Gluconeogenesis

Question 1

How is lactate converted to glucose?

Answer 1

• CORI CYCLE transports lactate produced in muscle to the liver, where it is converted to glucose and transported back to muscle
• Lactate converted to pyruvate using lactate dehydrogenase and NADH
• Pyruvate is converted to glucose

Question 2

What is the role of gluconeogenesis?

Answer 2

Produce glucose form other metabolites for use by brain and RBC during times of stress or starvation

Question 3

Explain how gluconeogenesis can contribute to hyperglycaemia in patients with type I diabetes

Answer 3

• Type I diabetics are unable to utilise glucose so the intracellular levels of glucose are very low
• This signals the release of anti-insulin hormones such as glucagon, cortisol and adrenaline which stimulate the regulatory enzymes of gluconeogenesis
• Other metabolites are converted to glucose through the pathway and thus the plasma concentrations of glucose increase causing hyperglycaemia

Question 4

What are the 3 main regulatory enzymes of gluconeogenesis?

Answer 4

• Glucose-6-phosphatase
• Fructose-1,6-bisphosphatase
• PEPCK

Question 5

Why can acetyl CoA not be converted to glucose?

Answer 5

• The reaction of converting pyruvate to acetyl CoA involves the loss of CO2
• Therefore the reaction is IRREVERSIBLE

Question 6

What is the main amino acid involved in gluconeogenesis?

Answer 6

Alanine

Question 7

Where does gluconeogenesis take place?

Answer 7

• LIVER

- Kidney cortex (to a lesser extent)

Question 8

How does Alanine enter gluconeogenesis?

Answer 8

• TRANSAMINATION converts Alanine + α-ketoglutarate —-> Glutamate + OXALOACETATE using the enzyme Alanine aminotransferase (ALT)
• Oxaloacetate can be converted to Phosphoenolpyruvate using the enzyme PEPCK

Question 9

How does glycerol enter gluconeogenesis?

Answer 9

• Glycerol obtained from the breakdown of TAGs in the small intestine by hormone sensitive lipase
• Glycerol -> Glycerol phosphate using GLYCEROL KINASE
• Glycerol Phosphate -> DHAP which can enter step 5 of glycolysis by being converted to Glyceraldehyde-3-P

Question 10

How does pyruvate enter gluconeogenesis?

Answer 10

• Converted to oxaloacetate using PYRUVATE CARBOXYLASE, ATP and CO2
• Oxaloacetate is converted to Phosphoenolpyruvate using PEPCK and GTP
• Phosphoenolpyruvate enters the reverse steps of glycolysis

Question 11

Why does von Gierke’s disease only affect liver glycogen?

Answer 11

Deficiency of Glucose-6-phosphatase, which only present in the liver, not muscles

Question 12

Describe how fructose can be used to produce glucose during fasting/starvation

Answer 12

• Fructose converted to Fructose-6-P using FRUCTOKINASE
• Fructose-6-P —> Glyceraldehyde-3-P by cleavage using ALDOLASE
• Glyceraldehyde-3-P enters gluconeogenic pathway to produce glucose

Question 13

How is gluconeogenesis regulated?

Answer 13

• Key regulatory enzymes PEPCK and FRUCTOSE-1,6-BISPHOSPHATASE
• Activated by glucagon/cortisol
• Inhibited by insulin

Question 14

What are the main substrates for gluconeogenesis?

Answer 14

• Lactate
• Glycerol
• Glucogenic amino acids