• 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)

M-TYPE ISOZYMES

Allosteric regulation

Activation

• AMP: marker of ATP depletion or low energy
• Fructose 1,6-bisphosphate: product of rate-limiting reaction in glycolysis
  (feed-forward activation: stimulates downstream glycolytic enzymes)

Inhibition

• ATP: sufficient energy
• Acetyl CoA: first intermediate of citric acid cycle
• Alanine: can be produced from pyruvate; sufficient pyruvate in the cell

L-TYPE ISOZYME

• 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

CLINICAL CORRELATION

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