Gluconeogenesis

1. Pyruvate (or lactate/amino acids) X2 + ATP + CO2→ Oxaloacetate + ADP

• We are starting with the ending material for glycolysis! 

ENZYME: Pyruvate carboxylase *NEW*

Naming: 

• Pyruvate… 

• Carboxylase: an enzyme that adds carbon dioxide. 

→ Input: ATP + CO2

→ Output: ADP

2. Oxaloacetate (or amino acid) X2 + GTP → Phosphoenolpyruvate + GDP + CO2

• This is an intermediate that is not needed in glycolysis  (Reminder: this gets transported out of the mitochondria to the cytosol) 

ENZYME: Phosphoenolpyruvate carboxykinase 

Naming: 

• Phospho: Phosphate

• Enol: double carbon bond C=C

• Pyruvate: precursor to pyruvate

• Carboxy: carbon dioxide (LOSE CO2 molecule) 

• Kinase: transport a phosphate group from a high energy donor (GTP→ GDP) 

Input: GTP, 

Output: GDP, CO2

3. Phosphoenolpyruvate X2 → 2-phosphoglycerate

• This is our first intermediate from glycolysis (from here, the reaction is the same until step 8) 

ENZYME: Enolase

• REMOVES double bond (does the reverse reaction)

4. 2-phosphoglycerate X2 → 3-phosphoglycerate

ENZYME: Phosphoglycerate Mutase

Naming: 

• Phospho: phosphate

• Glycerate: glycerol

• Mutase: isomerase that just moves the phosphate group

*Remember: reverse reaction!* 

5. 3-phosphoglycerate X2 → 1,3-Biphosphoglycerate

ENZYME: Phosphoglycerate kinase

Naming:

Phosphoglycerate: glycerol with phosphate

Kinase: move phosphate group from high energy donor. 

→ Input ATP 

→ Output: ADP

• Remember, we received an ATP from glycolysis, so in this step, we will need to spend an ATP for the reverse reaction. 

6. 1-3-Biphosphateglycerate X2 → GAP

ENZYME: GAP-3-Phosphate dehydrogenase 

Naming: 

GAP: Our next intermediate! 

3-Phosphate: affects the phosphate on carbon 3

Dehydrogenase: reverse reaction→ uses a hydrogen

→ Input: NADH

→ Output: NAD+

7. GAP or Glycerol (if glycerol, needs to be modified to GAP by enzyme triose phosphate isomerase→ much like DHAP) X2 → Fructose-1,6-Bisphosphate

ENZYME: Aldolase 

8. Fructose-1,6-Bisphosphate → Fructose-6-phosphate

*NEW STEP* 

**RATE LIMITING** 

ENZYME: Fructose-1,6-bisphosphatase

Naming: 

This name makes a bit of intuitive sense, as it removes the phosphate (phosphatase is a molecule that cleaves a phosphate) and adds a hydrogen from H20 to this molecule. 

9. Fructose-6-phosphate → Glucose-6-phosphate

ENZYME: Phosphoglucose isomerase

10. Glucose-6-phosphate

*NEW STEP* 

ENZYME: Glucose-6-phosphatase

• Same thing as before! Phosphatase removes a phosphate group! Adds hydrogen instead from water. Note: Located in the ER in liver cells. 

11. Glucose! (Final product) 

To sum it up: 

-We used 4 molecules of ATP and 2 molecules of GTP per glucose (2 ATP and 1 GTP per pyruvate)

- Be careful with this, as you may be asked how much “ATP” was used, which excludes GTP, and how many “ATP equivalents” were used, which would include GTP. 

-2 NADH molecules