Chapter 21, Glycogen Metabolism Video Solutions, Biochemistry

04:58

Problem 1

What are the three steps in glycogen degradation and what enzymes are required?

Jessica Honkomp

Numerade Educator

02:39

Match each term with its description.
(a) Glycogen phosphorylase _____
(b) Phosphorolysis ______
(c) Transferase _____
(d) $\alpha-1,6-$ Glucosidase ______
(e) Phosphoglucomutase ______
(f) Phosphorylase kinase ______
(g) Protein kinase $A$ ______
(h) Calmodulin ______
(i) Epinephrine _______
(j) Glucagon ______
1. Calcium-binding subunit of phosphorylase kinase
2. Activates glycogen phosphorylase
3. Removal of a glucose residue by the addition of phosphate
4. Stimulates glycogen breakdown in muscle
5. Liberates a free glucose residue
6. Shifts the location of several glucose residues
7. Stimulates glycogen breakdown in the liver
8. Catalyzes phosphorolytic cleavage
$9 .$ Prepares glucose 1 -phosphate for glycolysis
10. Phosphorylates phosphorylase kinase

Jessica Honkomp

Numerade Educator

06:47

Problem 3

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?

Danielle Ashley

Numerade Educator

01:16

Problem 4

$\alpha$ -Amylose is an unbranched glucose polymer. Why would this polymer not be as effective a storage form of glucose as glycogen?

Prashant Bana

Numerade Educator

08:44

Problem 5

A sample of glycogen from a patient with liver disease is incubated with orthophosphate, phosphorylase, the transferase, and the debranching enzyme $(\alpha-1,6-\text { glucosidase }) .$ The ratio of glucose 1 -phosphate to glucose formed in this mixture is $100 .$ What is the most likely enzymatic deficiency in this patient?

Danielle Ashley

Numerade Educator

06:08

Problem 6

Compare the allosteric regulation of phosphorylase in the liver and in muscle, and explain the significance of the difference.

Danielle Ashley

Numerade Educator

04:04

Problem 7

The reaction catalyzed by phosphorylase is readily reversible in vitro. At $\mathrm{pH} 6.8,$ the equilibrium ratio of orthophosphate to glucose 1 -phosphate is 3.6. The value of $\Delta G^{\circ}$ 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.

Danielle Ashley

Numerade Educator

04:27

Problem 8

Suggest an explanation for the fact that the amount of glycogen in type I glycogen-storage disease (von Gierke disease) is increased.

Danielle Ashley

Numerade Educator

06:32

Problem 9

The phosphoryl group on phosphoglucomutase is slowly lost by hydrolysis. Propose a mechanism that utilizes a known catalytic intermediate for restoring this essential phosphoryl group. How might this phosphoryl donor be formed?

Danielle Ashley

Numerade Educator

04:11

Problem 10

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. Account for the different manifestations of the absence of glycogen phosphorylase in the two tissues. What does the existence of these two different diseases indicate about the genetic nature of the phosphorylase?

Danielle Ashley

Numerade Educator

05:18

Problem 11

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

Danielle Ashley

Numerade Educator

04:04

Problem 12

In human liver extracts, the catalytic activity of glycogenin was detectable only after treatment with $\alpha$ -amylase, an enzyme the hydrolyzes $\alpha-1,4$ -bonds in starch and glycogen. Why was $\alpha$ -amylase necessary to reveal the glycogenin activity?

Danielle Ashley

Numerade Educator

05:09

Problem 13

A single polypeptide chain houses the transferase and debranching enzyme. Cite a potential advantage of this arrangement.

Danielle Ashley

Numerade Educator

01:06

Problem 14

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.

Prashant Bana

Numerade Educator

02:47

Problem 15

What is the rationale for the inhibition of muscle glycogen phosphorylase by glucose 6 -phosphate when glucose 1 -phosphate is the product of the phosphorylase reaction?

Danielle Ashley

Numerade Educator

02:37

Problem 16

Outline the signaltransduction cascade for glycogen degradation in muscle.

Vishal Sharma

Numerade Educator

04:07

Problem 17

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?

Danielle Ashley

Numerade Educator

03:44

Problem 18

Phosphorylation has opposite effects on glycogen synthesis and breakdown. What is the advantage of its having opposing effects?

Danielle Ashley

Numerade Educator

06:09

Problem 19

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.

Danielle Ashley

Numerade Educator

00:26

Problem 20

What accounts for the fact that liver phosphorylase is a glucose sensor, whereas muscle phosphorylase is not?

Carlene Jimenez

Numerade Educator

04:11

Problem 21

Match the terms on the left with the descriptions on the right.
(a) UDP-glucose ______
(b) UDP-glucose pyrophosphorylase _______
(c) Glycogen synthase ______
(d) Glycogenin ______
(e) Branching enzyme ______
(f) Glucose 6 -phosphate ______
(g) Glycogen synthase kinase(h) Protein phosphatase 1 ______
(i) Insulin ______
(j) Glycogen phosphorylase $a$ _______
1. Glucose $1-$ phosphate is one of its substrates.
2. Potent activator of glycogen synthase $b$
3. Glucose sensor in the liver.
4. Activated substrate for glycogen synthesis.
5. Synthesizes $\alpha-1,4$ linkages between glucose molecules.
6. Leads to the inactivation of glycogen synthase kinase.
7. Synthesizes $\alpha-1,6$ linkages between glucose molecules.
8. Catalyzes the formation
of glycogen synthase $b$
9. Catalyzes the formation
of glycogen synthase $a$
10. Provides the primer for glycogen synthesis.

Danielle Ashley

Numerade Educator

06:56

Problem 22

What enzymes are required for the synthesis of a glycogen particle starting from glucose 6 -phosphate?

Danielle Ashley

Numerade Educator

04:32

Problem 23

The following reaction accounts for the synthesis of UDP-glucose. This reaction is readily reversible. How is it made irreversible in vivo? (EQUATION CANNOT COPY)

Danielle Ashley

Numerade Educator

01:20

Problem 24

Why does activation of the phosphorylated $b$ form of glycogen synthase by high concentrations of glucose 6 -phosphate make good biochemical sense?

Hailey Tomashek

Numerade Educator

01:57

Problem 25

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

Subash Charan

Numerade Educator

00:36

Problem 26

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

Eleanor Behling

Numerade Educator

02:50

Problem 27

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.

Danielle Ashley

Numerade Educator

03:21

Problem 28

Glycogen synthase requires a primer. A primer was formerly thought to be provided when the existing glycogen granules are divided between the daughter cells produced by cell division. In other words, parts of the original glycogen molecule were simply passed from generation to generation. Would this strategy have been successful in passing glycogen stores from generation to generation? How are new glycogen molecules now known to be synthesized?

Danielle Ashley

Numerade Educator

03:11

Problem 29

How does insulin stimulate glycogen synthesis?

Danielle Ashley

Numerade Educator

Problem 30

Enzymes of the $\alpha$ -amylase family (problem 12 ) catalyze a reaction by forming a covalent intermediate to a conserved aspartate residue. Propose mechanisms for the two enzymes catalyzing steps in glycogen debranching on the basis of their potential membership in the $\alpha$ -amylase family.

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00:27

Problem 31

What pathway in addition to the cAMP-induced signal transduction pathway is used in the liver to maximize glycogen breakdown?

Sam Limsuwannarot

Numerade Educator

03:51

Problem 32

Write a balanced equation for the formation of glycogen from galactose.

Danielle Ashley

Numerade Educator

03:56

Problem 33

What enzymes are required for the liver to release glucose into the blood when an organism is asleep and fasting?

Danielle Ashley

Numerade Educator

02:47

Problem 34

Crystals of phosphorylase $a$ grown in the presence of glucose shatter when a substrate such as glucose 1-phosphate is added. Why?

Danielle Ashley

Numerade Educator

01:46

Problem 35

UDP-glucose is the activated form of glucose used in glycogen synthesis. However, we have previously met other similar activated forms of carbohydrate in our consideration of metabolism. Where else have we seen UDP-carbohydrate?

Shahina -

Numerade Educator

01:52

Problem 36

Suggest another mutation in glucose metabolism that causes symptoms similar to those of von Gierke disease.

Jennifer Stoner

Numerade Educator

06:56

Problem 37

Experiments were performed in which serine (S) 14 of glycogen phosphorylase was replaced by glutamate $(\mathrm{E}) .$ The $\mathrm{V}_{\max }$ of the mutant enzyme was then compared with the wild type phosphorylase in both the $a$ and the $b$ form. (TABLE CANNOT COPY)
(a) Explain the results obtained with the mutant.
(b) Predict the effect of substituting aspartic acid for the serine.

Shazia Naz

Numerade Educator

04:04

Problem 38

The liver is a major storage site for glycogen. Purified from two samples of human liver, glycogen was either treated or not treated with $\alpha$ -amylase and subsequently analyzed by SDS-PAGE and western blotting with the use of antibodies to glycogenin. The results are presented in the adjoining illustration on the next page. (a) Why are no proteins visible in the lanes without amylase treatment?
(b) What is the effect of treating the samples with $\alpha$ -amylase? Explain the results.
(c) List other proteins that you might expect to be associated with glycogen. Why are other proteins not visible?

Danielle Ashley

Numerade Educator

04:39

Problem 39

The gene for glycogenin was transfected into a cell line that normally stores only small amounts of glycogen. The cells were then manipulated according to the following protocol, and glycogen was isolated and analyzed by SDS-PAGE and western blotting by using an antibody to glycogenin with and without $\alpha$ -amylase treatment. The results are presented in the adjoining illustration. (FIGURE CANNOT COPY)
The protocol: Cells cultured in growth medium and
$25 \mathrm{mM} \text { glucose (lane } 1)$ were switched to medium containing no glucose for 24 hours (lane 2 ). Glucose-starved cells were refed with medium containing $25 \mathrm{mM}$ glucose for 1 hour (lane 3 ) or 3 hours (lane 4 ). Samples $(12$ \mug of protein) were either treated or not treated with $\alpha$ -amylase, as indicated, before being loaded on the gel.
(a) Why did the western analysis produce a "smear" - that is, the high-molecular-weight staining in lane $1(-) ?$
(b) What is the significance of the decrease in highmolecular-weight staining in lane $2(-) ?$
(c) What is the significance of the difference between lanes $2(-)$ and $3(-) ?$
(d) Suggest a plausible reason why there is essentially no difference between lanes $3(-)$ and $4(-)$
(e) Why are the bands at $66 \mathrm{kDa}$ the same in the lanes treated with amylase, despite the fact that the cells were treated differently?

Nathan Silvano

Numerade Educator