[2] Lecture 8: Glycogen Metabolism Flashcards Preview

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Flashcards in [2] Lecture 8: Glycogen Metabolism Deck (87)
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61

whenglycogen reaches 11 residues, a fragment of the chain [about 7 residues long] is broken off at an alpha-1,4 link and reattached elsewhere through an alpha-1,6 link by activity of what enzyme?

Glucosyl (4:6) transferase

62

The new branching point must be at least ___ residues away from a preexisting branch

4

63

What are the 2 reasons for branching of glycogen?

1. Increases solubility
2. Increases number of terminal non-reducing ends

Increases rate at which glycogen can be synthesized and degraded

64

Key enzyme in glycogen synthesis

Glycogen synthase

65

2 forms of glycogen synthase

One form in the liver

One form in the muscles and other tissues

66

Active [non-phosphorylated] form = a form

Inactive [phosphorylated] b form

Interconversion mediated by covalent modifications [fine-tuning role]. What is this regulation?

Regulation of glycogen synthesis

67

Glycogen synthesis is regulated by what enzyme that phosphorylates?

Glycogen synthase kinase
-GSK

68

What hormones affect GSK?

Allosteric regulation?

Insulin and PKA

Allosteric: glucose-6-phosphate [powerful activator]- stabilizes the R state

69

Synthesis and degradation of glycogen pathways are:

Independent

Allows for independent regulation.

70

The 2 key enzymes to glycogen metabolism:

Glycogen phosphorylase (GP)

Glycogen synthase

Both are the rate limiting steps of degradation/synthesis

Both enzymes are regulated by reversible phosphorylation but effects are in opposite directions

71

How do glucagon and epi control both glycogen breakdown and synthesis?

Via PKA!

72

What is the centerpiece intermediate in glycogen metabolism?

PKA

73

GP function

Stimulate glycogen breakdown

74

Glycogen synthase function:

Stimulate glycogen synthesis.

75

What is favored in fed state: glycogenolysis or glycogenesis:

Glycogenesis

B/c BG and insulin elevated and cellular ATP is high- signal of high energy

-when glycogen synthesis is favored, the DEPHOSPHO form of glycogen synthase (active) and glycogen phosphorylase(inactive) are predominant

76

What is favored in fasting state: glycogenolysis or glycogenesis:

Glycogenolysis

B/c BG levels are low and glucagon levels are high and cellular Ca++ and AMP are elevated -like exercise

-when glycogen degradation is favored PHOSPHORYLATED forms of glycogen synthase (inactive) and glycogen phosphoylase (active) are predominant

77

High BG

Release of _____ by beta cells of pancreas

Binding to its receptor tyrosine kinase

Activation of signaling cascade

Regulation by insulin; insulin

78

4 key proteins in Regulation by insulin:

-GLUT 4 [glu transporter]
-Protein kinase B [PKB]
-Protein phosphatase 1 [PP1]
-Glycogen synthase kinase 3 [GSK3]

79

Net result of insulin

Activation of glycogen synthase and inactivation of glycogen phosphorylase

80

Formation of insulin receptor complex i activated by:

Protein kinase B
[PKB]

This also translocates GLUT to membrane

81

What phosphorylates PP1 (active) and GSK3 (inactive)

PKB

82

What is function of PP1

Active PP1 dephosphorylates glycogen synthase (activates it)

And

Dephosphorylates glycogen phosphorylase (GP-deactivating it)

83

-Reduced sensitivity to insulin
-Called insulin resistance
-Mutations in insulin receptor and/or downstream signaling proteins

-Down-regulation in receptor levels triggered by elevated insulin [leading 2 endocytosis and degradation of the insulin receptor].notreplaced by translation

What type disorder is this?

Type II diabetes

84

What is the glucose sensor in the liver cells?

Glycogen phosphorylase

85

Glucose has what effect when bound to liver GP (a)?

Deactivates it and allows glycogen synthase to begin storing energy...b/c it is in fed state or high energy

86

McArdle syndrome is a disease of:

Muscle GP

Limited ability to perform strenuous exercise b/c of painful muscle cramps; otherwise patient is normal.

87

Hers disease is:

Liver GP issue

Milder form of liver enlargement, FTT, hypoglycemia, ketosis, hyperuricemia, hyperlipidemia