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BIOL 2421 - Cellular Biochem > 18. Glycogen metabolism > Flashcards

18. Glycogen metabolism Flashcards

1
Q

what is the purpose of muscle glycogen

A

provides a quick source of energy for intense aerobic or anaerobic metabolism

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2
Q

what is the purpose of liver glycogen

A

acts as a reserve that can quickly be hydrolyzed and released into the bloodstream upon low blood sugar

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3
Q

T or F: we ingest glycogen in our diet

A

true

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4
Q

how many glycogen residues can make up a single glycogen particle

A

up to 55,000

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5
Q

how much of the liver’s weight can be glycogen

A

up to 10%

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6
Q

how is dietary glycogen broken down

A

hydrolyzed by a-amylases to release glucose, which can then enter glycolysis

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7
Q

what is endogenous glycogen

A

glycogen stored in our muscles or liver

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8
Q

name the three enzymes involved in endogenous glycogen breakdown

A
  • glycogen phosphorylase
  • glycogen debranching enzyme
  • phosphoglucomutase
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9
Q

what is the first thing glycogen phosphorylase does

A

completes a phosphorolysis reaction

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10
Q

where does the phosphorolysis from glycogen phosphorylase happen

A

on a non reducing end of glycogen

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11
Q

what is the result of phosphorolysis on the non reducing end of glycogen

A

removes the terminal glucose

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12
Q

what is the name of the terminal glucose cleaved from the phosphorolysis of the glycogen non reducing end

A

a-D-glucose 1-phosphate

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13
Q

what is a non reducing end

A

it has an anomeric carbon WITHIN a glycosidic linkage

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14
Q

T or F: glycogen phosphorylase will act continuously forever

A

false; it acts continuously on the non reducing ends of glycogen until it reaches a specific position: four glucose residues away from a a1-6 branch point

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15
Q

at what point does glycogen phosphorylase stop

A

when it is four glucose residues away from an a1-6 branch point

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16
Q

once glycogen phosphorylase stops, what enzyme takes over

A

glycogen debranching enzyme

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17
Q

what two types of activity does glycogen debranching enzyme have

A

transferase and glucosidase activity

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18
Q

describe the transferase activity of glycogen debranching enzyme

A

the enzymes transfer the next three glucose residues to a nearby non reducing end, reattaching them with a1-4 linkages

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19
Q

describe the glucosidase activity of glycogen debranching enzymes

A

they cleave the lone glucose remaining at the branch point and it is released as free glucose

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20
Q

once the four glucoses beside the a1-6 branch point have been removed (3 moves and 1 released), what happens

A

glycogen phosphorylase activity can continue! yay

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21
Q

recall that glycogen phosphorylase created G1P molecules by phosphorolysing the non reducing ends of glycogen. What enzyme deals with these molecules?

A

phosphoglucomutase

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22
Q

describe the role of phosphoglucomutase

A

it converts all the free G1P to G6P

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23
Q

what happens to all the G6P created by phosphoglucomutase

A

it can be used in glycolysis, or it can be converted to glucose in GNG so it can leave the cell

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24
Q

describe how G6P is made from phosphoglucomutase

A

the enzyme is phosphorylated on it’s Ser residue. It donates the P to the C6 of glucose, =glucose 1,6-bisphosphate. Then this product donates the P from C1 back to the enzyme (basically they trade P groups)

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25
Q

what happens to G6P in the muscle

A

it can enter glycolysis and serve as an energy source to support muscle contraction

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26
Q

what happens to G6P in the liver

A

it needs to be converted to glucose to be released into the bloodstream to maintain blood sugar between meals

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27
Q

what is the function of glucose 6-phosphatase

A

converts G6P to glucose

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28
Q

where is G6Pase located

A

the liver, embedded in the ER membrane

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29
Q

which side of the ER membrane is the G6Pase active site

A

the luminal side

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30
Q

how many transporters are involved to move G6P, glucose, and Pi across the ER membrane

A

3

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31
Q

describe the movement of G6P, glucose, and Pi across the ER membrane

A

T1 brings G6P into the lumen where it’s converted into glucose and Pi via G6Pase. Both leave the lumen through T2 and T3 respectively. GLUT2 allows glucose to leave the liver cell

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32
Q

what is the benefit of having the G6P–> glucose reaction happen in the ER lumen of the liver

A

if we remove the phosphate in the cytosol, this is the same place as glycolysis, which would immediately add the phosphate back via hexokinase

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33
Q

T or F: glycogen synthesis takes place in all animal tissues

A

true

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34
Q

where is glycogen synthesis prominent

A

liver and skeletal muscles

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35
Q

what is the name of the key enzyme in glycogen synthesis

A

glycogen synthase

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36
Q

describe the use of a sugar nucleotide intermediate in glycogen synthesis

A

the anomeric carbon of a sugar phosphate is attached to an NDP. This primes the molecule, as NMP/NDP will later make a good leaving group

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37
Q

T or F: once the anomeric carbon of a sugar phosphate is attached to an NDP, it can unattach

A

false; this process is irreversible

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38
Q

once the sugar phosphate is attached to an NDP, what happens

A

the oxygen on the sugar phosphate serves as the nucleophile, attacking the alpha phosphate on an NTP. Leaves us with the sugar attached to NDP, and leftover PPi

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39
Q

what happens to the leftover PPi in glycogen synthesis

A

it’s quickly hydrolyzed into two phosphates

40
Q

T or F: the hydrolysis of PPi into two phosphates is exergonic

A

true

41
Q

how is glycogen synthesis initiated

A

phosphoglucomutase works in reverse: G6P –> G1P

42
Q

after G1P is formed in glycogen synthesis, what happens

A

a sugar nucleotide is formed: G1P + UTP –> UDP-glucose + PPi

43
Q

what is the reactant for glycogen synthase

A

UDP-glucose

44
Q

as the reactant for glycogen synthase, what does UDP-glucose do

A

it adds glucose to the non reducing ends of a growing glycogen chain

45
Q

T or F: glycogen synthase is able to form the a1-6 bonds at glycogen branch points

A

false; it cannot

46
Q

what is used to make the glycogen a1-6 branch points

A

a glycogen branching enzyme

47
Q

describe how the glycogen branching enzyme is used

A

it transfers a fragment of 6-7 glucose residues from the non reducing end to the C6 hydroxyl of a more interior glucose, and then glycogen synthase can extend the new branch

48
Q

what are the benefits of lots of branches of glycogen

A

branching improved the solubility, and increases the number of non reducing ends

49
Q

T or F: glycogen synthase can initiate a new glycogen polymer on its own

A

false; it cannot

50
Q

what does glycogen synthase need in order to initiate a new glycogen polymer

A

a primer

51
Q

what initiates the primer in glycogen synthesis

A

glycogenin

52
Q

what do you start with in glycogen synthesis (in regards to glycogenin)

A

UDP-glucose

53
Q

what does UDP-glucose do in glycogen synthesis

A

the glucose is donated to the OH group of Tyr of glycogenin = glucosylated Tyr

54
Q

what catalytic activity describes the formation of glucosylated Tyr

A

transferase activity (glucose transfers from UDP-glucose to the OH of Tyr)

55
Q

once Tyr is glucosylated, what happens

A

glycogenin adds seven more molecules to the original one (each derived from UDP-glucose)

56
Q

what activity describes the addition of the 7 glucose molecules onto the other one via glycogenin

A

chain extending activity

57
Q

in glycogen synthesis, once we have the 8 glucose primer, what happens

A

glycogen synthase can take over

58
Q

T or F: after the initiation of glycogen synthesis, the primer leaves

A

false; glycogenin and the primer remain in the molecule

59
Q

how many tiers does the glycogen particle have

A

12

60
Q

how many residues composes each tier of glycogen

A

12-14 residues in each tier

61
Q

how big is a glycogen molecule

A

21 nm (as big as a ribosome)

62
Q

what plays a role in the regulation of both glycogen phosphorylase and glycogen synthase

A

reversible phosphorylation

63
Q

how are the two forms of glycogen phosphorylase and glycogen synthase denoted

A

a and b forms

64
Q

describe the a form of glycogen phosphorylase and glycogen synthase

A

it’s more active

65
Q

describe the b form of glycogen phosphorylase and glycogen synthase

A

it’s less active

66
Q

describe the structure of glycogen phosphorylase

A

homodimer

67
Q

describe the a form of glycogen phosphorylase

A

phosphorylated at two serine residues

68
Q

describe the b form of glycogen phosphorylase

A

deprotonated at both serine residues

69
Q

what enzyme phosphorylates glycogen phosphorylase b to create a

A

phosphorylase b kinase

70
Q

what happens when we have the a form of glycogen phosphorylase

A

a form = active = glycogen breakdown

71
Q

what activates phosphorylase b kinase

A

glucagon; PbK gives us the active form of the enzyme which causes glycogen breakdown = glucose, so when we have glucagon (low glucose) we want the a form

72
Q

what enzyme dephosphorylated the a form into the b form

A

phosphoprotein phosphatase 1 (PP1)

73
Q

when do we want glycogen phosphorylase to be active

A

when we want glycogen breakdown

74
Q

how do we get glycogen breakdown in the muscle

A

release of adrenaline or epinephrine (ie after exercising) leads to glycogen breakdown

75
Q

how do we get glycogen breakdown in the liver

A

when we’re hungry/secreting glucagon

76
Q

name the two cell types where glycogen breakdown occurs

A

myocytes (muscle) and hepatocytes (liver)

77
Q

in glycogen breakdown in the muscle, what binds to a GPCR

A

epinephrine

78
Q

in glycogen breakdown in the liver, what binds to a GPCR

A

glucagon

79
Q

what is the name of GPCR

A

G-protein coupled receptor

80
Q

after either epinephrine or glucagon binds to the GPCR in glycogen breakdown, what happens

A

signal cascade

81
Q

what is the result of the signal cascade in glycogen breakdown

A

the cascade ensures an amplification of the signal so that a huge number of G1P molecules are freed from glycogen

82
Q

what term is used to relate the glycogen phosphorylase enzymes (one is in muscle, one in liver)

A

isozymes

83
Q

in the muscle, what activates phosphorylase b kinase to make the a form of the phosphorylase

A

Ca2+ and AMP activate it, because they signify a contracting muscle, so the a form is made which breaks down glycogen

84
Q

in the liver, what inhibits phosphorylase a activity

A

glucose

85
Q

other than inhibiting the phosphorylase a activity, what role does glucose play when it binds

A

it binding promotes a conformational change, exposing the phosphorylated Ser residues to PP1 for cleavage, giving us the inactive form

86
Q

describe how we convert to the b form of phosphorylase

A

glucose binds to the a form to inhibit it, a conformational change happens, the phosphorylated Ser residues are now exposed to PP1 for cleavage = b form (inactive)

87
Q

in glycogen synthase, which form is active; a or b

A

a is active

88
Q

in glycogen synthase, which form is phosphorylated; a or b

A

b is phosphorylated!! (tricky)

89
Q

what enzyme phosphorylated glycogen synthase to make the b form

A

glycogen synthase kinase 3 (GSK3)

90
Q

what enzyme dephosphorylated the b form of glycogen synthase to get the a form

A

phosphoprotein phosphatase 1 (PP1)

91
Q

what two molecules bind to glycogen synthase to expose the phosphates to PP1

A

glucose and G6P

92
Q

what form of glycogen synthase does insulin promote

A

a form (active)

93
Q

how does insulin promote the a form of glycogen synthase

A

it blocks GSK3 (preventing the inactive form), and it activates PP1 (to dephosphorylate the enzyme to get the active form)

94
Q

insulin binding to an insulin receptor initiates a signal cascade that activates which molecule

A

protein kinase B

95
Q

what role does protein kinase B play in glycogen synthase regulation

A

PKB phosphorylates/inactivates GSK3, leading to more glycogen synthase in the active form

96
Q

big picture: when we eat a meal, there’s high blood glucose, insulin secretion, decrease in glycogen breakdown. Describe how this happens

A

insulin inhibits GSK3 and activates PP1, fully activating glycogen synthase. Glucose enters the cell and removes hexokinase IV from the nucleus, so it enters the cytosol to make G6P which can be used for either glycolysis or glycogen synthesis.

97
Q

big picture: after a meal, there’s low blood glucose, glucagon secretion, increase in glycogen breakdown. Describe how this happens

A

protein kinase A mediates all effects of glucagon. It phosphorylated and actives phosphorylase kinase and FBPase-2. It phosphorylated and deactivates PFK2 and pyruvate kinase in the liver. Liver produces lots of G6P by glycogen breakdown and GNG, and then G6Pase makes glucose to be exported to the blood

BIOL 2421 - Cellular Biochem (21 decks)

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