Gluconeogenesis: Glucose Synthesis
Gluconeogenesis occurs primarily in the liver (and kidneys during starvation) to maintain blood glucose levels. It essentially bypasses the three irreversible steps of glycolysis.
| Bypass Step | Key Enzyme | Regulatory Note |
|---|---|---|
| Pyruvate to PEP | Pyruvate Carboxylase / PEPCK | Pyruvate Carboxylase is activated by Acetyl-CoA. |
| Fructose-1,6-BP to Fructose-6-P | Fructose-1,6-bisphosphatase | Rate-limiting; inhibited by Fructose-2,6-bisphosphate. |
| G6P to Glucose | Glucose-6-phosphatase | Located in the ER; absent in muscle cells. |
High-Yield Core Realities:
- Energy Demand: Gluconeogenesis is energy-expensive, requiring 4 ATP, 2 GTP, and 2 NADH per glucose molecule.
- Reciprocal Regulation: Fructose-2,6-bisphosphate is the key switch. High levels promote glycolysis (activate PFK-1) and inhibit gluconeogenesis (inhibit Fructose-1,6-bisphosphatase).
- Precursors: Lactate (from muscle), glycerol (from adipose), and glucogenic amino acids (e.g., alanine).