Introduction to Gluconeogenesis

Question 1

Where does gluconeogensis occur?

Answer 1

In the liver and kidney

Question 2

What is the Daily glucose requirement?

Answer 2

• 160g (120g for the brain).
• About 20g in body fluids.
• About 190g stored as glycogen.

Question 3

Glucose can be synthesised from which non-carbohydrate precursors?

Answer 3

• Lactate (exercise)
• alanine (muscle)
• glycerol (fat).

–Ultimately, these are used to make pyruvate which is turned into glucose.

Question 4

What is the purpoe of gluconeogenesis?

Answer 4

–Removal of blood lactate post-exercise

–Formation of glucose from amino acids or glycerol during fasting.

–Important as body has limited capacity to store glucose.

Question 5

Gluconeogenesis Step 1 – Formation of Oxaloacetate

Answer 5

•Carried out by mitochondrial pyruvate carboxylase.

–Uses ATP.

–Enzyme is activated by acetyl CoA.

Question 6

Gluconeogenesis Step 2 – Formation of Malate and Mitochondrial Exit

Answer 6

• Oxaloacetate is converted into malate in the mitochondria.
• Malate exits the mitochondria and is then converted back to oxaloacetate by formation of NADH

Question 7

Gluconeogenesis Step 3– Formation of Phosphoenolpyruvate

Answer 7

•Carried out by phosphoenolpyruvate carboxykinase.

–(Some of this is) cytosolic.

–Uses GTP (ATP and GTP are easily interconverted so this counts as ATP used).

Question 8

Gluconeogenesis Step 4 – Generation of F1,6-BP

Answer 8

•Carried out by phosphoenolpyruvate carboxykinase.

–(Some of this is) cytosolic.

–Uses GTP (ATP and GTP are easily interconverted so this counts as ATP used).

Fructose 1,6-bisphosphate + H2O→Fructose 6-phosphate + P_i

Question 9

Gluconeogenesis Step 5 – Formation of Glucose

Answer 9

• Final step is conversion of glucose 6-phosphate to glucose.
• Enzyme is glucose 6-phosphatase

–Located on the inside of the endoplasmic reticulum.

Question 10

Draw a diagram to compare glycolysis and Gluconeogenesis

Answer 10

Question 11

Draw a table to compare the key differences in Glycolysis vs Gluconeogenesis

Answer 11

Question 12

What is the net reaction of Gluconeogenesis?

Answer 12

2 Pyruvate + 4 ATP + 2 GTP + 2 NADH + 6 H₂O + 2H⁺ →Glucose + 4 ADP + 2 GDP+ 6 P_i + 2NAD+

• Glycolysis generates 2 ATP.
• Gluconeogenesis requires 6 ATP.
• If glycolysis and gluconeogenesis occur at this same time in the liver the net effect is ATP hydrolysis (bad!).