Gluconeogenesis

The "reverse" of glycolysis

Where does gluconeogenesis typically occur in the body?

The liver

Gluconeogenesis occurs when the body is in a ___ state to maintain blood glucose

Fasted

Substrates of gluconeogenesis

1. Lactate

2. Glycerol

3. Glucogenic Amino Acid

4. Odd chain fatty acid

The 3 irreversible steps gluconeogenesis must overcome:

1. Pyruvate → Phosphoenolpyruvate (Pyruvate Kinase)

2. F-1,6-BP → F-6-P (PFK-1)

3. G-6-P → Glucose (Hexokinase)

Enzyme that overcomes G-6-P → Glucose

Glucose-6-Phosphatase

Found only in the Lumen of the ER of liver/kidney cells

Enzyme that overcomes F-1,6-BP → F-6-P

Fructose-1,6-Bisphosphatase

Rate limiting step

Enzyme that overcomes Pyruvate → Phosphoenolpyruvate

Pyruvate Carboxylase & PEPCK

Requires biotin and ATP/GTP

Occurs partly in the mitochondria

Acetyl-CoA from fat breakdown is an allosteric activator

Energetic cost of gluconeogenesis

1. 4 ATP

2. 2 GTP

3. 2 NADH

Regulators of gluconeogenesis

1. Insulin (Inhibitory)

2. Glucagon (Stimulatory)

3. Cortisol (Stimulatory)

Where does gluconeogenesis occur in the cell?

Cytosol and mitochondria