Regulation of carbohydrate metabolism

Question 1

Irreversible pathways in glycolysis

Answer 1

Glucose to G6P [Hexokinase]

F6P to FBP [PFK-1]

PEP to pyruvate [Pyruvate kinase]

These steps differ in gluconeogenesis

Question 2

Carbon skeletons used in gluconeogenesis

Answer 2

Lactate [glycolysis]

Amino acids [proteins]

Glycerol [lipids]

Question 3

Steps in gluconeogenesis [different from glycolysis]

Answer 3

G6P—> glucose
- G6Pase

F-1, 6-P2——> F6P
- Fruc-1,6-bishophatase

Pyruvate —-> Oxaloacetate
- Pyruvate carboxylate

Question 4

Allosteric inhibition of PFK-1

Answer 4

ATP- indicates high energy levels

High H+

• Indicates a lot of lactate production.
• Prevents further damage from pH.
• In the heart, high H+ is overcome by high AMP, leading to damage.

Question 5

Allosteric activation of PFK-1

Answer 5

AMP

• Indicates ATP levels.
• Competes with ATP
• Can overcome inhibition by H+ at high levels.

Question 6

Nutrient allosteric activator of PFK-1.

Answer 6

F6P
- indicates glucose catabolism

Fruc-2,6-P2

• indicates high F6P metabolism.
• Most potent PFK-1 allosteric activator.

Question 7

Nutrient allosteric inhibitor of PFK-1.

Answer 7

Citrate

- When in excess, indicates TCA cycle overload due to acetyl CoA build up.

Question 8

PFK-2

Answer 8

Enzyme that converts F6P to Fructose-2,6-bisphosphate [Fruc-2,6-P2]

Part of a single tandem enzyme with Fructose-2,6-bisphosphatase.

Question 9

G6-Pase

Answer 9

Enzyme used in gluconeogenesis.

Convertes G6P to glucose.

Question 10

Fructose-1, 6-bisphosphatase

Answer 10

Enzyme used in gluconeogenesis.

Converts Fructose-1, 6-bisphosphate to F6P.

Question 11

Pyruvate carboxylase

Answer 11

Enzyme used in gluconeogenesis.

Converts pyruvate to oxaloacetate.

Question 12

Phosphoenolpyruvate carboxykinase

Answer 12

Enzyme used in gluconeogenesis.

Converts oxaloacetate to PEP

Question 13

Fructose-2,6-bisphosphate

Answer 13

Product made from F6P using PFK-2 [6-phosphofructo-2-kinase]

The most potent allosteric activator of PFK-1.

Most potent inhibitor of fructose-1,6-bisphosphatase.

Not a metabolite- only use to reinforce allosteric control of PFK-1.

Question 14

Control of PFK-1 and F-1,6-BPase

Answer 14

These enzymes are not controlled by hormone regulation.

- Instead the level of F-2,6-BP.

Question 15

Fructose-2,6-Bisphosphatase

Answer 15

Enzyme that facilitates the conversion of Fructose-2,6-Bisphosphate to F6P.

Part of a single tandem enzyme with PFK-2.

Question 16

Regulation of Fructose-2,6-Bisphosphatase

Answer 16

Phosphorylation stimulates its activation.
- Carried out by cAMP activated protein kinase.

• Glucagon stimulates cAMP increase

Activation stimulates gluconeogenesis as F-2,6-BP is converted to F6P.

Question 17

Regulation of PFK-2

Answer 17

Phosphorylation deactivates PFK-2.
- Stimulated by glucagon action which increases cAMP.

Prevents conversion of F6P to F-2,6-BP.

This inhibits PFK-1.

Stimulates gluconeogenesis:
Stimulates F-1,6-BPase.

Question 18

Allosteric action of Acetyl CoA

Answer 18

Allosteric activator of pyruvate carboxylase.
[ Pyruvate to oxaloacetate]

Inhibits pyruvate dehydrogenase.
[Pyruvate to acetyl CoA]

So why Acetyl CoA is high, it favours gluconeogenesis over glycolysis.

Question 19

Glucagon effect on gluconeogenesis

Answer 19

Glucagon stimulates an increase in cAMP, activating cAMPPK.

Therefore it supports gluconeogenesis by:

• Activating Fruc-2,6-BPase.
• Deactivating PFK-2.

Question 20

Inhibitors of hexokinase

Answer 20

G6P

- Feedback inhibition to prevent XS build up of G6P

Question 21

Inhibitors of PFK-1

Answer 21

H+

Citrate

ATP

Question 22

Activators of PFK-1

Answer 22

AMP
- low ATP levels

Fruc-2,6-BP

Question 23

Inhibitors of Fruc-1,6-BPase

Answer 23

ATP

Fruc-2,6-BP

Question 24

Inhibition of pyruvate kinase

Answer 24

Inhibited when it is dephosphorylated.

Inhibited by high ATP levels
- Indicates high energy levels

Question 25

Activators of pyruvate kinase

Answer 25

Activated when phosphorylated. Fruc-1,6-BP also activates allosterically.

Question 26

Activators of Pyruvate carboxylate

Answer 26

Activated by Acetyl-CoA. | - Indicates TCA overload, stimulating gluconeogenesis

Question 27

Urea cycle

Answer 27

Amino acids are transaminated before being converted to make glucose. - Removes ammonia. Ammonia is converted to urea in the liver and excreted by the liver - Produces fumarate which enters the Kreb's cycle. Fumarate is converted to oxolacetate to be used in gluconeogenesis Increase gluconeogenesis = Increase urea synthesis.

Question 28

Difference in F-2,6-BP utilisation in liver and muscle.

Answer 28

Muscle - Uses glucose and glycogen to drive F-2,6-BP production which drives glycolysis. Liver - Glycolysis is inhibited so F-2,6-BP production is inhibited. - Uses glucose from gluconeogenesis and glycogen to maintain blood glucose level.