Gluconeogenesis Reactions
GLUCONEOGENESIS
- Synthesis of glucose from non-carbohydrate precursors
- Occurs mostly in the liver and minor process in kidney
- Kidney produces 10% total glucose during overnight fast
ENZYMES UNIQUE TO GLUCONEOGENESIS
1. Pyruvate carboxylase (mitochondrial matrix)
2. Phosphoenol carboxykinase (cytosolic and mitochondrial isozymes)
3. Fructose 1,6-bisphosphatase (cytosol)
4. Glucose 6-phosphatase (ER membrane-bound)
PEPCK
- Converts oxaloacetate to phosphoenolpyruvate (PEP)
- Consumes 1 GTP and releases 1 CO2
Cytosolic PEPCK
- Used in the malate shuttle: shuttles oxaloacetate from mitochondrion to cytosol via malate
- Pathway dominates when pyruvate is the gluconeogenic substrate
- Mitochondrion: oxaloacetate --> malate (consumes 1 NADH)
- Cytosol: malate --> oxaloacetate (releases 1 NADH)
- Released NADH used in G3P synthesis
- Pyruvate substrate uses cytosolic PEPCK: consumes 2 NADH
Mitochondrial PEPCK
- Pathway dominates when lactate is substrate
- Cytosol: lactate --> pyruvate (releases 1 NADH)
- Released NADH used in G3P synthesis
- Mitochondrial PEPCK: oxaloacetate --> PEP (can cross mitochondrial membranes)
- Lactate substrate uses mitochondrial PEPCK: does NOT consume NADH