition
- ATP: sufficient energy
- Acetyl CoA: first intermediate of citric acid cycle
- Alanine: can be produced from pyruvate; sufficient pyruvate in the cell
- Allosteric and hormonal regulation (similar to PFK-2)
Hormonal regulation
Activation
- Insulin activates phosphatases, which remove phosphate from PK
- Makes PK susceptible to positive allosteric regulators
Inhibition
- Glucagon promotes phosphorylation of PK via cAMP-dependent pathway
- Makes PK susceptible to negative allosteric regulators
Pyruvate kinase deficiency
- Produce hemolytic anemia (spiculated RBC's)
- RBC biconcave shape maintained by sodium-potassium pumps (require ATP)
- RBC's do not have mitochondria: rely on glycolysis for ATP