Deck 14: Carbohydrates: Glycogen Metabolism

Question 1

You are examining the biochemical characteristics of the liver dysfunction in your patient who is exhibiting signs of a GSD. You have isolated the microsomal fraction (contains the endoplasmic reticulum) of a liver biopsy homogenate from your patient and a control individual for your studies. Incubation with radioactive phosphate-labeled glucose 6-phosphate results in an increase in isotope associated with the microsomes from your control sample but no increase in association with the microsomes from your patient. These results are best explained by a defect in which of the following?

A) glucose-6-phosphatase activity in the microsomes
B) microsomal glucose-6-phosphate transporter
C) cytosolic glucose 6-phosphatase
D) microsomal glucose transporter
E) microsomal phosphate transporter

Answer 1

microsomal glucose-6-phosphate transporter

Question 2

You are examining a 5-month-old infant who was brought to your office by distressed parents. Their infant has demonstrated progressive weakness and difficulty eating and appears to have a bulging abdomen. Upon examination, you find striking hypotonia and demonstrable palpable liver. Chest x-ray indicates prominent cardiomegaly. Before a correct diagnosis could be made, the infant lapses into a coma and dies. At autopsy, the heartwas sectioned and stained with the result shown. Which of the following diseases is most likely given the symptoms and outcomes?

A) Andersen disease
B) Cori (Forbes) disease
C) McArdle disease
D) Pompe disease
E) von Gierke disease

Answer 2

Pompe disease

Question 3

Regulation of glycogen metabolism is tightly controlled at the level of the activity of glycogen phosphorylase. Which of the following is known to act as a negative effector of the phosphorylated (most active) form of glycogen phosphorylase?

A) AMP
B) cAMP
C) Ca₂₊
D) glucose 6-phosphate
E) protein kinase A

Answer 3

D
EXPLANATION: Glycogen homeostasis is controlled by regulating the rate of glycogen synthesis and breakdown. Release of glucose from stored glycogen is the role of glycogen phosphorylase (generally just called phosphorylase). The rate of glucose liberation from glycogen by phosphorylase is controlled primarily by short-term phosphorylation and dephosphorylation events. When phosphorylase is phosphorylated by glycogen synthase-phosphorylase kinase (generally just called phosphorylase kinase), it is more active in releasing glucose. This phosphorylation occurs in hepatocytes when stimulation by glucagon leads to increased activity of PKA, which in turn phosphorylates, and activates, phosphorylase kinase. Active phosphorylase liberates glucose 1-phosphate from glycogen which is converted to glucose 6-phosphate. The glucose 6-phosphate is either oxidized in the glycolytic pathway or the phosphate is removed by glucose 6-phosphatase and the free glucose flows into the blood. When glucose-6-phosphate levels rise in hepatocytes, due to reduced utilization, it acts as an allosteric inhibitor of the phosphorylated and active form of phosphorylase.

Question 4

Cyclic AMP-independent activation of glycogen breakdown in hepatocytes occurs as a result of the binding of which of the following?

A) epinephrine to α1-adrenergic receptors
B) epinephrine to β-adrenergic receptors
C) glucagon to its receptor
D) insulin to its receptor

Question 5

An increase in the level of glucose 6-phosphate is expected to have which of the following effects on carbohydrate metabolism in hepatocytes?

A) activation of glycogen phosphorylase-a
B) activation of glycogen synthase-a
C) activation of glycogen synthase-b
D) inhibition of glycogen phosphorylase-b
E) inhibition of glycogen synthase-phosphorylase kinase

Question 6

Epinephrine, released in response to exercise, will lead to phosphorylation events that will ultimately exert which of the following effects on hepatic glycogen metabolism?

A) activation of adenylate kinase
B) activation of glycogen synthase
C) activation of phosphorylase kinase
D) inhibition of glycogen phosphorylase
E) inhibition of glycogen synthase kinase-3 (GSK-3)

Question 7

Muscle membrane will depolarize in response to acetylcholine binding its receptors at the neuromuscular junction. Associated with this depolarization are changes in glycogen metabolism in skeletal muscle cells. Which of the following represents the correct changes in enzyme activity seen in response to acetylcholine binding?

A) decreased glycogen phosphorylase kinase activity due to an increase in calcium binding to its calmodulin subunit
B) decreased phosphorylation of, and inhibited activity of, glycogen phosphorylase kinase
C) increased glycogen phosphorylase kinase activity due to an activation of phosphoprotein phosphatase
D) increased glycogen phosphorylase kinase activity due to an increase in calcium binding to its calmodulin subunit
E) increased phosphorylation of, and inhibited activity of, glycogen phosphorylase kinase

Question 8

An increase in the state of phosphorylation, in hepatocytes in response to glucagon action, will be most accurately reflected by which of the following statements?

A) glycogen phosphorylase activity will be increased
B) PFK-1 activity will be unaffected
C) PFK-2 will exhibit an increased level of kinase activity
D) phosphorylase kinase activity will be decreased
E) phosphoprotein phosphatase-1 activity will be increased

Question 9

Which of the following statements correctly defines the situation under conditions of low blood glucose?

A) a reversal of the muscle hexokinase reaction converts glucose 6-phosphate to glucose for oxidation in glycolysis
B) hepatic glycogen releases glucose in response to insulin-mediated dephosphorylation of glycogen phosphorylase
C) hepatic glycogen releases glucose through a reversal of the glycogen synthase reaction
D) phosphorylation of hepatic glycogen synthase prevents glucose incorporation into glycogen
E) the activity of muscle glycolysis is inhibited by the phosphorylation of PFK-1

Question 10

A 7-year-old boy is examined by his pediatrician because of complaints of severe cramping pain in his legs whenever he rides his bike. In addition, he experiences nausea and vomiting during these attacks. The child has noted that the severity of the cramps is most intense after dinners that include baked potatoes or pasta and sometimes bread. Clinical studies undertaken following a treadmill test demonstrate myoglobinuria, hyperuricemia, and increased serum bilirubin. Which of the following enzyme deficiencies is associated with these clinical findings?

A) glucose 6-phosphatase
B) glycogen synthase
C) liver glycogen debranching enzyme
D) lysosomal acid maltase
E) muscle PFK1

Question 11

A 6-month-old infant who is failing to thrive is brought to your clinic. Tests reveal hepatosplenomegaly, muscle weakness and atrophy, hypotonia, and decreased deep tendon reflexes. Blood tests reveal that the infant has normal glucose levels. Biopsy of the liver reveals initial stages of cirrhosis due to the accumulation of an abnormal glycogen with few branch points whose structure resembles amylopectin. The clinical and laboratory results presented are indicative of which GSD?

A) Andersen disease (type IV glycogen storage disease)
B) Cori or Forbes disease (type III glycogen storage disease)
C) McArdle disease (type V glycogen storage disease)
D) Tarui disease (type VII glycogen storage disease)
E) von Gierke disease (type I glycogen storage disease)

Question 12

A 4-month-old White male infant with a temperature of 38.4°C is examined by his pediatrician. His mother indicates that he has had the fever for the past 4 days, been listless, vomiting, and has watery stools. Blood work indicates the infant is hypoglycemic but this condition does not respond to either epinephrine or glucose administration. In addition, his blood pH is slightly acidic and shows reduced bicarbonate. Other untoward blood chemistry includes elevated triglycerides, cholesterol, and liver enzymes. The child has a protuberant abdomen, thin extremities, and a doll-like face. The pediatrician suspects a specific condition and orders a liver biopsy to test for the activity of which of the following enzyme activities?

A) glucose 6-phosphatase
B) glycogen synthase
C) muscle phosphofructokinase
D) muscle phosphorylase
E) pyruvate kinase

Question 13

Synthesis of glycogen is inhibited in hepatocytes in response to glucagon stimulation primarily as a result of which of the following?

A) a decrease in the level of phosphoprotein phosphatase
B) a decrease in the level of phosphorylated phosphorylase kinase
C) a decrease in the levels of phosphorylated phosphoprotein phosphatase inhibitor-1
D) an increase in the level of the dephosphorylated form of glycogen synthase
E) an increase in the level of the phosphorylated form of glycogen synthase

Question 14

An 8-month-old female infant has died due to cardiorespiratory failure. Physical findings that were apparent prior to her death included feeding difficulties, cardiomegaly, macroglossia, mild hepatomegaly, hypotonia, and a rapidly progressing muscle weakness. Autopsy findings demonstrated marked intralysosomal accumulation of glycogen of normal structure in cardiac and skeletal muscle. These physical and clinical findings are consistent with which of the following glycogen storage diseases?

A) Anderson disease
B) Cori (or Forbes) disease
C) McArdle disease
D) Pompe disease
E) Tarui disease

Question 15

Which of the following shows the correct effects of hormones, when increased in serum, on liver glycogen content?

A) Catecholamines: decreased
Glucocorticoids: decreased
Glucagon: decreased
B) Catecholamines: decreased
Glucocorticoids: decreased
Glucagon: increased
C) Catecholamines: decreased
Glucocorticoids: increased
Glucagon: decreased
D) Catecholamines: increased
Glucocorticoids: decreased
Glucagon: increased
E) Catecholamines: increased
Glucocorticoids: increased
Glucagon: decreased

Question 16

Which of the following enzymes is activated by dephosphorylation?

A) glucose 6-phosphatase
B) UDP-glucose pyrophosphorylase
C) glycogen phosphorylase
D) glycogen synthase
E) phosphoglucomutase

Question 17

After fasting for 8 to 12 hours, the amount of glucose in the hepatic portal vein is markedly lower than the amount after a meal, but the amount in the systemic circulation remains near the normal level. Hepatocytes are able to maintain systemic
Glucose homeostasis in this situation primarily by gluconeogenesis and which of the following biochemical mechanisms?

A) activation of lactase
B) glycogenolysis
C) glycolysis
D) pentose phosphate pathway

Question 18

During the past 3 years, a 20-year-old man has had increasing fatigue and muscle pain in his legs after jogging. Following exercise of his left upper arm, the lactate concentration remains decreased in blood obtained from a vein draining the exercised muscle. A deficiency is most likely in which of the following enzyme activities in the muscle?

A) fructose 1,6-bisphosphatase
B) fructose 1-phosphate aldolase
C) glucose 6-phosphatase
D) glycogen phosphorylase
E) pyruvate carboxylase

Question 19

A 28-year-old man who recently received an injection of epinephrine following a bee sting now has hyperglycemia. The most likely cause is an increase in which of the following processes?

A) absorption of carbohydrate from the digestive tract
B) hepatic glycogenesis
C) hepatic glycogenolysis
D) proteolysis in muscle and release of amino acids
E) synthesis of glucose from fat

Question 20

Patients with an inherited deficiency of phosphorylase in skeletal muscle (McArdle disease) have decreased ability to derive energy from which of the following?

A) glucose
B) glycerol
C) glycogen
D) lactate
E) pyruvate

Question 21

A 27-year-old man has an 11-year history of intermittent muscle pain, weakness, and stiffness following exercise. During exercise, serum lactate concentration does not increase. The most likely explanation for these findings is a deficiency of which of the following in muscle?

A) adenosine
B) calcium
C) glucose-6-phosphatase activity
D) inorganic phosphate
E) phosphorylase activity

Question 22

Which of the following is most likely to result from an increased concentration of intracellular cAMP in skeletal muscle?

A) decreased activity of the TCA cycle
B) increased rate of glycogenolysisCarbohydrates: Glycogen Metabolism Chapter 14 181
C) increased synthesis of glycogen
D) inhibition of phosphofructokinase (PFK1)
E) rapid gluconeogenesis

Question 23

The following reaction (where n represents the number of glucosyl residues), catalyzed by an enzyme activated by AMP, is essential for the mobilization of hepatic glycogen. In the equation,X and Y correspond to which of the following?
Glycogen_(n) + X → Glycogen_(n-1) +Y

A) AMP and glucose
B) ATP and ADP
C) ATP and glucose 6-phosphate
D) H₂O and glucose
E) inorganic phosphate and glucose 1-phosphate

Question 24

A 24-year-old man comes to his doctor because of a 3-month history of pain in the arms and legs after strenuous exercise. He also had severe cramps and passed red urine after digging out several bushes from his front yard. Physical examination now shows abnormalities. This patient most likely has an inherited deficiency in which of the following enzymes?

A) glucocerebrosidase
B) glucose 6-phosphatase
C) hexosaminidase A
D) muscle phosphorylase
E) sphingomyelinase

Question 25

A 25-year-old woman has just finished 30 minutes of vigorous weight lifting, which included several sets of squats. Which of the following substances has decreased most significantly in muscle cells of her thighs?

A) calcium
B) carbon dioxide
C) glycogen
D) lactate
E) myoglobin

Question 26

When glucose is incorporated into liver glycogen, which of the following is required as the direct glucosyl donor?

A) ADP glucose
B) CDP glucose
C) glucose 1-phosphate
D) sucrose
E) UDP glucose

Question 27

A healthy 25-year-old man participates in a clinical study to determine glycogen stores after an 8-hour overnight fast. In preparation for the study, he follows a high-carbohydrate diet for 3 days. In the morning, he receives an injection of glucagon, which results in a significant increase in his serum glucose concentration. Which of the following best describes a reaction that would occur during the breakdown of hepatic glycogen to glucose in this patient?

A) debranching enzyme catalyzes the transfer of an oligomeric sugar unit from one glycogen branch to another
B) glucose 6-phosphate is converted to glucose 1-phosphate
C) glucose 6-phosphate plus ADP yields glucose plus ATP by hexokinase
D) α-1,6-glucosidase catalyzes the cleavage of glucose 1,6-bisphosphate

Question 28

A 20-year-old man comes to the physician because of progressive, painful muscle cramps and intolerance to exercise during the past 3 months. On one occasion, he passed burgundy-colored urine. His serum lactate concentration does not increase in blood from the vein proximal to an exercised right forearm. A biopsy specimen of muscle shows an increased concentration of glycogen. Which of the following enzymes is most likely deficient in this patient's muscle?

A) debrancher enzyme
B) glucose 6-phosphatase
C) α-1,4-glucosidase
D) glycogen phosphorylase
E) UTP-dependent pyrophosphorylase

Question 29

A 27-year-old man has been preparing for a marathon. As part of his normal prerace routine, he consumes a large meal consisting of pasta and mashed potatoes the night before the race. Which of the following enzymes is most likely to be stimulated in his hepatocytes, resulting in increased glycogen stores in this man?

A) glucokinase
B) glucose 6-phosphatase
C) glycogen phosphorylase
D) hexokinase
E) lactate dehydrogenase

Question 30

A 9-month-old infant has a 6-month history of progressive muscle weakness and congestive heart failure with a markedly enlarged heart. She can no longer roll over, is flaccid, and her head flops back when she is lifted. She remains alert and interested in her environment. A muscle biopsy shows increased glycogen particles in lysosomes. The most likely cause of these symptoms is a deficiency of which of the following enzymes?

A) acid maltase
B) glucose 6-phopshatase
C) α-glucosidase
D) muscle PFK1
E) muscle phosphorylase

Question 31

A 19-year-old man comes to the physician because of muscle cramping that began after he participated in a race 24 hours ago. He has had similar but mild symptoms since adolescence that have progressed in severity since he joined a college track team. Physical examination shows no abnormalities. No significant lactate concentration increase is observed in blood obtained distal to an exercised ischemic right arm. A deficiency of which of the following in muscle is the most likely cause of this patient's symptoms?

A) acid maltase
B) carnitine
C) debranching enzyme
D) glucose 6-phosphatase
E) glycogen phosphorylase

Question 32

A 2-year-old girl is brought to the physician because of irritability and failure to thrive. Physical examination shows hepatomegaly. Laboratory studies show mild fasting hypoglycemia. A high-protein diet or intravenous administration of fructose results in an increased serum glucose concentration. Biopsy of hepatic tissue shows increased amounts of glycogen with short outer branches. The most likely cause of her condition is a defect in which of the following?

A) debranching enzyme
B) glucokinase
C) glucose 6-phosphatase
D) glycogen phosphorylase
E) glycogen synthase

Question 33

A healthy subject who fasts for 24 hours is most likely to have a decrease in which of the following?

A) hepatic glycogenesis
B) ketone body formation
C) plasma cortisol concentration
D) plasma glucagon concentration
E) renal gluconeogenesis

Question 34

Analysis of a tissue sample obtained on biopsy of the liver in a patient with GSD shows normal activities of glycogen phosphorylase, glycogen debranching enzyme, and glucose 6-phosphatase. A defect in the signal transduction pathway for glycogen metabolism is suspected. Which of the following enzymes is most likely to be defective?

A) glycogen branching enzyme
B) glycogen synthase
C) hexokinase
D) phosphorylase phosphatase
E) phosphorylase kinase

Question 35

When serum glucose concentrations are decreased, glucagon is released from the pancreas and binds to a receptor on hepatic cell membranes. As a result, hepatic glycogen synthesis is inhibited. By which of the following mechanisms is glycogen synthase modified to cause this inhibition?

A) allosteric inhibition by bound AMP
B) binding of intracellular glucose 1-phosphate with a lower K_m
C) dephosphorylation by a glucagon-dependent phosphatase
D) increased amounts of the enzyme due to the CREB protein
E) phosphorylation on serine residues

Question 36

A 4-month-old girl with a 1-month history of poor head control and progressive muscle weakness is brought to the physician for a follow-up examination. Physical signs show a large tongue, hepatomegaly, and severe generalized hypotonia. A chest x-ray shows cardiomegaly. She dies of cardiac failure at the age of 10 months. Autopsy shows a markedly enlarged globular heart, hepatomegaly, and glycogen in the skeletal muscle, heart, and liver. This patient most likely had a deficiency in which of the following?

A) acid α-glucosidase
B) branching enzyme
C) debranching enzyme
D) glucose 6-phosphatase
E) hepatic phosphorylase