Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Biochemistry > Lecture 23, Glyc Metabolism II (Zaidi) > Flashcards

Lecture 23, Glyc Metabolism II (Zaidi) Flashcards

1
Q

Why is the regulation of glycogen metabolism important?

A

Maintain blood sugar and provide energy to muscles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

T or F: The pathways of glycogen metabolism synthesis and degradation are independent.

A

True.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What allows for the separate regulation of glycogen metabolism?

A

Pathways of synthesis and degradation are independent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the 2 key enzymes of glycogen metabolism?

A

Glycogen synthase and glycogen phosphorylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which enzyme is the rate limiting step on glycogen metabolism synthesis?

A

Glycogen synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which enzyme is the rate limiting step on glycogen metabolism degradation?

A

Glycogen phosphorylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How are glycogen synthase and glycogen phosphorylase regulated? What is this under the control of?

A

By allosteric regulators and by reversible phosphorylation (effects are in opposite directions); Under the control of hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the 2 forms that glycogen synthase exists in?

A

Active, non-phosphorylated A form; Inactive, phosphorylated B form

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the interconversion of the 2 forms of glycogen synthase mediated by?

A

Covalent modification

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which enzymes phosphorylates glycogen synthase?

A

Several kinases, but most importantly glycogen synthase kinase (GSK)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is GSK under the control of?

A

Insulin and PKA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the relationship between G6P and glycogen synthesis?

A

G6P provides allosteric regulation of glycogen synthase (powerful activator); Stabilizes the active form of the enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the 2 forms that glycogen phosphorylase exists in?

A

Active A form (relaxed) in liver; Inactive B form (tense) in muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

T or F: The isozymes of glycogen phosphorylase exist in excess of R and small amounts of T.

A

False. Both isozymes of glycogen phosphorylase exist in equilibrium between R and T.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is glycogen phosphorylase regulated by?

A

Several allosteric effectors (signal energy state of cell) and reversible phosphorylation (responsive to hormones)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why is GP called an isozyme?

A

GP in the liver and in the muscle are the products of separate genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How does GP different in the liver and the muscle?

A

In sensitivity to regulatory molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe the activation of liver GP.

A

Inactivated by free glucose (indicator of blood sugar levels), unaffected by AMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Describe the activation of muscle GP.

A

Allosterically activated by AMP (measure of low energy status of cell)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is Hers disease caused by?

A

Mutation in liver GP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is McArdle syndrome caused by?

A

Mutation in muscle GP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe the allosteric regulation of liver GP.

A

Default A (active) form, inactivated by glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How is liver GP inactivated by glucose?

A

Glucose binds to active site and stabilizes conformation in the T (inactive) state; When glucose levels are high, there is no need for glycogen breakdown

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Describe the allosteric regulation of muscle GP.

A

Default B (inactive) form, activated by AMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How is muscle GP activated by AMP?

A

Binds to active site and stabilizes conformation of B in R (active) state; During muscle concentration, ATP is converted to AMP by myosin and adenylate kinase signaling to the GP to breakdown glycogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is the relationship between ATP and G6P with the allosteric regulation of muscle GP?

A

Negative allosteric regulators; Under normal physiological conditions, GP is inactive because of the inhibitory effect of ATP and G6P

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Which process of glycogen metabolism is favored in the fed state?

A

Glycogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Describe the “fed state.”

A

Blood glucose high, insulin high, cellular ATP high

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

When glycogen synthesis is favored, which enzyme states of glycogen metabolism are predominant?

A

Dephosphorylated form of glycogen synthase (active), dephosphorylated form of glycogen phosphorylase (inactive)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Describe the “fasting state.”

A

Blood glucose low, glucagon high

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Which process of glycogen metabolism is favored in the fasting state?

A

Glycogenolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

In which 2 states is glycogenolysis favored?

A

Fasting state and during exercise

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Describe the state of the body during exercise.

A

Cellular calcium high (in exercise muscles), AMP high (from breakdown of ATP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

When glycogen breakdown is favored, which enzyme states are predominant?

A

Phosphorylated form of glycogen synthase (inactive), phosphorylated form of glycogen phosphorylase (active)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Which cells in the body release insulin?

A

Beta cells of pancreas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What kind of receptor is the insulin receptor?

A

RTK

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are the 4 key proteins in the activation of the signaling cascade in the regulation of insulin?

A

GLUT4, PKB, PP1, GSK3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is PKB?

A

Protein kinase B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What is PP1?

A

Protein phosphate 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is GSK3?

A

Glycogen synthase kinase 3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

After activation of the signaling cascade in the regulation of insulin, outline what happens.

A

Formation of the insulin receptor complex, activation of PKB, translocation of GLUT4 to the membrane, PKB phosphorylated PP1 and GSK3, glycogen synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What does PKB phosphorylate?

A

PP1 and GSK3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What does active PP1 do?

A

Dephosphorylates glycogen synthase and dephosphorylates glycogen phosphorylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What is the net result of the mechanism of regulation of insulin?

A

Glycogen synthesis via activation of glycogen synthase and inactivation of glycogen phosphorylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Type 2 diabetes is also called ___ ___.

A

Insulin resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What is the pathology of T2D?

A

Reduced sensitivity to insulin because of mutations in insulin receptor/downstream signaling proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Describe the down-regulation in receptor levels in T2D.

A

Triggered by elevated insulin, endocytosis and degradation of the insulin receptor, defective receptors not replaced by translation

48
Q

What is normal blood glucose criteria?

A

70-100 mg/dL (fasting); =< 140 mg/dL (fed)

49
Q

What is prediabetic/at risk blood glucose criteria?

A

100-125 mg/dL (fasting); > 140 mg/dL (fed)

50
Q

What is the blood glucose criteria for diabetes mellitus?

A

> = 126 mg/dL (fasting); >= 199 mg/dL (fed)

51
Q

In the hormonal control of GP, what do low blood sugar levels release?

A

Glucagon (acts on liver)

52
Q

In the hormonal control of GP, what does muscle activity release?

A

Epinephrine (effects are on the muscle)

53
Q

In the hormonal control of GP, what are the effects of the hormones mediated by?

A

GPCR

54
Q

What do epinephrine and glucagon signal in the hormonal control of GP?

A

Glycogen breakdown

55
Q

What does the phosphorylation of a single serine residue covert?

A

B to A

56
Q

In the conversion of B to A by phosphorylation, what is the conversion initiated by?

A

Hormones

57
Q

T or F: Phosphorylation is carried out by phosphorylase kinase.

A

True.

58
Q

In regard to the regulation of glycogen, what do low blood glucose levels promote?

A

Glycogen breakdown

59
Q

Which cells in the pancreas release glucagon?

A

Alpha cells

60
Q

Glucagon binds the GPCR on which cells? What does this trigger?

A

Hepatocytes; Triggers signaling cascade

61
Q

What are the key enzymes and second messengers in the regulation by glucagon?

A

G protein, AC and cAMP, PKA, PP1, PK

62
Q

Outline the signaling cascade that has been triggered in the regulation by glucagon after the glucagon binds the GPCR on hepatocytes.

A

Glucagon binds to GPCR and turns on G protein, activates AC which forms cAMP, activates PKA, PKA phosphorylates glycogen synthase (inactivated), PKA phosphorylates PK (active), PKA phosphorylates an inhibitor which inactivates PP1, active PK phosphorylates glycogen phosphorylase (active), glycogen breakdown

63
Q

What is the net result of the signaling cascade of the regulation by glucagon?

A

Glycogen breakdown (via inactivation of glycogen synthase and activation of glycogen phosphorylase)

64
Q

What is epinephrine released by?

A

Adrenal glands

65
Q

What does epinephrine promote the degradation of? What is this similar to?

A

Glycogen; Pathway is similar to glucagon

66
Q

Describe what the allosteric regulators of epinephrine are.

A

G6P, free glucose, calcium, AMP

67
Q

How is G6P an allosteric regulator of epinephrine?

A

Activates glycogen synthase, inactivates glycogen phosphorylase

68
Q

How is free glucose an allosteric regulator of epinephrine?

A

Inhibits glycogen phosphorylase in liver but not in muscle

69
Q

How is calcium an allosteric regulator of epinephrine?

A

Activates glycogen phosphorylase kinase

70
Q

How is AMP an allosteric regulator of epinephrine? When is this especially relevant?

A

Activates glycogen phosphorylase; Especially relevant during periods of exercise

71
Q

When does glycogen metabolism stop?

A

When secretion of hormone stops

72
Q

What happens to glycogen metabolism after the secretion of hormone stops?

A

PK and GP are dephosphorylated and inactivated, breakdown of glycogen stops, synthesis of glycogen promoted

73
Q

What is the fate of liver Glu1P?

A

Glu1P is converted to glu6P and then to glucose by G6P; Glucose released into the blood stream

74
Q

What is the fate of muscle glu1P?

A

Use glu6P to generate energy via glycolysis and the TCA cycle

75
Q

What can’t myocytes hydrolyze glu6P?

A

Lack G6P

76
Q

What enzymes is the glucose sensor in liver cells?

A

Glycogen phosphorylase

77
Q

What is the defective enzyme in Von Gierke (type I) disease?

A

Glucose 6-phosphatase or the transport system

78
Q

What is the organ affected in Von Gierke (type I) disease?

A

Liver and kidney

79
Q

How is glycogen affected in the organ in Von Gierke (type I) disease?

A

Increased amount, but normal structure

80
Q

What is the defective enzyme in Pompe (type II) disease?

A

alpha-1,4-glucosidase (lysosomal)

81
Q

What is the organ affected in Pompe (type II) disease?

A

All organs

82
Q

How is glycogen affected in the organ in Pompe (type II) disease?

A

Massive increase in amount, but normal structure

83
Q

What is the defective enzyme in Cori (type III) disease?

A

alpha-1,6-glucosidase

84
Q

What is the organ affected in Cori (type III) disease?

A

Muscle and liver

85
Q

How is glycogen affected in the organ in Cori (type III) disease?

A

Increased amount and short outer branches

86
Q

What is the defective enzyme in Andersen (type IV) disease?

A

GLucosyl (4:6) transferase (branching enzyme)

87
Q

What is the organ affected in Andersen (type IV) disease?

A

Liver and spleen

88
Q

How is glycogen affected in the organ in Andersen (type IV) disease?

A

Normal amount, but very long outer branches

89
Q

What is the defective enzyme in McArdle (type V) disease?

A

Phosphorylase

90
Q

What is the organ affected in McArdle (type V) disease?

A

Muscle

91
Q

How is glycogen affected in the organ in McArdle (type V) disease?

A

Moderately increased amount and normal structure

92
Q

What is the defective enzyme in Hers (type VI) disease?

A

Phosphorylase

93
Q

What is the organ affected in Hers (type VI) disease?

A

Liver

94
Q

How is glycogen affected in the organ in Hers (type VI) disease?

A

Increased amount

95
Q

What is the defective enzyme in Type VII glycogen storage disease?

A

Phosphofructokinase

96
Q

What is the organ affected in Type VII glycogen storage disease?

A

Muscle

97
Q

How is glycogen affected in the organ in Type VII glycogen storage disease?

A

Increased amount and normal structure

98
Q

What is the defective enzyme in Type VIII glycogen storage disease?

A

Phosphorylase kinase

99
Q

What is the organ affected in Type VIII glycogen storage disease?

A

Liver

100
Q

How is glycogen affected in the organ in Type VIII glycogen storage disease?

A

Increased amount and normal structure

101
Q

Which of the glycogen storage diseases are inherited in an autosomal recessive manner?

A

Types I-VII

102
Q

How is type VIII glycogen storage disease inherited?

A

Sex-linked

103
Q

T or F: Types III-VIII glycogen storage diseases are inherited in an autosomal dominant manner.

A

False. Types I-VII are inherited in an autosomal recessive manner, while type VIII is sex-linked.

104
Q

In GSD type 0, what is the defective enzyme?

A

Glycogen synthase

105
Q

How is glycogen affected in GSD 0 disease?

A

Patients cannot synthesize glycogen

106
Q

What is the presentation and treatment of GSD 0?

A

Patients have muscle cramps due to lack of glycogen in muscle; Rely on glucose in diet, vulnerable to hypoglycemia when fasting (during sleep), must eat frequently

107
Q

What is the clinical presentation of GSD type III (Cori)?

A

Light hypoglycemia and heptomegaly

108
Q

What is the life expectancy of a patient with GSD type IV (Andersen)?

A

5 years

109
Q

Which GSD is a result of a deficiency in the rate-limiting step of glycogen breakdown?

A

GSD V (McArdle)

110
Q

What is the clinical presentation of GSD type V (McArdle)?

A

Patients are unable to supply muscles with enough glucose, have weakness, muscle cramps, exercise intolerance, myoglobinuria; Tolerance by reducing strenuous exercise

111
Q

Describe blood glucose levels in patients with GSD VI (Hers)?

A

Low blood glucose levels

112
Q

What can be used to treat GSD type II (Pompe)?

A

Enzyme replacement therapy (ERT)

113
Q

Describe ERT to treat GSD II.

A

Recombinant human alpha-glucosidase delivered via IV infusion in babies/young children

114
Q

What is the clinical presentation of GSD II?

A

Progressive muscle weakness and myopathy (including heart and skeletal muscle)

115
Q

What do patients typically die of with GSD II?

A

Heart failure

Biochemistry (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions