Gluconeogenesis — four dedicated enzymes + seven glycolysis cards in reverse
Glucose is rebuilt from pyruvate. Four unique pages bypass the irreversible glycolytic steps (hexokinase, PFK-1, pyruvate kinase). The other seven cards are the same glycolysis simulators, not copies — they keep the forward equation; read them backward. Net cost per glucose: 4 ATP + 2 GTP + 2 NADH (PC 2 ATP · PEPCK 2 GTP · PGK reverse 2 ATP · GAPDH reverse 2 NADH).
Pyruvate carboxylase PC · CT half
Pyruvate + ATP + HCO₃⁻ → OAA + ADP + Pᵢ
Mitochondrial committed step. This page is carboxyl transfer onto pyruvate C3. The biotin-carboxylase half (ATP + HCO₃⁻) is named, not drawn. Bypasses pyruvate kinase.
EC 6.4.1.1 · PDB 3BG3
▶ OPEN SIMULATORPEP carboxykinase PEPCK-C · PCK1
OAA + GTP analog → PEP + CO₂ + GDP
Cytosolic PCK1 decarboxylates oxaloacetate then phosphorylates the enolate. Frame holds a GTP analog (GCP), not GTP. Bypasses pyruvate kinase with PC.
EC 4.1.1.32 · PDB 1KHB
▶ OPEN SIMULATOREnolase
2PG ⇌ PEP + H₂O
Same page as glycolysis step 9. The card equation is the forward reaction — gluconeogenesis reads PEP → 2PG.
EC 4.2.1.11
▶ OPEN SIMULATORPhosphoglycerate mutase (PGAM)
3PG ⇌ 2PG
Same page as glycolysis step 8. Forward equation on the card; gluconeogenesis reads 2PG → 3PG.
EC 5.4.2.11
▶ OPEN SIMULATORPhosphoglycerate kinase (PGK)
1,3-BPG + ADP ⇌ 3PG + ATP
Same page as glycolysis step 7. Reverse consumes ATP (2 ATP per glucose).
EC 2.7.2.3
▶ OPEN SIMULATORGAPDH
G3P + Pᵢ + NAD⁺ ⇌ 1,3-BPG + NADH
Same page as glycolysis step 6. Reverse consumes NADH (2 NADH per glucose).
EC 1.2.1.12
▶ OPEN SIMULATORTriosephosphate isomerase (TPI)
DHAP ⇌ G3P
Same page as glycolysis step 5. Supplies DHAP for the aldolase condensation.
EC 5.3.1.1
▶ OPEN SIMULATORAldolase (class I)
F1,6BP ⇌ DHAP + G3P
Same page as glycolysis step 4. Reverse is the aldol condensation to F1,6BP.
EC 4.1.2.13
▶ OPEN SIMULATORFructose-1,6-bisphosphatase FBPase-1 · FBP1
F1,6BP + H₂O → F6P + Pᵢ
Metal-OH hydrolysis of the C1-phosphate. Bypasses PFK-1. AMP allostery is named, not this pocket.
EC 3.1.3.11 · PDB 5LDZ
▶ OPEN SIMULATORPhosphoglucose isomerase (PGI)
G6P ⇌ F6P
Same page as glycolysis step 2. Gluconeogenesis reads F6P → G6P.
EC 5.3.1.9
▶ OPEN SIMULATORGlucose-6-phosphatase G6PC1
G6P + H₂O → glucose + Pᵢ
ER-lumen histidine phosphatase. His176 forms E~P; free glucose leaves. Bypasses hexokinase. Last committed gluconeogenic step.
EC 3.1.3.9 · PDB 9JTM
▶ OPEN SIMULATOR| Glycolysis (irreversible) | Gluconeogenesis bypass |
|---|---|
| Hexokinase · glucose → G6P | G6Pase · G6P → glucose |
| PFK-1 · F6P → F1,6BP | FBPase · F1,6BP → F6P |
| Pyruvate kinase · PEP → pyruvate | PC + PEPCK · pyruvate → OAA → PEP |