Glycogen

Question 1

What are the 4 steps for Glycogen synthesis from glucose-6-phosphate?

Answer 1

G6P
-> Glucose-1-phosphate 
(UDP-glucose pyrophosphorylase) + UTP
-> UDP-Glucose 
(Glycogen Synthase)
-> Unbranched Glycogen 
(Branching enzyme)
-> Branched Glycogen

Question 2

What enzyme causes branhced glycogen to become unbranched?

Answer 2

Debranching enzyme

Question 3

What enzyme breaks down Unbranched Glycogen into Glucose-1-phosphate?

Answer 3

Glycogen phosphorylase

Question 4

What enzyme converts Glucose-6-phosphate to glucose?

Answer 4

Glucose-6-Phosphatase

Question 5

Where is Glucose-6-Phosphatase found?

Answer 5

Liver

Question 6

What enzyme breaks down unbranched glycogen into glucose and is found in lysosomes?

Answer 6

alpha1,4 glucosidase

Question 7

What does glycogen phosphorylase do?

Answer 7

• Removes glucose molecules from glycogen polymer
• Creates glucose-1-phosphate from unbranched glycogen
• Stops when glycogen branches decreased to 2-4 linked glucose molecules (limit dextrins)

Question 8

What vitamin stabilises glycogen phosphorylase?

Answer 8

Vitamin B6

Question 9

What enzyme phosphorylates glycogen phosphorylase?

Answer 9

Glucagon (and epinephrine)

• Becomes more active
• More glucose

Question 10

How do glucagon and insulin glycogen and glucose levels?

Answer 10

Through phosphorylating enzymes - glucagon

Through dephosphorylation (insulin)

Question 11

What are the 2 enzymes which glucagon and epinephrine phosphorylate?

Answer 11

• Glycogen phosphorylase (increasing its activity)

- Glycogen synthase (decreasing its activity)

Question 12

What is the effect of phosphorylation on glycogen phosphorylase’s activity?

(Glucagon and epinephrine phosphorylate glycogen phosphorylase)

Answer 12

Increases activity, more glycogen -> Glucose

Question 13

What is the effect of phosphorylation on glycogen synthase’s activity?

(Glucagon and epinephrine phosphorylate glycogen synthase)

Answer 13

Decreases its activity

• less glycogen made from glucose

Question 14

What enzymes are dephosphorylated by insulin?

Answer 14

• Glycogen phosphorylase (decreased activity - less glucose produced)
• Glycogen synthase (increased activity - more glycogen produced)

Question 15

Describe the pathway inside the cell how epinephrine and glucagon work to activate glycogen phosphorylase?

Same process with glycogen synthase

Answer 15

• Both bind to surface receptors
• Activate Adenyl Cyclase
• Raises cAMP
• Activate protein kinase A
• Phosphorylates intermediatw known as Glycogen phosphokinase A
• Glycogen phosphokinase A then phosphorylates glycogen phosphorylase which breaks down glycogen

Question 16

How does insulin work inside the cell to affect glycogen phosphorylase?

Same process with glycogen synthase

Answer 16

• Binds to surface receptor
• Activates tyrosine kinase
• TK phosphorylates an enzyme called protein phosphatase 1
• Protein phosphatase 1 (p) can then remove a phosphate group from GPKinase A, glycogen phosphorylase is then not active so you can then get glycogen breakdown

Question 17

How can glycogen phosphorylase be activated in the absence of hormones?

Answer 17

In muscles

• Calcium/calmodulin complex activated by muscles can directly activate GPKinase A, can then phosphorylate glycogen phosphorylase
• > Glycogen breakdown

Question 18

What is AMPs effect on Glucose and glycogen enzymes?

Answer 18

Activates Glycogen phosphorylase

-> Glucose

Question 19

What is the effect of ATP and Glucose on the glucose and glycogen enzymes?

Answer 19

Decreases the activity of glycogen phosphorylase

-> Glucose

Question 20

What is the effect of Glucose 6-P on the glucose and glycogen enzymes?

Answer 20

Activates/ increases activity of Glycogen synthase

- Glycogen

Question 21

What enzyme is defective in Von Gierke’s disease (1a)(Glycogen Storage Disease Type 1a)?

Answer 21

Glucose-6-phosphate deficiency (Type 1a)

Question 22

What is defective in Von Gierke’s disease (1b)(Glycogen Storage Disease Type 1b)?

Answer 22

Glucose transporter deficiency

Question 23

When and how does Von Gierke’s disease present?

Answer 23

Infancy (2-6 months of age)

• Severe hypoglycemia between meals (lethargy, seizures, lactic acidosis)
• Enlarged liver (excess glycogen) -> Liver failure

Question 24

What cycle becomes dysfunctional in those with Von Gierke’s disease?

Answer 24

Cori cycle (lactate cycle)

• G6P cannot be converted to glucose in liver
• Lactate builds up -> acidosis

Question 25

How is Von Gierke's disease diagnosed?

Answer 25

- DNA testing (preferred) | - Liver biopsy (historical test)

Question 26

How is Von Gierke's disease treated?

Answer 26

- Consumption of cornstarch between meals (glucose polymer) | - Avoidance of sucrose, lactose, fructose, galactose (worsen accumulation of G6P)

Question 27

What is the deficiency in Pompe's disease (glycogen storage disease type II)?

Answer 27

Acid alpha-glucosidase deficiency (also lysosomal acid maltase) - Accumulation of glycogen in lysosomes

Question 28

How does Pompe's disease (glycogen storage disease type II) present?

Answer 28

- Accumulation of glycogen in lysosomes - Classic form presents in infancy -> severe disease -> death in child/infant - Enlarged muscles - Cardiomegaly -> Death from HF - Enlarged tongue - Hypotonia - Hepatomegaly (from HF) - NO hypoglycemia / metabolic problems

Question 29

What is the deficiency in Cori's disease (glycogen storage disease type III)?

Answer 29

Debranching enzyme

Question 30

How does Cori's disease (glycogen storage disease type III) present?

Answer 30

- Hypoglycemia/hepatomegaly in child/infant (not as severe as Von Gierke) - No lactic acidosis (Cori's cycle intact) - Hypotonia/weakness - Muscle involvement (glycogen accumulation) (no - Gluconeogenesis intact - Possible cardiomyopathy w. hypertrophy

Question 31

What is the deficiency in McArdle's disease (glycogen storage disease type V)?

Answer 31

Muscle glycogen phosphorylase deficiency - Myophosphorylase deficiency - Skeletal muscle has unique isoform of G-phosphorylase - Glycogen not properly broken down in muscle cells

Question 32

How does McArdle's disease (glycogen storage disease type V) present?

Answer 32

Adolescence/ early childhood - Exercise intolerance, fatigue, cramps - Poor endurance, muscle swelling, and weakness - Myoglobinuria and C release (especially with exercise) - Urine may turn dark/red after exercise - Second wind in exercise - Flat venous lactate curve w. normal rise in ammonia levels during exercise

Question 33

What is the deficient enzyme in Andersen disease (type IV)?

Answer 33

Branching enzyme | - Neuromuscular form can present at any age

Question 34

How does Andersen disease (glycogen storage disease type IV) present?

Answer 34

- Hepatosplenomegaly and failure to thrive in early infancy - Infantile cirrhosis - Musscle weakness - Hypotonia - Cardiomyopathy -> early childhood death