Gluconeogenesis

Question 1

What is Gluconeogenesis

Answer 1

the formation of glucose from non-carbohydrate sources

Question 2

When does Gluconeogenesis occur?

Answer 2

periods of starvation and exercise

Question 3

Where does Gluconeogenesis occur?

Answer 3

mainly in liver and smaller extent in cortex of the kidney

Question 4

What is needed for Gluconeogenesis to occur?

Answer 4

Requires ATP

Source of carbon

Question 5

Sources of carbon for Gluconeogenesis?

Answer 5

1. Lactate from muscle (glycolysis)
2. Glycerol from fat breakdown (lipolysis)
3. Amino acids from proteolysis

Question 6

Sources of energy for Gluconeogenesis?

Answer 6

1. ATP – from glycolysis and Krebs cycle

2. Fatty acids -broken down to supply ATP

Question 7

What is the most common starting material for Gluconeogenesis? Why?

Answer 7

Pyruvate

It is the reversal of glycolysis

Question 8

3 irreversible steps of glycolysis

Answer 8

1: G6P —> glucose : glucose-6-phosphatase
2: F1,6BP —> F6P: fructose-1,6-bisphosphatase
3: pyruvate —> PEP: more complicated

Question 9

Intermediates needed to obtain pyruvate from from phoshoenolpyruvate (PEP)

Answer 9

Malate cycle-

• Oxaloacetate (lacks transporters in the mitochondria)
• Malate (can be transported out of mitochondria)

-Require 1 ATP and 1 GTP molecule

Question 10

How does fat contribute to Gluconeogenesis?

Answer 10

Fats are made from glycerol backbone and 3 fatty acid side chains.
Glycerol can be used to make pyruvate which is used in Gluconeogenesis
Fats can also make acetyl co-A which is used to generate ATP to be used in Gluconeogenesis

Question 11

Enzymes regulated by Acetyl co-A

Answer 11

Activates pyruvate carboxylase (PC)

Inhibits pyruvate dehydrogenase complex (PDC)

Question 12

What is the mechanism of Gluconeogenesis during fasting and excercise

Answer 12

In muscle: Glucose produces lactate during anaerobic conditions.
Lactate in liver is oxidized back to glucose by gluconeogenesis
Glucose sent back to muscle to do work – no net synthesis of glucose.

Interaction between muscle and liver called the Cori Cycle.
During fasting same process of gluconeogenesis occurs to maintain constant glucose levels.

Question 13

What is needed for the cory sycle to function?

Answer 13

Cori cycle only works if you conserve pyruvate and avoid its conversion to acetyl co-A.
Fatty acid metabolism: produces acetyl co-A which inhibits the function of the PDC (enzyme complex that converts pyruvate to acetyl co-A to enter the Kreb’s cycle)

Question 14

What are the 2 main functions of fat in gluconeogenesis?

Answer 14

1. Supply the energy

2. Prevent conversion of pyruvate to acetyl-co-A

Question 15

Mechanism of Gluconeogenesis from glycerol

Answer 15

Glycerol produced from triglyceride break down.

Glycerol the converted into dihydroxyacetone phosphate only in liver and kidneys

Question 16

Mechanism of Gluconeogenesis from amino acids

Answer 16

Mostly in muscle, proteins are broken own (proteolysis) into amino acids that can feed to different stages of gluconeogenesis.

Question 17

Which amino acids undergo Gluconeogenesis?

Answer 17

alanine and glutamine.

Question 18

How does Glucogenic AA and Ketogenic AA affect Gluconeogenesis?

Answer 18

Glucogenic AA can provide carbons to gluconeogenesis

Ketogenic AA (lysine and leucine) cannot provide carbons, but can be used in fatty acid metabolism to produce energy for gluconeogenesis.

Question 19

Describe the hormonal control produce of gluconeogenesis.

Answer 19

Glucagon and adrenaline- promote gluconeogenesis Insulin- inhibits gluconeogenesis and promotes glycolysis.

Cortisol -also promotes gluconeogenesis.

Question 20

Describe when gluconeogenesis goes wrong

Answer 20

Inborn errors of gluconeogenesis alter the function of each of the four enzymes that regulate gluconeogenesis.
Symptoms occur due to the build up of acetyl co-A (ketosis), lactate (acidosis) and hypoglycaemia (low glucose levels).
Can cause seizures, coma, hyperventilation, apnea and death!
Complicates diabetes!