Lecture 22: Glycogen Metabolism I

Question 1

Non-reducing ends of glycogen contain

Answer 1

Terminal glucose with free hydroxyl group at carbon 4

Question 2

Reducing ends of glycogen contain

Answer 2

Glucose monomer connected to glycogenin

Question 3

What serves as primer for glycogen synthesis

Answer 3

Glycogenin

Question 4

Glycogen is degraded/extended from what end

Answer 4

Non-reducing end

Question 5

What is the rate limiting step in the formation of glycogen

Answer 5

Transfer of glucose from UDP-glucose to non reducing end of glycogen chain.
Catalyzed by glycogen synthase

Question 6

When does glycogen start branching

Answer 6

After the chain reaches 11 residues, a fragment (about 7 residues long) is broken off and reattached somewhere else through a-1,6 linkage
-New branch point must be at least 4 residues away from preexisting branch

Question 7

What is the point of glycogen branching

Answer 7

Increases solubility of glycogen and increases rate at which glycogen can be synthesized and degraded

Question 8

What is the name of the branching enzyme

Answer 8

Glucosyl 4:6 transferase

Question 9

What is the rate limiting step in the breakdown of glycogen

Answer 9

Glycogen –> glucose-1-phosphate catalyzed by glycogen phosphorylase

Question 10

How does glycogen phosphorylase work to break down glycogen

Answer 10

It adds an orthophosphate and releases a glucose reside as G1P

Question 11

What is the cofactor for glycogen phosphorylase

Answer 11

Pyridoxal phosphate (vitamin B6)

Question 12

When does glycogen phosphorylase stop breaking off glucose residues

Answer 12

Once it gets within 4 resides of the a-1,6 linkage of a branch point

Question 13

How do the remaining 4 glucoses get released from the branch

Answer 13

Transferase transfers 3/4 to the non reducing end of the main chain
Debranching enzyme a-1,6 glucosidase cleaves the a-1,6 bond and releases final glucose

Question 14

Where is glucose-6-phosphatase located

Answer 14

Only in the liver

Therefor G6P is trapped in muscle but not liver

Question 15

Glycogen synthase and glycogen phosphorylase are activated or inactivated by phosphorylation

Answer 15

Glycogen synthase Inactivated by phosphorylation

Glycogen phosphorylase activated by phosphorylation

Question 16

Glycogen synthase is phosphorylated by ___ which is under the control of

Answer 16

Glycogen synthase kinase GSK, which is under the control of insulin and PKA

Question 17

Glycogen phosphorylase state in liver vs muscle

Answer 17

Active R state in liver

Inactive T state in muscle

Question 18

How many ATPs does it take to phosphorylate glycogen phosphorylase

Answer 18

2 ATP

Question 19

Regulation of liver glycogen phosphorylase

Answer 19

Inactivated by free glucose in liver (stabilizes T state), unaffected by AMP in liver

Question 20

Regulation of muscle glycogen phosphorylase

Answer 20

Allosterically activated by AMP (stabilizes R state)

Question 21

Mutation in liver GP causes

Mutation in muscle GP causes

Answer 21

Hers disease in liver

McArdle syndrome in muscle

Question 22

Negative regulators of GP in muscle

Answer 22

ATP and glucose 6 phosphate

Question 23

Type 2 diabetes caused by

Answer 23

Reduced sensitivity to insulin

Down regulation of insulin receptor because of elevated insulin

Question 24

Diabetes glucose level

Answer 24

> 126 mg/dl fasting

>199 mg/dl fed

Question 25

In low fed state, muscle and liver are acted on by

Answer 25

Glucagon - liver
Epinephrine - muscle
Both signal glycogen breakdown

Question 26

Glucagon and insulin are released by

Answer 26

Glucagon- alpha cells of pancreas

Insulin- beta cells of pancreas

Question 27

PKA activated and does what

Answer 27

Phosphorylates Glycogen synthase to inactivate
Phoshphorylates PK
Phosphorylates inhibitor which inhibits PP1

Question 28

Phosphorylated PK does what

Answer 28

Phosphorylates glycogen phosphorylase to activate

Question 29

Allosteric regulator of glycogen phosphorylase kinase (PK)

Answer 29

Ca+ is a positive regulator

Question 30

G6P affect on glycogen synthase and glycogen phosphorylase

Answer 30

G6P activates glycogen synthase and deactivates phosphorylase

Question 31

Fate of G1P in liver vs muscle

Answer 31

In liver it is converted to G6P then to glucose

In muscle there is no G6P phosphatase so it is used in glycolysis or TCA

Question 32

What is the glucose sensor in liver cells

Answer 32

Glycogen phosphorylase

Question 33

GSD 0

Answer 33

Deficiency in glycogen synthase

Rely on glucose in diet

Question 34

GSD III/Cori disease

Answer 34

Deficiency in a-1, 6-glucosidase (debranching enzyme)

Patients have glycogen molecules with large number of short branches

Question 35

GSD IV/Andersen disease

Answer 35

Deficiency in glucosyl 4:6 transferase branching enzyme
Long chain glycogen with fewer branches
Enlargement of liver/spleen, death within 5 years

Question 36

GSD V/ McArdle disease

Answer 36

Deficiency in muscle glycogen phosphorylase
Patients unable to supply muscle with enough glucose
Exercise intolerance

Question 37

GSD VI/ Hers disease

Answer 37

Deficiency in liver glycogen phosphorylase
Low blood glucose levels
Glycogen accumulates in liver - hepatomegaly

Question 38

GSD II/ Pompe disease

Answer 38

Defect in acid maltase (a-glucosidase) used in lysosomal glycogen degradation
Disrupts muscle/liver cell function
Muscle weakness/ heart failure
Recombinant a-glucosidase delivered intravenous for treatment