L20- Glycogen Metabolism

Question 1

Describe the structure of glycogen.

Answer 1

Glycogen is composed of glucose molecules linked linearly with alpha(1->4) bonds, with branching chains linked alpha(1->6) to the main glucose chain at intervals of approximately eight residues.

Question 2

In which tissue(s) is glycogen primarily synthesized and stored?

Answer 2

Liver and muscle.

Question 3

Most of the liver glycogen stores are depleted after how many hours of fasting?

Answer 3

12-18 hours.

Question 4

For what purpose does the liver break down glycogen?

Answer 4

To maintain blood glucose levels, especially during an episode of fasting.

Question 5

For what purpose does muscle break down glycogen?

Answer 5

To make ATP for muscle contractions.

Question 6

What is the reaction carried out by glycogen synthase?

Answer 6

Glycogen synthase attaches the C1 of an activated UDP-glucose to the C4-OH of a terminal glucose on a pre-existing glycogen chain (leads to the formation of a linear polymer of glucose residues).

Question 7

What protein acts as a primer for glycogen synthesis?

Answer 7

Glycogenin.

Question 8

Describe the mechanism by which glycogen branching enzyme synthesizes glycogen branches.

Answer 8

Glycogen branching enzyme cleaves off a glycogen fragment of seven glucose units from the terminal end of a linear glycogen chain that is 12-16 units long. The enzyme then re-attaches the fragment through an alpha(1->6) bond to a glucose at least four residues beyond the last branch.

Question 9

Under what physiologic condition does the liver synthesize glycogen?

Answer 9

Glycogenesis occurs in the liver when blood sugar levels rise above resting levels.

Question 10

Name the enzyme(s) that carry out glycogen breakdown.

Answer 10

Glycogen phosphorylase and debranching enzyme.

Question 11

Name the enzyme(s) that carry out glycogen synthesis.

Answer 11

Glycogen synthase and branching enzyme.

Question 12

Which enzyme cleaves glucose residues one at a time from the end of an alpha(1->4) linked glycogen chain?

Answer 12

Glycogen phosphorylase.

Question 13

What kind of enzymatic reaction does glycogen phosphorylase catalyze?

Answer 13

Phosphorolysis.

Question 14

What is the product of the phosphorolytic cleavage of glucose residues by glycogen phosphorylase?

Answer 14

Glucose-1-phosphate.

Question 15

What are the two activities of debranching enzyme?

Answer 15

Glucan transferase activity and alpha(1->6) glucosidase activity.

Question 16

What is the reaction carried out by the glucan transferase activity of debranching enzyme?

Answer 16

The glucan transferase activity cleaves a trisaccharide fragment from the end of a 4-residue-long branched chain, and re-attaches that fragment through an alpha(1->4) linkage to the end of a different chain.

Question 17

What remains attached at the glycogen branch point after action of the glucan transferase activity of debranching enzyme?

Answer 17

A single glucose residue attached to a chain via an alpha(1->6) linkage.

Question 18

Which enzyme catalyzes the cleavage of alpha(1->6) linkages at glycogen branch points?

Answer 18

The alpha(1->6) glucosidase activity of debranching enzyme.

Question 19

What kind of enzymatic reaction does the alpha(1->6) glucosidase activity of debranching enzyme catalyze?

Answer 19

Hydrolysis.

Question 20

What molecule is released from the hydrolytic cleavage of alpha(1->6) linkages by the glucosidase activity of debranching enzyme?

Answer 20

Free glucose.

Question 21

What enzyme catalyzes the conversion of glucose-6-phosphate to free glucose?

Answer 21

Glucose-6-phosphatase.

Question 22

What is the major product of glycogenolysis?

Answer 22

Glucose-1-phosphate.

Question 23

Glycogen metabolism in muscle responds to which hormone(s)?

Answer 23

Epinephrine and insulin (but not glucagon).

Question 24

Glycogen metabolism in the liver responds to which hormone(s)?

Answer 24

Epinephrine, insulin and glucagon.

Question 25

True or False. Glycogen phosphorylase is more active when it is not phosphorylated, whereas glycogen synthase is more active when it is phosphorylated.

Answer 25

False. It is the opposite: glycogen phosphorylase is more active when it is phosphorylated, whereas glycogen synthase is more active when it is not phosphorylated.

Question 26

The binding of glucagon and epinephrine to specific cell surface receptors leads to the cAMP-dependent activation of which enzyme involved in the regulation of glycogen metabolism?

Answer 26

Protein kinase A (also called cAMP-dependent protein kinase).

Question 27

What is the effect of glucagon on the activity of glycogen synthase and glycogen phosphorylase?

Answer 27

Glucagon decreases the activity of glycogen synthase and increases the activity of glycogen phosphorylase.

Question 28

What is the effect of insulin on the activity of glycogen synthase and glycogen phosphorylase?

Answer 28

Insulin increases the activity of glycogen synthase and decreases the activity of glycogen phosphorylase.

Question 29

What is the effect of elevated glucose and fructose-1-phosphate on glycogen synthase and glycogen phosphorylase?

Answer 29

Glucose and fructose-1-phosphate decrease glycogen breakdown by favoring the inactivation of glycogen phosphorylase and the activation of glycogen synthase.

Question 30

What is the effect of elevated glucose-6-phosphate on glycogen metabolism?

Answer 30

Glucose-6-phosphate stimulates glycogen synthesis.

Question 31

How does glucose-6-phosphate stimulate glycogen synthesis?

Answer 31

Glucose-6-phosphate inhibits the protein kinase that phosphorylates glycogen synthase. This maintains glycogen synthase in its active form, favoring glycogen synthesis.

Question 32

How does glycogen limit its own synthesis?

Answer 32

Glycogen accumulation inhibits protein phosphatase. This prevents glycogen synthase from being activated while maintaining glycogen phosphorylase in its active form.

Question 33

Phosphorylase kinase is activated by calcium. How does this work?

Answer 33

The protein calmodulin binds calcium. Calcium-bound calmodulin then activates the kinase that phosphorylates phosphorylase kinase, thus activating it.

Question 34

Which glycogen storage disease is characterized by the accumulation of glycogen within lysosomes, particularly in muscle cells?

Answer 34

Type II (Lysosomal acid maltase deficiency, also referred to as Pompe).

Question 35

Debranching enzyme deficiency results in which glycogen storage disease?

Answer 35

Type III (also referred to as Forbes-Cori).

Question 36

Which glycogen storage disease is characterized by deposits of abnormal glycogen in the liver, leading to progressive liver cirrhosis and death by the second year?

Answer 36

Type IV (Branching enzyme deficiency, also referred to as Anderson).

Question 37

Which glycogen storage disease is characterized by muscle cramps during vigorous exercise, lack of lactate after vigorous exercise, and higher amounts of normal-structured glycogen?

Answer 37

Type V (muscle phosphorylase deficiency, also referred to as McArdle).

Question 38

Which glycogen storage disease is characterized by muscle cramping and exercise intolerance? It is also sometimes associated with hemolytic anemias.

Answer 38

Type VII (muscle phosphofructokinase deficiency, also referred to as Tarui).

Question 39

Which glycogen storage disease is characterized by hypoglycemia between meals, hyperlipidemia, acidosis, and poor growth?

Answer 39

Type I (Glucose-6-phosphatase deficiency).