Gluconeogenesis Control
GLUCONEOGENESIS CONTROL
MECHANISMS OF REGULATION
- Allosteric regulation
- Hormonal regulation
- Substrate availability
Pyruvate carboxylase
- 2Pyruvate + 2CO2 + 2ATP --> 2Oxaloacetate + 2ADP
- Activated by Acetyl CoA (product of FA breakdown, marker of energy abundance & low blood glucose)
Phosphoenolpyruvate carboxykinase (PEPCK)
- 2Oxaloacetate + 2GTP --> 2Phosphoenolpyruvate (PEP) + 2GDP + 2CO2
Corresponding glycolytic reaction
- Pyruvate kinase: 2PEP + 2ADP --> 2Pyruvate + 2ATP
- Inhibited by Acetyl CoA
Fructose 1,6-bisphosphatase-1 (FBP-1)
- Fructose 1,6-BP + H2O --> Fructose 6-P + Pi
- Activated by Citrate (CAC intermediate & marker of energy abundance)
- Inhibited by AMP (marker of low energy) & fructose 2,6-BP (hormonally regulated)
Corresponding glycolytic reaction
- PFK-1: Fructose 6-P + ATP --> Fructose 1,6-BP + ADP
- Inhibited by Citrate
- Activated by AMP & fructose 2,6-BP
Glucose 6-phosphatase
- Glucose-6-phosphate + H2O --> Glucose + Pi
- Not allosterically regulated because Km >>> [glucose 6-phosphate]
- Substrate level control
Corresponding glycolytic reaction
- Glucokinase: Glucose + ATP --> Glucose 6-phosphate + ADP
- FBP-2 & PFK-2 are hormonally regulated (PFK-2 inactive when phosphorylated)
- High blood glucose = increased Insulin: glucagon ratio = PFK-2 active
- Low blood glucose = decreased insulin: glucagon ratio = PFK-2 phosphorylated & inactive
- INSULIN: promotes glycolysis
- GLUCAGON: promotes gluconeogenesis