Regulation of gluconeogenesis

Question 1

Explain Gluconeogenesis ?

Answer 1

De novo glucose synthesis from non-carbohydrate precursors in liver and kidney

e. g.
- glycerol from fat metabolism
- lactate from red blood cells
- alanine from protein breakdown

Question 2

What does Gluconeogenesis maintain ?

Answer 2

Maintains blood glucose during fasting, starvation or when glycogen reserves are
depleted to maintain brain function and RBCs

Question 3

What can mammals not convert?

Answer 3

Fatty acids to sugar

Question 4

Where does Glycolysis occur mainly in compared to Gluconeogenesis ?

Answer 4

• Glycolysis occurs mainly in the muscle and brain

- Gluconeogenesis occurs mainly in the liver

Question 5

Where does the first gluconeogenic steps occur ?

Answer 5

The first gluconeogenic steps occur in the mitochondria: the inner mitochondrial membrane is permeable to pyruvate and PEP but not oxaloacetate

Question 6

Short term stimulation of gluconeogenesis ?

Answer 6

By glucagon and adrenaline by changes in protein phosphorylation or mobilisation of fatty acids and production of acetyl CoA

Question 7

Long term stimulation of gluconeogenesis ?

Answer 7

• Occurs through enzyme induction by glucagon, glucocorticoids and thyroid hormones, e.g pyruvate carboxylase,phosphoenolpyruvate carboxykinase, fructose-1,6 bisphosphatase and glucose-6-phosphatase

Question 8

What inhibits gluconeogenesis?

Answer 8

Inhibited acutely by insulin via dephosphorylation and suppression of lipolysis and in the long term by suppression of gluconeogenic enzymes.

Question 9

Irreversible steps of gluconeogensis ?

Answer 9

• Pyruvate carboxylase converts pyruvate to oxaloacetate
• Phosphoenolpyruvate carboxykinase (PEPCK)
  converts oxaloacetate to
  phosphoenolpyruvate (PEP)
• Fructose-1,6-bisphosphatase converts F-1,6BP to F6P
• Glucose-6-phosphatase converts G6P to glucose

Question 10

Formation of PEP (phosphoenolpyruvate) from pyruvate ?

Answer 10

• The formation of phosphoenolpyruvate from pyruvate requires two energy-consuming steps, catalysed by pyruvate carboxylase and phosphoenolpyruvate carboxykinase (PEPCK)

Question 11

Explain the first conversion using Pyruvate carboxylase ?

Answer 11

• Converts pyruvate to oxaloacetate
• carboxylation using a biotin cofactor
• requires transport into the mitochondria

Question 12

Explain the second conversion using PEPCK ?

Answer 12

• Converts oxaloacetate to PEP
• Phosphorylation from GTP and decarboxylation
• Occurs in mitochondria or cytosol depending on the organism

Question 13

Conversion of pyruvate to acetyl CoA ?

Answer 13

• Catalysed by the pyruvate dehydrogenase complex (E1, E2, E3 enzymes) and requires 5
  coenzymes:
  – TPP, lipoyllysine, and FAD are prosthetic groups
  – NAD+ and CoA-SH are co-substrates
  – 5 step process

Question 14

Where are both PDH and pyruvate carboxylase found ?

Answer 14

Mitochondrial matrix