Gluconeogenesis

Question 1

Define ‘gluconeogenesis’

Answer 1

a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as pyruvate, lactate, glycerol, and glucogenic amino acids

Question 2

In which tissues is gluconeogenesis active?

Answer 2

In the liver, but during prolonged starvation it can also occur in the kidney cortex (but production of pyruvate and lactate can occur in muscle)

Question 3

Under what circumstances will gluconeogenesis occur?

Answer 3

During prolonged exercise or starvation where the glycogen reserves only last for between 12-24 hours, thereafter gluconeogenesis is required to maintain blood glucose levels within safe limits.

Question 4

What are the major precursors for gluconeogenesis (including their tissue origin)?

Answer 4

Glycerol (from triacylglycerol hydrolysis in adipose tissue), lactate (from anaerobic respiration in erythrocytes and active skeletal muscle) and amino acids (from breakdown of muscle protein)

Question 5

In which part(s) of the cell does gluconeogenesis occur?

Answer 5

Cell cytosol, except for the carboxylation of pyruvate, which occurs in the mitochondria.

Question 6

Which 3 enzymes catalyse irreversible reactions in glycolysis?

Answer 6

hexokinase, phosphofructokinase-1 (PFK-1) and pyruvate kinase

Question 7

Outline the process of gluconeogenesis, naming the compounds involved

Answer 7

Pyruvate (lactate and amino acids may contribute) -> oxaloacetate -> malate (malate shuttle transport) -> oxaloacetate -> phosphoenolpyruvate (PEP) -> GAP (or DHAP) -> fructose-1,6-bisphosphate -> fructose-6-phosphate -> glucose-6-phosphate -> glucose

Question 8

List the enzymes involved in gluconeogenesis

Answer 8

Pyruvate carboxylase, maltate dehydrogenase, PEP-carboxylase, fructose-1,6-bisphosphatase, glucose-6-phosphatase

Question 9

What’s the role of pyruvate carboxylase?

Answer 9

To remove carbon dioxide from pyruvate to form oxaloacetate

Question 10

What’s the role of maltate dehydrogenase?

Answer 10

To function as part of the ‘malate shuttle’ pathway, which converts oxaloacetate to malate and back to oxaloacetate again

Question 11

What’s the role of PEP-carboxylase?

Answer 11

This enzyme converts oxaloacetate to phosphoenolpyruvate (PEP) by removing a carbon dioxide group and this requires the hydrolysis of GTP -> GDP + Pi to work

Question 12

What’s the role of fructose-1,6-bisphosphatase

Answer 12

Facilitates the removal of a phosphate group from fructose-1,6-bisphosphate to fructose-6-phosphate through hydrolysis

Question 13

What’s the role of glucose-6-phosphatase?

Answer 13

Facilitates the removal of a phosphate group from glucose-6-phosphate to produce glucose through hydrolysis

Question 14

Why can’t fatty acids be used to make glucose?

Answer 14

Fatty acids are broken down to acetyl CoA which cannot be converted to glucose (as it can’t form oxaloacetate), only the glycerol can be converted

Question 15

How does fatty acid oxidation facilitate gluconeogenesis?

Answer 15

Fatty acids provide energy for the process to occur, and the high levels of acetyl CoA activate pyruvate carboxylase , and the acetyl CoA and NADH produced inhibit the PDC so this will redirect respiration to form lactate and then enter gluconeogenesis in muscle cells etc.

Question 16

What 3 hormones regulate gluconeogenesis?

Answer 16

Insulin, adrenaline, glucagon

Question 17

Why is a ‘malate shuttle’ required to transport oxaloacetate?

Answer 17

Oxaloacetate cannot cross the inner mitochondrial membrane so it is reduced to malate, which is transported into the cytosol where it is re-oxidised,

Question 18

Why is gluconeogenesis excessive in diabetics?

Answer 18

there is an increased supply of precursor molecules e.g. glycerol and amino acids, along with increased levels of fatty acids. In addition, there is an increased glucagon:insulin ratio

Question 19

Define ‘glucogenic amino acids’

Answer 19

If an amino acid can be broken down to produce pyruvate or oxaloacetate (then glucose can be synthesised from the amino acid)

Question 20

Which two amino acids aren’t glucogenic?

Answer 20

leucine and lysine

Question 21

What are the two main glucogenic amino acids?

Answer 21

Glutamine and alanine

Question 22

Define the ‘cori cycle’

Answer 22

the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is metabolized

Question 23

Explain the role of the cori cycle in gluconeogenesis

Answer 23

It produces lactate which can then travel to the liver in the blood and therefore be converted to glucose to increase blood glucose levels.