Glycogen 1 And 2

Question 1

What is glycogen?

Answer 1

• Storage polysaccharide with glucose as the monomeric unit
• highly branched storage form of glucose
• in a form that can be rapidly mobilized
• when required as a ready source of energy

Question 2

Where is glycogen located?

Answer 2

• Glycogen is found in the cytosol in granules associated with enzymes that synthesize and degrade it
• Major concentrations found in skeletal muscle and liver

Question 3

What is liver glucose is used for?

Answer 3

Liver glucose is a source of glucose units for maintaining blood glucose level: 6-10% of wet weight

Question 4

What is muscle glycogen used for?

Answer 4

A source of glucose units for use by muscle itself (“selfish”): 1-2% of wet weight

Question 5

What causes fluctuation in glycogen stores?

Answer 5

• Glycogenesis- synthesis of glycogen. Occurs in a well fed state
• Glycogenolysis- this is the degradation of glycogen. Occurs in a fasting state

Question 6

How are liver glycogen and muscle glycogen affected by fasting and well fed states?

Answer 6

• Liver glycogen increases during well-fed states and decreases during a fast
• Muscle glycogen not affected in short fasts(few days) and only moderately in long fasts(week)

Question 7

What are the five phases of glucose homeostasis?

Answer 7

1. Absorptive phase
2. Post absorptive phase
3. Early starvation
4. Intermediate starvation
5. Prolonged starvation

Question 8

What stage does glucose homeostasis does gluconeogenesis occur?

Answer 8

Early starvation

Question 9

Why can’t fat be used as a rapid energy source such as Glycogen ?

Answer 9

• Fat can’t be mobilized as rapidly in skeletal muscle as glycogen
• Fat can’t be oxidizednto produce energy in the absence of oxygen
• Beta-oxidation requires energy input
• The carbon atoms of fatty acids can’t be used by any other pathway in order to provide energy for use by tissues such as brain and erythrocytes

Question 10

Describe the structure of glycogen

Answer 10

• Branched Chain homopolysaccharide of a-D-Glucose
• a-1,4 glycosidic linkages predominate
• a-1,6 glycosidic linkages form the branches, after every 8-10 glycosyl residues
• Branches occur more frequently in the center and less frequently in the periphery of the molecule
• the anomeric carbon that is not attached to another glucosyl residue (i.e. reducing end) is attached to a protein called glycogenin by a glycosidic bond

Question 11

What is the purpose of branching in Glycogen?

Answer 11

• Provides many non-reducing ends- many enzymes can work on the molecule at the same time- speeds synthesis and degradation
• Branching increases solubility of glycogen - the more irregular the molecule, the less likely it is to crystallize and precipitate

Question 12

When is glycogen synthesized?

Answer 12

Glycogen synthesized when blood glucose levels are high e.g. during and after a meal

Question 13

Explain the beginning of glycogen synthesis

Answer 13

• A primer is required to initiate glycogen synthesis
• A pre-existing glycogen molecule of the protein “glycogenin” serves as the primer
• Glycogenin is self-glucosylating, attaches glucose for UDP-glucosebto tyrosine residue
• This then serves as template for glycogen synthase

Question 14

How is UDP-glucose synthesized?

Answer 14

• UDP glucose synthesized from glucose 1-P and UTP by UDP-glucose pyrophosphorylase
• PPi is also produced
• PPi —> 2Pi by pyrophosphatase. This drives both reactions in the forward direction

Question 15

What is UDP-glucose and it’s function?

Answer 15

UDP-glucose is a high energy compound that can donate glycosyl units to the growing glycogen chain
-No further energy is required for glycogen synthesis

-The UDP released can be converted back to UTP by nucleoside diphosphate kinase

UDP + ATP —>(goes in reverse as well)

Question 16

Explain the function of phosphoglucomutase

Answer 16

Interconversion of glucose 6-phosphate and glucose 1-phosphomutase

1. Phosphoglucomutase -P donates phosphate to glucose-6-P to make glucose-1,6-P
2. Phosphoglucomutase converts glucose-1,6-P. To glucose-1-P and phosphoglucomutase P

Reverse also happens

1. Phosphoglucomutase-P converts glucose 1-P to phosphoglucomutase and glucose-1,6-P
2. Phosphoglucomutase converts glucose-1,6-P to glucose 6-P and phosphoglucomutase-P

Question 17

Explain the glycogen synthase mechanism

Answer 17

• Glucose units from UDP-glucose are added onto the non-reducing ends of glycogen in a reaction Catalyzed by glycogen synthase
• this is a rate limiting step in glycogen synthase
• Glycogen synthase is only able to Catalyze the formation of a-1,4 glycosidic bonds -resulting in elongation of glycogen chains

Question 18

Give the formula of the glycogen synthase mechanism

Answer 18

-(glycogen)n + UDP-glucose —> (glycogen)n+1 + UDP

Question 19

Explain the glycogen branching

Answer 19

• Branches made by “branching enzyme” : amylo-(a-1,4 —> a-1,6) transglucosidase (common name: glucosyl a-4:6transferase)
• Transfers about 7 glucosyl residues from the non-reducing end to a branch at an adjacent branch point

Question 20

Summarize glycogenesis

Answer 20

1. Glycogenin is glucosylated on the hydroxyl of a tyrosine residue
2. Glycogen synthase elongates chain by forming new a 1 —> 4 linkages
3. Branching enzyme creates new a 1 —> 6 linkages
4. Glycogen synthase elongates branches

Question 21

What enzymes are involved in glycogenolysis ?

Answer 21

Glycogen phosphorylase

Glucosyl a-4,4 transferase

Amylo a-1,6 glucosidase

Debranching enzymes-
Glucosyl a-4,4 transferase

Amylo a-1,6 glucosidase

Question 22

What continuously degrades glycogen?

Answer 22

-Small amount of glycogen continuously degraded by lysosomal enzyme a-1,4-glucosidase (acid maltase)

Question 23

What is Mcardle syndrome?

Answer 23

Skeletal muscle glycogen phosphorylase or Myophosphorylase deficiency)

• Skeletal muscle affected; liver enzyme normal
• Temporary weakness and cramping of skeletal muscle after exercise
• No rise in blood lactate during strenuous exercise
• Normal mental development
• Myoglobinemia and myoglobinuria
• relatively benign, chronic condition
• High levels of glycogen with normal structure in muscle

Question 24

What is Pompe disease?

Answer 24

(Lysosomal a(1,4) glucosidase deficiency )
-Inborn lysosomal enzyme defect

• Generalized (primarily liver, heart and muscle)
• Excessive glycogen concentrations found in abnormal vacuoles in the lysosomes
• Normal blood sugar levels
• Massive cardiomegaly
• Enzyme replacement therapy available
• Infantile form: early death typically from heart failure
• Normal glycogen structure

Question 25

Explain the shortening of glycogen chains

Answer 25

Shortening chains

• Glycogen phosphorylase cleaves a-1,4 glycosidic bonds at non reducing ends leaving 4 glucosyl residues before the branch point using pyridoxal phosphate as a coenzyme
• The resulting structure is called limit dextrin and cannot be degraded by glycogen phosphorylase any further
• Glycogen phosphorylase cannot cleave a-(1,6) glycosidic bonds