BIOC 202 Problem Set 9

Glycogen Metabolism
Lehninger, 7th Edition, Chapter 15: Pgs 615-618: 3, 5, 6, 10

3. Effect of O2 Supply on Glycolytic Rates The regulated steps of glycolysis in intact cells
can be identified by studying the catabolism of glucose in whole tissues or organs. For
example, the glucose consumption by heart muscle can be measured by artificially
circulating blood through an isolated intact heart and measuring the concentration of
glucose before and after the blood passes through the heart. If the circulating blood is
deoxygenated, heart muscle consumes glucose at a steady rate. When oxygen is added
to the blood, the rate of glucose consumption drops dramatically, then is maintained at
the new, lower rate. Explain.

5. Cellular Glucose Concentration The concentration of glucose in human blood plasma is

maintained at about 5 mM. The concentration of free glucose inside a myocyte is much
lower. Why is the concentration so low in the cell? What happens to glucose after entry
into the cell? Glucose is administered intravenously as a food source in certain clinical
situations. Given that the transformation of glucose to glucose 6-phosphate consumes
ATP, why not administer intravenous glucose 6- phosphate instead?
6. Enzyme Activity and Physiological Function The Vmax of the glycogen phosphorylase
from skeletal muscle is much greater than the Vmax of the same enzyme from liver
tissue.
a. What is the physiological function of glycogen phosphorylase in skeletal muscle?
In liver tissue?
b. Why does the Vmax of the muscle enzyme need to be greater than that of the
liver enzyme?

10. Glycogen Breakdown in Migrating Birds Unlike the rabbit with its short dash, migratory
birds require energy for extended periods of time. For example, ducks generally fly
several thousand miles during their annual migration. The flight muscles of migratory
birds have a high oxidative capacity and obtain the necessary ATP through the oxidation
of acetyl-CoA (obtained from fats) via the citric acid cycle. Compare the regulation of
muscle glycolysis during short-term intense activity, as in the fleeing rabbit, and during
extended activity, as in the migrating duck. Why must the regulation in these two
settings be different?
 BIOC 202 Problem Set 9
Glycogen Metabolism
Stryer, 9th Edition, Chapter 21: Pgs 704-707: 1-6, 7(a-e only), 8-10., 13, 16, 18, 26(a-f only), 27, 28, 31, 32, 38
1. Step-by-step degradation. What are the three steps in glycogen degradation and what
enzymes are required?

2. Product Identification.The immediate product Of glycogen phosphorylase is:

a. Glucose 6-phosphate.
b. Glucose 1-phosphate.
c. Fructose 1-phosphate.
d. Glucose 1,6-bisphosphate.

3. Reaction type. Glycogen phosphorylase degrades glycogen by:

a. A Hydrolysis Reaction.
b. An Oxidation-reduction reaction.
c. A Phosphorolysis Reaction.
d. A Transferase Reaction.

4. Teamwork. Which of the following enzymes are not directly involved in glycogen
degradation?
a. Phosphoglucose Isomerase
b. α-1,6-Glucosidase
c. Glycogen Phosphorylase
d. Transferase

5. Activated Glucose. Which of the following is substrate for glycogen synthase?

a. UTP-glucose
b. Glucose1-phosphate
c. CDP-glucose
d. UDP-glucose
6. Inappropriate. Which of the following enzymes is not required for glycogen synthesis?
a. Glycogenin
b. Branching enzyme
 c. Glycogen Synthase
d. α-1,6-Glucosidase

7. Match’em. Match each term with its description. (a-e only)

8. Choice is good. Glycogen is not as reduced as fatty acids are and consequently not as
energy rich. Why do animals store any energy as glycogen? Why not convert all excess
fuel into fatty acids?
9. If a little is good,alot is better. α-Amylose is an unbranched glucose polymer. Why would
this polymer not be as effective a storage form of glucose as glycogen?

10. Speed matters.Liver and skeletal muscle have different isozymic forms of glycogen
phosphorylase that differ in a number of ways as discussed in the text. One notable
difference is that the Vmax of muscle phosphorylase is considerably greater than the
Vmax of liver phosphorylase. Explain why this difference makes good physiological
sense.

13. Excessive storage. Suggest an explanation for the fact that the amount of glycogen in
type I glycogen-storage disease (von Gierke disease) is increased. Note: For question 13,
people with von Gierke disease (type I glycogen storage disorder) fail to make functional
glucose-6-phosphatase in the liver

16. Hydrophobia. Why is water excluded from the active site of phosphorylase? Predict the
effect of a mutation that allows water molecules to enter.
18. Two in one. A single polypeptide chain houses the transferase and debranching
enzymes. Cite a potential advantage of this arrangement.

26. Yin and Yang. Match the terms on the left with the descriptions on the right.
a. UDP-glucose Has glucose1-phosphateas one of its substrates

b. UDP-glucosepyrophosph Potent activator of glycogen synthase b

orylase

c. Glycogensynthase Glucosesensorintheliver

d. Glycogenin Activated substrate for glycogen synthesis

e. Branchingenzyme Synthesizes α-1,4 linkages between glucose

molecules

f. Glucose 6-phosphate Leads to the inactivation of glycogen synthase

kinase

g. Glycogensynthasekinase Synthesizes α-1,6 linkages between glucose

molecules

h. Proteinphosphatase1 Catalyzes the formationof glycogen synthase b

i. Insulin Catalyzestheformationof glycogen synthase a

j. Glycogenphosphorylasea Providestheprimerfor glycogen synthesis

27. Team effort. What enzymes are required for the synthesis of a glycogen particle starting
from glucose 6-phosphate?
28. Force it forward. The following reaction accounts for the synthesis of UDP-glucose. This
reaction is readily reversible. How is it made irreversible in vivo?
Glucose 1-phosphate+UTP⇌UDP-glucose+PPi

31. Dual roles. Phosphoglucomutase is crucial for glycogen breakdown as well as for
glycogen synthesis. Explain the role of this enzyme in each of the two processes.

32. Working at cross-purposes. Write a balanced equation showing the effect of

simultaneous activation of glycogen phosphorylase and glycogen synthase. Include the
reactions catalyzed by phosphoglucomutase and UDP-glucose pyrophosphorylase.
38. Working together. What enzymes are required for the liver to release glucose into the
blood when an organism is asleep and fasting?
 BIOC 202 Problem Set 9
Gluconeogenesis
Lehninger, 7th Edition, Chapter 14: Pgs 570-574: 17, 19-23, 24a,b,c,&d, 27, 28

17. Synthesis of Glycerol Phosphate The glycerol 3-phosphate required for the synthesis of
glycerophospholipids can be synthesized from a glycolytic intermediate. Propose a
reaction sequence for this conversion.

19. Muscle Wasting in Starvation One consequence of starvation is a reduction in muscle

mass. What happens to the muscle proteins?

20. Pathway of Atoms in Gluconeogenesis A liver extract capable of carrying out all the
normal metabolic reactions of the liver is briefly incubated in separate experiments with

the following 14C-labeled precursors.

Trace the pathway of each precursor through gluconeogenesis. Indicate the location of 14C in all
intermediates and in the product, glucose.
21. Energy Cost of a Cycle of Glycolysis and Gluconeogenesis What is the cost (in ATP
equivalents) of transforming glucose to pyruvate via glycolysis and back again to glucose
via gluconeogenesis?

22. Relationship between Gluconeogenesis and Glycolysis Why is it important that

gluconeogenesis is not the exact reversal of glycolysis?

23. Energetics of the Pyruvate Kinase Reaction Explain in bioenergetic terms how the
conversion of pyruvate to phosphoenolpyruvate in gluconeogenesis overcomes the
large, negative, standard free-energy change of the pyruvate kinase reaction in
glycolysis.
 24. Glucogenic Substrates A common procedure for determining the effectiveness of
compounds as precursors of glucose in mammals is to starve the animal until the liver
glycogen stores are depleted and then administer the compound in question. A
substrate that leads to a net increase in liver glycogen is termed glucogenic, because it
must first be converted to glucose 6-phosphate. Show by means of known enzymatic
reactions which of the following substances are glucogenic.

d
27. Relationship between Fructose 1,6-Bisphosphatase and Blood Lactate Levels A
congenital defect in the liver enzyme fructose 1,6- bisphosphatase results in abnormally
high levels of lactate in the blood plasma. Explain.

28. Effect of Phloridzin on Carbohydrate Metabolism Phloridzin, a toxic glycoside from the
bark of the pear tree, blocks the normal reabsorption of glucose from the kidney tubule,
thus causing blood glucose to be almost completely excreted in the urine. In an
experiment, rats fed phloridzin and sodium succinate excreted about 0.5 mol of glucose
(made by gluconeogenesis) for every 1 mol of sodium succinate ingested. How is the
succinate transformed to glucose? Explain the stoichiometry.
 BIOC 202 Problem Set 9
Gluconeogenesis
Stryer, 9th Edition, Chapter 16: Pg. 535-540: 22(all but i), 23(a-f, &j only), 34, 35(1-5 only), 36-42, 44(all but c), 45, 47, 50, 61
22. Match’em 1. The following sequence is a part of the sequence of reactions in
gluconeogenesis.
Pyruvate → A Oxaloacetate → B Malate → C Oxaloacetate → D Phosphoenolpyruvate
takes place in mitochondria

takes place in the cytoplasm

Produces CO2

Consumes CO2

Requires NADH

Produces NADH

Requires ATP

Requires GTP

requires biotin

Is regulated by acetylCoA
23. (a-f, &j only)
34. It is not hard to meet expenses. They are everywhere. What energetic barrier prevents
glycolysis from simply running in reverse to synthesis glucose? What is the energetic cost
to overcome this barrier?

35. Match'em 2.Indicate Which Of The Conditions Listed In The Right-hand column increase
the activity of the glycolytic and gluconeogenic pathways.

36. Waste not, want not. Why is the conversion of lactic acid from the blood into glucose in
the liver in an organism’s best interest?

37. Road blocks bypassed. How are the irreversible reactions of glycolysis bypassed in
gluconeogenesis?
38. Pointlessness Averted. What are the regulatory means that Prevent high levels of activity
in glycolysis and gluconeogenesis simultaneously?

39. Different needs. Liver is primarily a gluconeogenic tissue,whereas muscle is primarily

glycolytic. Why does this division of labor make good physiological sense?

40. Never let me go. Why does the lack of glucose 6-phosphatase activity in the brain and
muscle make good physiological sense?

41. Counting high-energy compounds 1.How many NTP molecules are required for the
synthesis of one molecule of glucose from two molecules of pyruvate? How many NADH
molecules?

42. Counting high-energy compounds 2.How many NTP molecules are required to synthesize
glucose from each of the following compounds?
a. Glucose6-phosphate
b. Fructose 1,6-bisphosphate
c. Two Molecules Of Oxaloacetate
 d. Two Molecules Of Dihydroxyacetone Phosphate
a

44. Metabolic mutants. Predict the effect of each of the following mutations on the pace of
glycolysis in liver cells:
a. Loss of the allosteric site for ATP in phosphofructokinase
b. Loss of the binding site for citrate on phosphofructokinase
c. Loss of the phosphatase domain of bifunctional enzyme that controls the level of
fructose 2,6-bisphosphate
d. Loss Of The Binding Site For Fructose 1,6-bisphosphate pyruvate kinase

45. Yet another metabolic mutant. What are the likely consequences of genetic disorder
rendering fructose 1,6-bisphosphatase in the liver less sensitive to regulation by fructose
2,6-bisphosphate?
47. Tracing carbon atoms 2. If cells synthesizing glucose from lactate are exposed to CO2
labeled with 14C, what will be the distribution of label in the newly synthesized glucose?

50. Working At Cross-purposes?Gluconeogenesis Takes Place During intense exercise, which

seems counterintuitive. Why would an organism synthesize glucose and at the same
time use glucose to generate energy?

61. If glucose is such a readily available fuel, why is gluconeogenesis necessary?