Learning objectives for BIOCHEMISTRY

GLYCOGEN STRUCTURE & METABOLISM

CHAPTER 15
Be able to draw or describe the structure of glycogen with details
Understand what the key control step is in glycogen breakdown are and know the
details (including the substrate, enzyme and products) for the control point of this
process.
Understand the first 2 steps involved in glycogen synthesis are and know the details
(including the substrate, enzyme and products) for the control point of this process.
- Understand what glucagon, epinephrine and insulin in the blood stream means for
glycogen metabolism in both muscle and liver cells.

Sample problems for glycogen structure and metabolism

1. Glucose binds to and is a competitive inhibitor of glycogen phosphorylase, why does
this give the cell a physiological advantage?
2. How does the storage of glucose, as glycogen, prior to its use in glycolysis alter the
total amount of ATP that can be obtained from glucose through glycolysis, Krebs cycle
and oxidative phosphorylation? At what stage of glycogen metabolism does this energy
investment or release occur?
3. What is the advantage of glycogen breakdown by phosphorolysis rather than
hydrolysis?
a. the form of glucose that is released from glycogen is not easy to transport out of a cell
b. the form of glucose released from glycogen is ultimately the end result of the first step
in glycolysis
c. the form of glucose released from glycogen is in a high energy form and the
hydrolysis of ATP was not required for its formation
d. all of the above
e. a and b only

5. What are the two enzymes that are used to control glycogen metabolism?
6. Explain why the structure of glycogen is advantageous for its function?

7. What types of glycosidic bonds are glucose residues in the main chain of a glycogen
molecule making?

8. What types of glycosidic bonds are glucose residues at a branch point in a glycogen
molecule making?

9. How does the presence of the following molecules alter glycogen metabolism
9a. high levels of glucose-6-phosphate?
9b. high levels of ATP?
9c. glycogen synthase in a phosphorylated form?
9d. high levels of AMP?
9e. high levels of glucose?
9f. glycogen phosphorylase in a phosphorylated form?

11. Many diabetics do not respond to insulin because of a mutation in the insulin
receptor protein on their cells. How does this alter the rate of glycogen synthesis in
muscle?

12. Explain the effects of each of the following on the rates of gluconeogenesis and
glycogen metabolism:
12a. an increase in fructose-1,6-bisphosphate concentration
12b. high levels of glucose in the blood
12c. high concentration of insulin in the blood
12d. high levels of glucagon in the blood
12e. decreasing the levels of ATP, increasing levels of AMP
12f. decreasing the concentration of fructose-6-phosphate

13. When is insulin present in the bloodstream? What effect does insulin have on
glycogen metabolism?

Sample problems from Chapter 15 answer key

1. Glucose binds to and is a competitive inhibitor of glycogen phosphorylase, why does
this give the cell a physiological advantage?

This enzyme is the key step in breaking down glycogen into glucose, when the
cell has a high level of glucose there is no need to have more. So, by regulating glycogen
phosphorylase with respect to glucose concentrations the cell can conserve its glucose
reserves for time when glucose levels are low.
2. How does the storage of glucose, as glycogen, prior to its use in glycolysis alter the
total amount of ATP that can be obtained from glucose through glycolysis, Krebs cycle
and oxidative phosphorylation? At what stage of glycogen metabolism does this energy
investment or release occur?
The process of storing glucose as glycogen requires the use & hydrolysis of UTP (or
ATP), thus storing glucose first as glycogen causes a reduction in the amount of ATP that
the glucose molecule can produce by one ATP molecule. This assumes that glycolysis
starts with a glucose released from glycogen not glucose-6-phosphate (which is what we
normally release glucose as from glycogen).

3. What is the advantage of glycogen breakdown by phosphorolysis rather than

hydrolysis?
a. the form of glucose that is released from glycogen is not easy to transport out of a cell
b. the form of glucose released from glycogen is ultimately the end result of the first step
in glycolysis
c. the form of glucose released from glycogen is in a high energy form and the
hydrolysis of ATP was not required for its formation
d. all of the above
e. a and b only
ANSWER: e.

5. What are the two enzymes that are used to control glycogen metabolism?
Glycogen phosphorylase and glycogen synthase
6. Explain why the structure of glycogen is advantageous for its function?
The highly branched structure of glycogen allows the cell to store lots of glucose
in a molecule that has an overall compact spherical shape with lots of H-bonding
occurring between the individual sugar units. Thus, excess water is not needed to H-bond
with every sugar residue in the storage molecule.
7. What types of glycosidic bonds are glucose residues in the main chain of a glycogen
molecule making?
An (14) linkage, a glucose in the middle of the chain will be making two of
these and the glucose at the non-reducing end is only making one of these linkages
8. What types of glycosidic bonds are glucose residues at a branch point in a glycogen
molecule making?
This glucose is involved in 2 (14) linkages and one (16) linkage.

9. How does the presence of the following molecules alter glycogen metabolism
9a. high levels of glucose-6-phosphate? This molecule stimulates glycogen synthase
and increases glycogen formation. This also binds to glycogen phosphorylase in its T
state and slows glycogen breakdown.
9b. high levels of ATP? Binds to and inhibits glycogen phosphorylase and this inhibits
glycogen breakdown.
9c. glycogen synthase in a phosphorylated form? When phosphorylated this enzyme is
in the inactive form and so glycogen breakdown would be favored.
9d. high levels of AMP? This binds to and stabilizes glycogen phosphorylase in the Rstate, its more active form, this promotes glycogen breakdown.
9e. high levels of glucose? Bind to and inhibit glycogen phosphorylase, this inhibits
glycogen breakdown.
9f. glycogen phosphorylase in a phosphorylated form? This activates glycogen
phosphorylase and glycogen break down would be favored.

11. Many diabetics do not respond to insulin because of a mutation in the insulin
receptor protein on their cells. How does this alter the rate of glycogen synthesis in
muscle?
Insulin is unable to active glycogen synthesis.
12. Explain the effects of each of the following on the rates of gluconeogenesis and
glycogen metabolism:
12a. an increase in fructose-1,6-bisphosphate concentration
activates pyruvate kinase and increases glycolysis, inhibiting gluconeogenesis,
inhibits glycogen breakdown
12b. high levels of glucose in the blood
decreases gluconeogenesis and increases glycogen synthesis & glycolysis
12c. high concentration of insulin in the blood
inhibits gluconeogenesis & stimulates glycogen synthesis & glycolysis
12d. high levels of glucagon in the blood
inhibits glycogen synthesis & stimulates glycogen breakdown & gluconeogenesis
12e. decreasing the levels of ATP, increasing levels of AMP
stimulates glycolysis through both pyruvate kinase and phosphofructokinase,
gluconeogenesis is inhibited & increases glycogen breakdown
12f. decreasing the concentration of fructose-6-phosphate
this is not a regulatory molecule and would not alter glycolysis or
gluconeogenesis directly (if levels of glucose-6-phosphate fall then the then
gluconeogenesis is inhibited) but will stimulate glycogen synthesis through its ability to
be converted to and increase the cellular amount of glucose-6-phosphate.

NOTE: YOU ARE NOT RESPONSIBLE FOR THIS INFORMATION BUT IT IS

PROVIDED TO YOU AS FURTHE INFORMATION ABOUT HORMONAL
SIGNALLING:
Below are more details about the hormonal activation and resulting cellular
processes that change as a result of the hormone interacting with the receptor
protein on the cells surface.
What is the effect in liver cells (hepatocytes) of glucagon in the bloodstream?
Glucagon binds its receptor protein (which is only on liver cells) to signal low
blood glucose levels the goal is to stimulate glucose production in these cells and secret
this glucose into the blood stream.
This sets off an enzyme cascade pathway which increases the cellular amounts of cAMP
(a secondary messenger).
This activates PKA (protein kinase A) which phosphorylates:
1. And activates glycogen phosphorylase thereby increasing glycogen
breakdown.
2. And activates fructose-1,6-bisphosphatase-2 which decreases the amount of F2,6-BP which leads to an activation of FBPase and gluconeogenesis. This also results in
a decrease in Phosphofructokinase-1 activity causing a decrease in glycolysis.
3. And inactivates glycogen synthase thereby decreasing glycogen synthesis
NOTE: the effects of epinephrine on liver cells is the same.
What is the effect in muscle cells of epinephrine in the bloodstream?
Epinephrine binds its receptor protein to signal low blood glucose levels
This sets off an enzyme cascade pathway, which increases the cellular amounts of camp
& Ca2+ (secondary messengers).
This activates PKA (protein kinase A) which phosphorylates:
1. And activates glycogen phosphorylase thereby increasing glycogen
breakdown.
2. and activates Phosphofructokinase-2 which increases the amount of F-2,6-BP
which leads to an activation of glycolysis.
3. And inactivates glycogen synthase thereby decreasing glycogen synthesis
Note: these cells cannot do gluconeogenesis.
What effect does insulin have on muscle and liver cells?
Insulin binds its receptor protein to signal high blood glucose levels, this
stimulates cells to transport glucose into the cell (increasing the cellular amount of
glucose) this increases glycolysis (decreases gluconegenesis in liver cells) and glycogen
synthesis.
This sets off an enzyme cascade pathway, the MAP kinase pathway.
This activates PP1 (phosphoprotein phosphatase) which dephosphorylates:
1. And inactivates glycogen phosphorylase thereby decreasing glycogen
breakdown.
2. And activates glycogen synthase thereby increasing glycogen synthesis
Also, genes that are needed for glucose breakdown and expressed (more of the proteins
needed are made).