Glycogen Metabolism I

Question 1

What is the structure of glycogen?

Answer 1

A long chain homopolymer of glucose molecules with branches.

Question 2

How are glucose molecules that compose glycogen linked together?

Answer 2

Linear chains are connected via alpha- 1,4 glycosidic bonds

Branched chains are connected via alpha- 1,6 glycosidic bonds

Question 3

Describe the ends of glycogen chains

Answer 3

Made up of non-reducing ends that contain terminal glucose with an exposed hydroxyl group at Carbon 4

Question 4

What is the purpose of glycogenin?

Answer 4

The reducing ends connect to this

Serves as a primer for glycogen synthesis

Question 5

Glycogen is degraded and extended from the ____ ____ _____

Answer 5

Non-reducing end

Question 6

Where is glycogen stored?

Answer 6

In the liver and muscles

Question 7

What is glycogen stored as?

Answer 7

Granules

Question 8

What are the 2 functions of glycogen?

Answer 8

Liver glycogen- regulates blood glucose levels

Muscle glycogen- provides a reservoir of fuel (glucose) for physical activity

Question 9

What is the purpose of glycogen metabolism?

Answer 9

To regulate storage and release of glucose

Question 10

What are the 3 regulation mechanisms of glycogen?

Answer 10

Allosteric control
Covalent modification- through reversible phosphorylation of key enzymes
Hormonal control

Question 11

What are the 3 key steps of glycogenesis?

Explain the first key step.

Answer 11

1. Trapping and activating glucose
2. Elongation of glycogen primer
3. Branching of glycogen chains
4. Trapping and activation of glucose- Glucokinase/Hexokinase catalyzes glucose to G6P
   - Phosphoglucomutase then reversibly isomerizes G6P to G1P
   - G1P is converted into UDP-Glucose via Uridine diphosphate (UDP)-Glucose Phosphorylase. Note UDP-Glucose is the active form of Glucose

Question 12

What enzyme catalyzes G1P to UDP-Glucose?

Answer 12

UDP-Glucose Phosphorylase

Question 13

What is the rate-limiting enzyme in glycogenesis?

Answer 13

Glycogen Synthase- catalyzes the transfer of glucose from UDP- glucose to the non-reducing end of the glycogen chain. Forms alpha- 1,4 glycosidic bonds between glucose molecules

Question 14

What enzyme catalyzes the branching of glycogen?

Answer 14

Glucosyl (4:6) Transferase

Question 15

Describe the process of glycogen branching.

Answer 15

When the glycogen chain reaches 11 residues, a fragment of the chain (about 7 residues long) is broken off at an alpha- 1,4 link and reattached elsewhere through an alpha- 1,6 link by Glucosyl (4:6) Transferase

Question 16

The new branch point must be at least ___ residues away from the preexisting branch.

Answer 16

4

Question 17

What is the purpose of glycogen branching?

Answer 17

Increases solubility of glycogen
Increases the number of terminal non-reducing ends
Increases rate at which glycogen can be synthesized and degraded

Question 18

What are the enzymes that catalyze the branching of glycogen?

Answer 18

alpha- 1,4 linkage adds glucose polymers by UDP-glucose and Glycogen Synthase (1 non-reducing ends)

Long glucose polymer branches via Glucosyl (4:6) Transferase to catalyze the alpha (1,6)- linkage (2 non-reducing ends)

Question 19

Describe the steps of glycogenesis.

Answer 19

Glucose to G6P via Hexokinase/Glucokinase

G6P to G1P via Phosphoglucomutase (PGM)

G1P to UDP-Glucose via UDP-glucose pyrophosphorylase

UDP-Glucose to linear Glycogen via Glycogen Synthase (GS)- rate limiting steps

Linear Glycogen to branched glycogen via Glucosyl (4:6) Transferase

Question 20

What is the first step of glycogenolysis?

Answer 20

Glycogen break down to release glucose-1 Phosphate

Question 21

What are the 4 key enzymes of glycogenolysis and their functions?

Answer 21

Glycogen Phosphorylase -Catalyzes the cleavage of glycogen (causes linear chain shortening at the non-reducing end)

Phosphoglucomutase -Two to Remodel glycogen remnants (one for the liver and one for muscle)

Glucose 6 Phosphatase -Converts glycogen breakdown product suitable for metabolism

Question 22

What is the rate-limiting enzyme of glycogenolysis?

Answer 22

Glycogen Phosphorylase

Question 23

Glycogen phosphorylase add an ________ and releases a glucose residue as glucose-1 phosphate

Answer 23

Orthophosphate (PO4^3-)

Question 24

Glycogen phosphorylase uses _____ ____ (AKA ______ ___) as a cofactor

Answer 24

Pyridoxal Phosphate

Vitamin B6

Question 25

Phosphorolysis of glucose residues continues till the Glycogen Phosphorylase gets within _ ____ of the _____ _____ of a branch point.

Answer 25

4 residues Alpha- 1,6 linkage

Question 26

Once G1P is released from the linear chain glycogen what catalyzes G1P to G6P?

Answer 26

Phosphoglucomutase

Question 27

Glycogen at this point has 4 glucose molecules attached/branched to a long glucose polymer underneath it. What enzyme catalyzes the release of 3/4 of the glucose molecules on the top strand and adds them to the bottom strand in a linear fashion?

Answer 27

Transferase

Question 28

What enzyme catalyzes the release of the last glucose molecule attached to the linear chain in a branched fashion?

Answer 28

Alpha- 1,6 Glucosidase

Question 29

What is the overall yield of debranching of glycogen?

Answer 29

10 G1P for every 1 glucose the 1 glucose is always the last glucose monomer in the branched chain to be released

Question 30

Can G6P leave the cell?

Answer 30

No! Glucose 6 Phosphate cannot leave the cell. It must first be converted to glucose and then leave. T1- Pulls G6P into the cell T2- Rips phosphate off G6P via G6P phosphatase T3- Pushes glucose out of the cell

Question 31

Which one, the liver or muscle cells, has Glucose 6 Phosphatase?

Answer 31

Liver, converts it to glucose which can be released into the bloodstream Muscle cells do not have glucose 6 phosphatase so G6P stays in the cells

Question 32

Describe lysosomal glycogenolysis. What enzyme is used to catalyze this reaction?

Answer 32

A small amount of glycogenolysis occurs via lysosomal alpha 1,6 glucosidase (AKA acid maltase). Shortens branches of glycogen but does not debranch them. Causes the release of free glucose

Question 33

What is Pompe Disease?

Answer 33

When you do not have sufficient levels of alpha- glucosidase (AKA acid maltase)

Question 34

What is Von Gierke Disease?

Answer 34

Deficiency in Glucose 6 Phosphatase levels, therefore leading to the inability to form free glucose from G6P in the liver

Question 35

During glycogenolysis, G6P is found in both the liver and muscle, but what is the difference when they are in their respective locations?

Answer 35

G6P in the liver is able to become free glucose via glucose 6 phosphatase G6P in muscle can be directly used in glycolysis to form energy for active muscles

Question 36

During glycogenolysis, G1P cannot enter what 2 tissue types and must be converted into what to enter these tissues?

Answer 36

Liver and Muscle G6P via Phosphoglucomutase

Question 37

What is Hers Disease?

Answer 37

The inability to form G1P (for the liver) from Glycogen due to a deficiency in Glycogen Phosphorylase

Question 38

What is McArdle Disease?

Answer 38

The inability to form G1P (for muscles) from Glycogen due to a deficiency in Glycogen Phosphorylase

Question 39

What is Cori Disease?

Answer 39

The inability to release the last glucose molecule attached in a branched fashion to the linear chain below it. Due to the deficiency of the debranching enzyme alpha 1,6- Glucosidase This causes a buildup of glycogen to form.