Gluconeogenesis

gluconeogenesis
  • Pyruvate carboxylase: Pyruvate → Oxaloacetate
    • Biotin as prosthetic group for the carboxyl group transfer.
    • Avidin, found in raw egg whites, binds biotin and inhibit its intestinal absorption.
    • Activated by acetyl-CoA.
    • ATP hydrolysis.
    • Oxaloacetate transported out of mitochondria as aspartate by shuttle.
  • PEP Carboxykinase: Oxaloacetate → PEP
    • GTP hydrolysis and decarboxylation drives reaction.
  • Fructose bisphosphatase: F1,6BP → F6P
    • Inhibited by F2,6P (which stimulates glycolysis).
    • Activated by ATP, citrate
    • High blood glucose: insulin released by pancreas, dephosphorylates PFK-2/FBP-2 to make PFK-2 active, ↑ F2,6P, glycolysis occurs.
    • Low blood glucose: glucagon released by pancreas, phosphorylates PFK-2/FBP-2 to make FBP-2 active, ↓ F2,6P, gluconeogenesis occurs. In muscles, epinephrine causes phosphorylation of PFK2/FBP2 causes PFK2 to be active, which makes F2,6BP and activates glycolysis.
    • Main regulatory step.
  • Glucose-6-phosphatase: G6P → Glucose
    • Found only in liver, so gluconeogenesis in liver produces blood glucose.
  • Deficiency of gluconeogenesis causes hypoglycemia.
  • What feeds into gluconeogenesis: lactate (Cori cycle by lactate DH), amino acids (citric acid cycle), glycerol (fat).
  • Occurs in the liver when blood sugar is low (fasting)