Glycogen Synthesis & Regulation

Question 1

Where is glycogen stored?

Answer 1

• Liver for fuel during fasting states

- Muscles for local metabolism

Question 2

Which enzyme acts to synthesise glycogen?

Answer 2

Glycogen synthase!

Question 3

Which enzyme acts to break down glycogen into glucose?

What does this enzyme release glucose as from glycogen?

Answer 3

Glycogen phosphorylase.

Glucose released as: glucose-1-phosphate.

Question 4

Which enzyme converts glucose-1-phosphate (from glycogen breakdown) into glucose-6-phosphate?

Answer 4

Phosphoglucomutase.

NOT hexokinase or glucokinase as with free glucose in the blood, as the glucose is already phosphorylated.

Question 5

What is the chain of events when we eat carbohydrates or proteins that results in glycogen formation?

Answer 5

1) We ingest the food
2) blood glucose levels rise which causes insulin to be released
3) the insulin causes the blood glucose traveling to the liver (via the hepatic portal vein) from the intestines to enter the hepatocytes
4) the insulin results in activated glycogen synthase, which synthesised glycogen

Question 6

What is the process of synthesis of glycogen called?

Answer 6

Glycogenesis.

Question 7

What is the name of the process of breaking down glycogen?

Answer 7

Glycogenolysis.

Question 8

Why is it the case that glucose-6-phosphate from glycogen breakdown in the liver can enter the blood for use by all tissues in the body, yet glucose-6-phosphate in the muscles can not?

Answer 8

Muscle cells lack glucose-6-PHOSPHATASE = the enzyme which hydrolyses glucose-6-phosphate into glucose + Pi. For this reason it can not leave the myocyte and must be used locally only.

Question 9

What do the following enzymes do:

1) kinases
2) phosphorylases
3) phosphotases

Answer 9

1) phosphorylase using ATP
2) hydrolyse using phosphate
3) remove a phosphate

Question 10

Which molecule is needed first in the synthesis of glycogen via glycogenesis?

Answer 10

Glucose-1-phosphate.

Question 11

What does glucose-1-phosphate link with to form the glucose molecule units which are involved in glycogen synthesis?

What is the complex/molecule called?

Which enzyme is involved in this reaction?

Answer 11

Glucose-1-phosphate bonds with UTP to make UDP glucose and PPi (pyrophospate, X1 comes from UTP and X1 from the glucose-1-phosphate).

The enzyme = UDP-glucose pyrophosphotase.

Question 12

What is the name of the primer used for glycogen synthesis?

What is its role?

What does the UDP-glucose attach to on this molecule?

Answer 12

Glycogenin.

Provides an attachment (an OH group) for the first UDP-glucose molecule.

Question 13

How does glycogen synthase work with UDP-glucose?

Answer 13

It binds new UDP-glucose molecules to an existing glycogen chain, removing UDP in the process.

Question 14

Which enzyme is involved in the branching of glycogen chains?

How does this work?

Answer 14

Glycogen branching enzyme.

It cuts a straight chain and re-attaches it as a branch.

Question 15

How is glycogen synthase activated/deactivated?

What enzymes are involved in the process?

Answer 15

Glycogen synthase is active when NOT phosphorylated.

To inactivate it, protein KINASE A + ATP are required to phosphorylate it.

To activate it, protein phosphotase + H2O are required to dephosphorylate it.

Question 16

How does insulin work with respect to glycogen synthase?

Answer 16

It phosphorylates and therefore activates glycogen synthase phosphatase (the dephosphorylating enzyme for glycogen synthase) which as a result activates glycogen synthase and causes glycogenesis.

Question 17

What is the reaction of glygogenolysis?

What are all the molecules/enzymes involved?

Answer 17

Glycogen + glycogen phosphorylase + Pi —> glycogen(n-1) + glucose-1-phosphate.

Question 18

Which enzyme is involved in removing glucose units from a 1,6-glycosidic bond where the glycogen is branched during glycogenolysis?

Answer 18

Glycogen debranching enzyme.

Question 19

How is glycogen phosphorylase activated/deactivated?

What enzymes are involved in the process?

Answer 19

Glycogen phosphorylase is active when it IS phosphorylated.

To activate it, protein KINASE A + ATP are required to phosphorylate it.

To inactivate it, protein phosphotase + H2O are required to dephosphorylate it.

Question 20

Why is it important that glycogen synthase and glycogen phosphorylase are BOTH phosphorylated by protein kinase A?

Answer 20

Because due to them being active in opposing states (one when phosphorylated, one when not) they are stopped from both acting at once.

Question 21

Which hormone activates protein phosphotase?

What is the result of this?

Answer 21

Insulin.

Glycogen synthase = active
Glycogen phosphorylase = inactive

Question 22

Which hormone activates protein kinase A?

What is the result of this?

Answer 22

Glucagon (and to some extent adrenaline).

Glycogen synthase = inactive
Glycogen phosphorylase = active

Question 23

What is important to remember about protein kinase A in these examples?

Answer 23

Increases in PKA do not directly result in the phosphorylation of glycogen synthase and glycogen phosphorylase, is works via the intermediate enzymes:

1) glycogen synthase kinase
2) glycogen phosphorylase kinase

Question 24

How does glucose self regulate?

Answer 24

It binds to glycogen phosphorylase to inhibit it, thereby reducing its own release.

Question 25

How does the muscle use calcium to regulate glycogen breakdown?

Answer 25

When calcium is released from the SR during muscle contraction, it binds with a CALMODULIN on glycogen phosphorylase kinase thereby activating it. This promotes the phosphorylation of glycogen phosphorylase which activates it, promoting glycogen degradation.

Question 26

How can glycogen degradation continue without the need for hormonal control in periods of prolonged exercise?

How can degradation also be stopped non-hormonally?

Answer 26

In prolonged exercise, AMP levels increase.

AMP is an allosteric activator of glycogen phosphorylase which promotes glycogen degradation.

ATP is an allosteric inhibitor, working opposingly via the same mechanism.

Question 27

What is the defective enzyme in the glycogen storage disease McArdle’s disease?

What are it’s symptoms?

Answer 27

Glycogen phosphorylase.

Exercise intolerance.

Question 28

What is the defective enzyme in the glycogen storage disease Pompe’s disease?

What are it’s symptoms?

Answer 28

Lysosomal glycosidase.

Muscle weakness, cardiac failure.

Question 29

What is the defective enzyme in the glycogen storage disease Von Gierke’s disease?

What are it’s symptoms?

Answer 29

Glucose-6-phosphotase.

Enlarged liver and hypoglycaemia.