Chapter 3 - Glycogen Metabolism

Question 1

What are the 4 reasons as to why GLycogen is stored in the muscles and Liver as an emergency energy source?

Answer 1

1. Enables fast catabolism
2. Can be metabolized anaerobically
3. Glycogen can be easily catabolized in the liver (can’t be done in fatty acids)
4. Large amounts of glucose can be stored without affecting osmolarity.

Question 2

Why is there extensive branching in Glycogen?

Answer 2

So that multiple glycogen phosphorylases can act at several non-reducing ends of Glycogen chains to generate large amounts of Glucose-1-P for glycolysis, or to release glucose in the blood quickly

(essentially, more areas to interact with enable quick and easy catabolism)

Question 3

What three enzymes are involved in glycogen breakdown?

Answer 3

Glycogen Phosphorylase
Glycogen Debranching Enzyme
Phosphoglucomutase

Question 4

What 2 jobs does the Glycogen Debranching Enzyme have?

Answer 4

1. Acts as glycosyltransferase - It transfers an alpha(1,4)-linked trisaccharide unit from the limit branch to the non-reducing end.
2. Also has a separate site for the alpha(1,6)-glucosidase activity, which it hydrolyses the the remaining glucose of the branch, linked by a (1-6) link to the main chain releasing free glucose - not G1P.

Question 5

What 2 ways are the enzymatic activities of Glycogen phosphorylase and glycogen synthase controlled?

Answer 5

Direct allosteric control and covalent modification

Question 6

What are the allosteric inhibitors/activators of Glycogen phosphorylase?

Answer 6

G6P and ATP are allosteric inhibitors whereas AMP is an allosteric activator

Question 7

What is an allosteric activator of GLycogen Synthase?

Answer 7

G6P

Question 8

How do phosphorylase a (phosphorylated form) and phosphorylase b (dephosphorylated form) compare to each other?

Answer 8

Phosphorylase a is more active than phosphorylase b.
Also, phosphorylase a is not affected by inhibition by ATP

Question 9

Why is phosphorylase a not affected by inhibition by ATP?

Answer 9

Needs to be able to make Glycogen in emergency situations quickly.

Question 10

In what instances is the synthesis of Glycogen done?

Answer 10

Emergency situations
-Low glucose (blood sugar)
-In danger and needs to get away quick

Question 11

What 3 enzymes are involved in the phosphorylation of Glycogen phosphorylase?

Answer 11

1. Phosphorylase Kinase
2. c-AMP-dependant protein kinase (cAPK)
3. Phosphoprotein Phosphotase 1

Question 12

What are 3 attributes of cAMP Dependant Protein Kinase (cAPK)

Answer 12

-Requires cAMP for activation
- cAMP binds to the regulatory subunit of the enzyme, releasing TH catalytic units in active form
- The enzyme is a tetramer in inactive form

Question 13

How is phosphorylase kinase maximally activated?

Answer 13

By Ca2+ binding to the delta subunit
Phosphorylation of its alpha, beta, gamma subunits

Question 14

What are Glycogen storage diseases?

Answer 14

They are inherent disorders which are caused by defects in the genes encoding enzymes involved in synthesis and break down of glycogen. There are 10 total

Question 15

what do defects in liver enzymes typically cause? How are they different to muscle enzymes?

Answer 15

They typically cause hepatomegaly (enlarged liver) and hypoglycemia, whereas those in muscles typically just cause muscle cramps.

Question 16

What does Von Gierke’s disease involve? (Type 1 Glycogen storage disease)

Answer 16

It is a Glucose-6-phosphatase deficiency. This enzyme allows for the release of glucose in the blood, without it, glucose cannot be easily released which causes hypoglycemia to occur.
There is a large buildup of Glycogen in the liver which causes inflammation in the liver (hepatomegaly)

Question 17

What treatments are there for Von Gierke’s disease?

Answer 17

Inhibition of glucose uptake by drugs,
Continued intra-gastric feeding during the night
Liver transplant

Question 18

What is Her’s Disease? (Type 6 Glycogen Storage Disease)

Answer 18

Liver Phosphorylase Deficiency. Patients are unable to use Liver glycogen. aka, they cant break down glycogen, which results in similar symptoms to Von Gierkes disease:
- hypoglycemia
hepatomegaly (liver inflammation)

Question 19

How do you treat Her’s disease?

Answer 19

Inhibition of glucose uptake by drugs
continued intra-gastric feeding during the night
Liver transplant

Question 20

What is Anderson’s Disease? (Type 4 Glycogen Storage Disease)

Answer 20

Branching Enzyme Deficiency. Without this enzyme, long, unbranched chains of glucose are produced, which cannot be easily broken down and cause severe liver malfunction. The glucose produced acts like a starch and the immune system treats it as a foreign entity and attacks the liver.
Symptoms include:
Painful inflammation of the Liver
Liver failure
Liver damage (due to immune system attacking liver)
Death to patient within 4 years of age.

Question 21

How do you treat Anderson’s disease?

Answer 21

Liver transplant

Question 22

What is type 0 GLycogen Storage disease?

Answer 22

Liver Glycogen Synthase Deficiency.
The only disease of glycogen metabolism where there is a deficiency of glycogen.
Symptoms include:
Hyperglycemia after meals and Hypoglycemia at other times.
Essentially, blood sugar levels are not regulated.

Question 23

What is McArdle’s Disease (Type 5 Glycogen Storage disease)

Answer 23

Muscle Phosphorylase Deficiency.
Blood glucose is unaffected.
Symptoms arise in adulthood and include severe muscle cramps after strenuous exercise.
This can be avoided by doing less-strenuous exercises.