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BMS 610 Exam 3 > Chapter 15 - Glycogen Metabolism & Regulation > Flashcards

Chapter 15 - Glycogen Metabolism & Regulation Flashcards

1
Q

What is glycogen, and where is it primarily stored in animals?

A

A polymeric form of glucose stored mainly in the liver and muscle.

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2
Q

What is the difference between α- and β-granules in glycogen?

A

α-granules are larger clusters of β-granules, visible in the liver after feeding.

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3
Q

What is glycogenolysis?

A

The process of breaking down glycogen to glucose-1-phosphate.

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4
Q

Define glycogenesis.

A

The synthesis of glycogen from glucose.

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5
Q

Which enzyme catalyzes the breakdown of glycogen in glycogenolysis?

A

Glycogen phosphorylase.

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6
Q

What is the role of phosphoglucomutase in glycogen metabolism?

A

Converts glucose-1-phosphate to glucose-6-phosphate for glycolysis or release into the blood.

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7
Q

How does glycogen breakdown differ between muscle and liver?

A

In muscle, glucose-6-phosphate enters glycolysis; in liver, it can be converted to glucose to maintain blood sugar levels.

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8
Q

What is the role of UDP-glucose in glycogenesis?

A

It donates glucose units to extend the glycogen chain.

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9
Q

Describe the function of glycogenin in glycogen synthesis.

A

Acts as a primer for glycogen synthesis, catalyzing the addition of initial glucose residues.

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10
Q

How does glycogen phosphorylase regulation differ in muscle and liver?

A

In muscle, it responds to AMP and Ca²⁺ for energy demand; in liver, it responds to glucose and hormones like glucagon.

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11
Q

How is glycogen synthase regulated?

A

Activated by insulin and glucose-6-phosphate, inactivated by phosphorylation.

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12
Q

What role does cAMP play in glycogen breakdown?

A

Activates a cascade leading to glycogen phosphorylase activation, promoting glycogenolysis.

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13
Q

Explain the role of Ca²⁺ in muscle glycogenolysis.

A

Activates phosphorylase kinase, which then activates glycogen phosphorylase.

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14
Q

What effect does AMP have on glycogen phosphorylase in muscle?

A

Activates glycogen phosphorylase, increasing glucose release during high energy demand.

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15
Q

How does insulin influence glycogen synthesis?

A

Insulin activates glycogen synthase by inactivating GSK3 and increasing PP1 activity.

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16
Q

Describe the role of glucagon in glycogen metabolism in the liver.

A

Stimulates glycogen breakdown to increase blood glucose levels.

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17
Q

How does epinephrine affect glycogen metabolism in muscle?

A

Stimulates glycogen breakdown for rapid ATP production during ‘fight or flight’ response.

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18
Q

What is the effect of glucose on liver glycogen phosphorylase?

A

Glucose binding promotes dephosphorylation and inactivation of glycogen phosphorylase.

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19
Q

Describe the enzyme cascade activated by cAMP in glycogenolysis.

A

cAMP activates PKA, which activates phosphorylase kinase, leading to activation of glycogen phosphorylase.

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20
Q

What is the role of phosphoprotein phosphatase 1 (PP1) in glycogen metabolism?

A

PP1 dephosphorylates glycogen phosphorylase and glycogen synthase, modulating their activities.

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21
Q

Name a key allosteric inhibitor of muscle glycogen phosphorylase.

A

ATP, which signals sufficient energy and inhibits glycogen breakdown.

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22
Q

What is the difference in glycogen metabolism regulation between muscle and liver?

A

Muscle glycogen breakdown is for ATP, while liver glycogen regulates blood glucose levels.

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23
Q

Describe Type Ia glycogen storage disease and its cause.

A

Caused by glucose-6-phosphatase deficiency, leading to hypoglycemia and glycogen accumulation.

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24
Q

What is Type V glycogen storage disease (McArdle disease)?

A

Caused by muscle glycogen phosphorylase deficiency, resulting in exercise intolerance.

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25
Q

Explain the role of GSK3 in glycogen metabolism.

A

GSK3 phosphorylates and inactivates glycogen synthase, inhibiting glycogenesis.

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26
Q

How does glucose-6-phosphate affect glycogen synthase?

A

Allosterically activates the inactive form, promoting glycogen synthesis.

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27
Q

Describe Pompe disease and its symptoms.

A

Caused by acid maltase deficiency, leading to glycogen accumulation in lysosomes and muscle weakness.

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28
Q

What triggers the activation of glycogen phosphorylase kinase in muscle?

A

Increased calcium levels during muscle contraction.

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29
Q

How does insulin inhibit GSK3?

A

Through signaling pathways that inactivate GSK3, promoting glycogen synthesis.

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30
Q

What is the effect of fasting on liver glycogen metabolism?

A

Fasting increases glucagon, stimulating glycogen breakdown to maintain blood glucose.

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31
Q

How does glycogen branching enzyme function in glycogenesis?

A

It creates α(1→6) branches, increasing glycogen solubility and energy release rate.

32
Q

What is Cori disease (Type III glycogen storage disease)?

A

Caused by deficiency in debranching enzyme, leading to abnormal glycogen with short outer branches.

33
Q

What causes Anderson disease (Type IV glycogen storage disease)?

A

Branching enzyme deficiency, resulting in abnormal, unbranched glycogen.

34
Q

Describe the importance of glucose-6-phosphatase in liver glycogen metabolism.

A

Converts glucose-6-phosphate to free glucose for blood glucose regulation.

35
Q

What enzyme deficiency causes Hers disease (Type VI)?

A

Liver glycogen phosphorylase deficiency, leading to mild hypoglycemia.

36
Q

What role does casein kinase II (CKII) play in glycogen metabolism?

A

Primes glycogen synthase for phosphorylation by GSK3, regulating glycogenesis.

37
Q

How does PP1 activity differ in response to insulin in muscle vs. liver?

A

PP1 is activated by insulin in both, but with a greater effect on liver glycogen synthesis.

38
Q

What is the significance of AMP-activated protein kinase (AMPK) in muscle?

A

Activates energy production pathways, including glycogenolysis, during low energy states.

39
Q

How does the liver sense glucose to regulate glycogen metabolism?

A

Glucose binds to phosphorylase, making it more susceptible to inactivation by PP1.

40
Q

Why is glycogen a preferred storage form of glucose?

A

It is rapidly mobilizable, does not diffuse out of cells, and avoids osmotic issues.

41
Q

How does glycogen synthase add glucose to glycogen?

A

Transfers glucose from UDP-glucose to the non-reducing end of glycogen.

42
Q

Describe the autocatalytic function of glycogenin in glycogen synthesis.

A

Glycogenin catalyzes the addition of glucose residues to its own tyrosine residues, creating a primer for glycogen synthase.

43
Q

How is glucose-1-phosphate formed from glucose-6-phosphate?

A

Through the action of phosphoglucomutase, which transfers a phosphate group.

44
Q

Why is UDP-glucose formation considered irreversible?

A

The release and hydrolysis of pyrophosphate make the reaction energetically favorable.

45
Q

What is the role of glucagon in hepatic glycogen metabolism during fasting?

A

Glucagon activates glycogenolysis, increasing blood glucose levels by promoting glycogen breakdown.

46
Q

How does epinephrine signal glycogen breakdown in muscle?

A

It binds to β-adrenergic receptors, activating a cAMP cascade that activates glycogen phosphorylase.

47
Q

Explain how AMP acts as an allosteric activator in muscle glycogenolysis.

A

AMP binds to glycogen phosphorylase, enhancing its activity to release glucose-1-phosphate during energy demand.

48
Q

What initiates the inactivation of glycogen phosphorylase in liver cells?

A

Glucose binding exposes phosphorylated residues, making it a target for dephosphorylation by PP1.

49
Q

Describe the role of phosphoglucomutase in glucose utilization.

A

Converts glucose-1-phosphate to glucose-6-phosphate for entry into glycolysis or conversion to free glucose in the liver.

50
Q

How does insulin signaling activate glycogen synthase?

A

Insulin inhibits GSK3 and activates PP1, which dephosphorylates and activates glycogen synthase.

51
Q

What is the role of branching enzyme deficiency in Anderson disease?

A

Lack of branching enzyme results in unbranched glycogen, which is poorly soluble and can lead to liver dysfunction.

52
Q

Why does Cori disease result in abnormal glycogen structure?

A

A deficiency in debranching enzyme prevents full glycogen breakdown, creating glycogen with short outer branches.

53
Q

How does glycogen synthase kinase 3 (GSK3) regulate glycogen synthase?

A

GSK3 phosphorylates glycogen synthase, converting it to an inactive form, thus inhibiting glycogen synthesis.

54
Q

What is the function of liver glycogen phosphorylase during hypoglycemia?

A

It breaks down glycogen to maintain blood glucose levels, especially important during fasting.

55
Q

What is McArdle disease, and what symptoms are associated with it?

A

McArdle disease is a muscle glycogen phosphorylase deficiency, leading to exercise intolerance and muscle pain.

56
Q

How is glycogen metabolism regulated differently in liver and muscle tissue?

A

The liver controls blood glucose through glycogen metabolism, while muscle uses glycogen solely for its own energy needs.

57
Q

What initiates the cascade effect in glycogen breakdown upon epinephrine binding?

A

Epinephrine binding increases cAMP, activating PKA, which activates phosphorylase kinase, leading to glycogen phosphorylase activation.

58
Q

Why is ATP an inhibitor of glycogen phosphorylase in muscle?

A

High ATP indicates sufficient energy, thus inhibiting glycogen breakdown to conserve resources.

59
Q

Describe the cascade effect of cAMP on glycogenolysis.

A

cAMP activates protein kinase A (PKA), which phosphorylates and activates phosphorylase kinase, ultimately activating glycogen phosphorylase.

60
Q

How does PP1 facilitate the activation of glycogen synthase?

A

PP1 dephosphorylates glycogen synthase, converting it to its active form for glycogen synthesis.

61
Q

What role does glucose play in the allosteric regulation of liver glycogen phosphorylase?

A

Glucose binding to liver glycogen phosphorylase induces a conformational change, making it more susceptible to inactivation by PP1.

62
Q

Describe the role of protein kinase A (PKA) in glycogen metabolism.

A

PKA phosphorylates enzymes like phosphorylase kinase, initiating glycogenolysis, and inhibits glycogen synthase to prevent glycogenesis.

63
Q

Why is insulin essential for glycogen synthesis?

A

Insulin promotes dephosphorylation of glycogen synthase, activating it to facilitate glucose storage.

64
Q

How does calcium (Ca²⁺) enhance glycogen breakdown in muscle?

A

Ca²⁺ binds to phosphorylase kinase, activating it, which then activates glycogen phosphorylase for glycogenolysis during muscle contraction.

65
Q

What genetic mutation causes Von Gierke disease (Type Ia)?

A

Mutation in glucose-6-phosphatase, leading to impaired blood glucose maintenance and hypoglycemia.

66
Q

How does Type Ib glycogen storage disease differ from Type Ia?

A

Type Ib involves a defect in the glucose-6-phosphate transporter, while Type Ia is a glucose-6-phosphatase deficiency.

67
Q

Explain how the liver regulates blood glucose via glycogen metabolism during fasting.

A

During fasting, glucagon activates glycogen breakdown in the liver, increasing glucose release into the bloodstream.

68
Q

Describe the impact of phosphoprotein phosphatase 1 (PP1) on glycogen breakdown.

A

PP1 dephosphorylates glycogen phosphorylase, reducing its activity and slowing glycogenolysis.

69
Q

How does fasting influence the action of glycogen phosphorylase in the liver?

A

Fasting increases glucagon, activating glycogen phosphorylase and promoting glycogen breakdown for blood glucose maintenance.

70
Q

Why does muscle lack glucose-6-phosphatase, and how does this affect glycogen metabolism?

A

Muscle lacks glucose-6-phosphatase to retain glucose for its own use rather than releasing it into the blood.

71
Q

What is the significance of glycogen branching in energy release?

A

Branching increases the number of non-reducing ends, allowing rapid glucose release during glycogen breakdown.

72
Q

How does liver glycogen metabolism respond to insulin and glucagon?

A

Insulin promotes glycogen synthesis, while glucagon stimulates glycogen breakdown for blood glucose maintenance.

73
Q

What is the impact of glycogen storage diseases on metabolism?

A

They disrupt glycogen synthesis or breakdown, often leading to hypoglycemia, muscle weakness, or organ enlargement.

74
Q

What enzyme deficiency causes Hers disease, and what are its effects?

A

Liver glycogen phosphorylase deficiency, resulting in mild hypoglycemia due to reduced glycogen breakdown in the liver.

75
Q

Explain the role of debranching enzyme in glycogenolysis.

A

It removes branches by transferring glucose residues and hydrolyzing α(1→6) linkages, facilitating glycogen breakdown.

BMS 610 Exam 3 (4 decks)

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