1.  Step-by-step degradation. What are the three steps in glycogen degradation, and what enzymes catalyze each step? ✓ 1

2.  Tweedledum and Tweedledee. Match each term with its description. ✓ 1

3.  For the greater good. Why is the control of glycogen different in muscle and the liver? ✓ 2

4.  Get out of the way! What structural difference accounts for the fact that the T state of phosphorylase kinase is less active than the R state? ✓ 2

5.  The regulator’s regulator. What factors result in maximal activation of phosphorylase kinase? ✓ 2

6.  Not all absences are equal. Hers disease results from an absence of liver glycogen phosphorylase and may result in serious illness. In McArdle disease, muscle glycogen phosphorylase is absent. Although exercise is difficult for patients suffering from McArdle disease, the disease is rarely life threatening. ✓ 2

(a) Account for the different manifestations of the absence of glycogen phosphorylase in the two tissues.

(b) What does the existence of these two different diseases indicate about the genetic nature of the phosphorylase?

7.  Dare to be different. Compare the allosteric regulation of phosphorylase in the liver and in muscle, and explain the significance of the difference. ✓ 2

8.  An appropriate inhibitor. What is the biochemical rationale for the inhibition of muscle glycogen phosphorylase by glucose 6-phosphate when glucose 1-phosphate is the product of the phosphorylase reaction? ✓ 2

9.  Metamorphoses. What is the predominant form of glycogen phosphorylase in resting muscle? Immediately after exercise begins, this form is activated. How does this activation take place? ✓ 2

10.  Passing along the information. Outline the signal-transduction cascade for glycogen degradation in muscle. ✓ 2

11.  Double activation. What path in addition to the cAMP-induced signal transduction is used in the liver to maximize glycogen breakdown? ✓ 2

12.  Slammin’ on the brakes. There must be a way to shut down glycogen breakdown quickly to prevent the wasteful depletion of glycogen after energy needs have been met. What mechanisms are employed to turn off glycogen breakdown? ✓ 2

13.  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?

14.  Feeling depleted. Glycogen depletion resulting from intense, extensive exercise can lead to exhaustion and the inability to continue exercising. Some people also experience dizziness, an inability to concentrate, and a loss of muscle control. Account for these symptoms.

15.  Family resemblance. In problem 23 of Chapter 16, you were asked to consider the effects of exposing glycolytically active cells to arsenate. Recall that arsenate can substitute for phosphate, but that arsenate esters are unstable and spontaneously decompose to arsenate and a carboxylic acid. What will the energetic consequences be if glycogen phosphorylase uses arsenate instead of phosphate? ✓ 1

16.  Working together. One of the liver’s key roles is the maintenance of blood-glucose concentration when an organism is fasting, such as during a night’s sleep. Mobilizing liver glycogen requires enzymatic teamwork. Identify the enzymes that are required for the liver to release glucose into the blood. ✓ 1

17.  Everyone has a job to do. What accounts for the fact that liver phosphorylase is a glucose sensor, whereas muscle phosphorylase is not? ✓ 2

18.  If a little is good, a lot is better. Amylose is an unbranched glucose polymer. Why would this polymer not be as effective a storage form of glucose as glycogen?

20.  Two in one. A single polypeptide chain houses the transferase and debranching enzyme. What is a potential advantage of this arrangement? ✓ 2

21.  How did they do that? A strain of mice has been developed that lack the enzyme phosphorylase kinase. Yet, after strenuous exercise, the glycogen stores of a mouse of this strain are depleted. Explain how this depletion is possible. ✓ 2

22.  A shattering experience. Crystals of phosphorylase a grown in the presence of glucose shatter when a substrate such as glucose 1-phosphate is added. Why? ✓ 2

23.  Two for the binding of one. Glycogen breakdown in the liver is stimulated by glucagon. What other carbohydrate-metabolism pathway in the liver is stimulated by glucagon?

24.  An ATP saved is an ATP earned. The complete oxidation of glucose 6-phosphate derived from free glucose yields 30 molecules of ATP, whereas the complete oxidation of glucose 6-phosphate derived from glycogen yields 31 molecules of ATP. Account for this difference. ✓ 1

25.  A thumb on the balance. The reaction catalyzed by phosphorylase is readily reversible in vitro. At pH 6.8, the equilibrium ratio of orthophosphate to glucose 1-phosphate is 3.6. The value of ΔG°′ for this reaction is small because a glycosidic bond is replaced by a phosphoryl ester bond that has a nearly equal transfer potential. However, phosphorolysis proceeds far in the direction of glycogen breakdown in vivo. Suggest one means by which the reaction can be made irreversible in vivo. ✓ 1

26.  Hydrophobia. Why is water excluded from the active site of phosphorylase? Predict the effect of a mutation that allows water molecules to enter.

27.  Quenching release. Type 2 diabetes is a condition characterized by insulin resistance and high blood-glucose concentration. Research is underway to develop inhibitors of glycogen phosphorylase as a possible treatment for type 2 diabetes. What is the rationale for this strategy, and what is one potential problem with the approach?