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M1 > Glycogen Metabolism > Flashcards

Glycogen Metabolism Flashcards

1
Q

A readily-mobilizable storage of glucose

A

Glycogen

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2
Q

Two places in the body glycogen is found

A
  • liver (10% glycogen by weight): acts as “buffer” to maintain blood glucose levels
  • muscle (1-2%): source of fuel for quick, sudden, strenuous activity
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3
Q

Glycogen is present in granules called _______

A

“Beta particles” >55,000 residues; 21 nm in diameter Contain enzymes that degrade, synthesize and regulate glycogen

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4
Q

Glycogen is a large branched polymer of _______

A

glucose

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5
Q

glucose residues are connected by

A

alpha-1,4 o-glycosidic bonds with alpha-1,6 branch points every ~10 residues

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6
Q

How many non-reducing ends per Beta-particle is in glycogen

A

>20,000

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7
Q

Glycogen has _____ reducing end(s) – it is attached to the protein _______

A

one; glycogenin

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8
Q

Amount of glycogen in liver _______ between meals and in early stages of starvation. It _______immediately after meals.

A

decreases; increases

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9
Q

Breakdown of glycogen involves 4 enzymatic activities:

A
  1. Release of glucose 1-phosphate (from NR ends): glycogen phosphorylase
  2. Remodeling to remove branchpoints: debranching enzyme (two activities)
    1. glucosidase
    2. transferase
  3. Conversion of Glu1P to Glu6P: phosphoglucomutase
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10
Q

Glycogen synthesis involves

A
  • Glycogen synthase: uses UDP-glucose as substrate
  • Branching enzyme: creates alpha-1,6 branchpoints
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11
Q

Glycogen breakdown and synthesis are _______ regulated

A

reciprocally

different enzymes, different substrates/products

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12
Q

Glycogen phosphorylase cannot approach any closer than ____ residues from a branch point

A

4

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13
Q

Glycogenolysis debranching enzyme

A

Transferase: shifts block of 3 glucose units

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14
Q

Hydrolyzes branch point, generating glucose (Converted to Glu6P via hexokinase) in glycogenolysis

A

Alpha-1,6-glucosidase

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15
Q

The fourth activity of glycogenolysis

A

phosphoglucomutase

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16
Q

Carries out phosphorolysis (cleavage of a bond using orthophosphate, Pi)

A

Glycogen Phosphorylase

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17
Q

Glycogen phosphorylase is energetically _______; because the product is _______

A

favorable; already phosphorylated

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18
Q

Glu1P, being charged, remains ______ and is used for energy; ______, Glu1P converted to glucose and secreted

A

remains inside muscle cell; in liver

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19
Q

Despite Delta G0 being ~ zero, inside the cell equilibrium lies far to right due to

A

mass action effects

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20
Q

Glycogen phosphorylase requires _______ as a cofactor

A

pyridoxal phosphate (PLP)

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21
Q

muscle and liver isozymes are regulated (same/differently)

A

differently

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22
Q

Glycogenolysis: Phosphoglucomutase

A
  • An isomerase: intramolecular group transfer
  • Active site contains phosphoserine residue
  • Reaction proceeds via intermediate, Glu-1,6-bisP
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23
Q

Muscle glycogen phosphorylase activity is highly regulated both ________ and by __________

A

allosterically (“b”-form) and by reversible covalent modification (phosphorylation)

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24
Q

Allosteric inhibitors of muscle glycogen phosphorylase activity

A

ATP Glu6P

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25
Q

Activator of muscle glycogen phosphorylase activity

A

AMP

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26
Q

Phosphorylation is under _______ control

A

hormonal

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27
Q

Enzyme of muscle glycogen phosphorylase regulation is a _______ of two ____ kDa subunits; _____ active sites

A

homodimer; 97; two

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28
Q

GPPase ___: phosphorylated, usually active, in _____

A

“a” ; R-state

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29
Q

GPPase ____: unphosphorylated, usually inactive, in _____.

A

“b”; T-state

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30
Q

True or false: both “a: and “b” forms can exist in both states

A

True

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31
Q

GPPase “b” converted to “a” via ________, _______, on each subunit

A

phosphorylation of single serine residue, serine-14

32
Q

In muscle GPPase “b” is ususally ______, because levels of allosteric inhibitors is usually _____

A

inactive; high

33
Q

GPPase “b” is only active when level of _____ is high, e.g., during vigorous exercise

A

AMP

34
Q

GPPase “b” is responsive to _______

A

energy charge

35
Q

hormone epinephrine can convert ____ to ____

A

“b” to “a”

36
Q

GPPase ___ nearly always on or active

A

“a”

37
Q

In the liver the default state is ______ which is allosterically inhibited by ______ and is insensitive to _____

A

“a” (active) form; glucose (acts as a glucose sensor); AMP

38
Q

Phosphorylase b kinase has the composition

A

(abgd)4 (alphabetagammadelta)4

39
Q

In muscle phosphorylase b kinase is activated by either

A

phosphorylation (by PKA) or Ca2+

binding fully activated when both involved

40
Q

____levels rise in muscle cell during muscle contraction

A

Ca2+

41
Q

Phosphorylation site is on

A

Beta subunit

42
Q

Ca2+ binds to ______

A

delta subunit (also known as calmodulin)

43
Q

In glycogenesis (glycogen synthesis) UDP-glucose is the substrate for ______

A

glycogen synthase

44
Q

Glycogen synthase catalyzes formation of new ________

A

alpha-1,4 glycosidic linkages

45
Q

Glycogen synthesis requires the protein _______

A

Glycogenin (G)

46
Q

Glycogenin acts as both an _____ and an _____

A

initial primer; enzyme

47
Q

Glycogenin first: _______ Next:

A
  • transfers glucose from UDP-glucose to hydroxyl of tyrosine (Tyr-194) on protein
  • extends chain by addition of 7 more residues
48
Q

catalyzes the formation of a-1,6 glycosidic linkages in glycogen by transferring a block of about 7 residues to a more interior location.

A

branching enzyme New branchpoint must be at least 4 residues from preexisting one

49
Q

Branching does what?

A

Increases the solubility of glycogen and facilitates both its synthesis and its degradation

50
Q

Addition of one glucose residue to glycogen uses

A

two ATP equivalents

Hexokinase: ATP –> ADP [UDP-glucose pyrophosphorylase + glycogen synthase]: UTP –> UDP

51
Q

How would you expect low blood glucose level to affect glycogenesis? glycogenolysis?

A

Low blood glucose level, through the action of glucagon (liver) or epinephrine (liver, muscle) inhibits glycogenesis and stimulates glycogenolysis.

52
Q

How would you expect high blood glucose level to affect glycogenesis? glycogenolysis?

A

High blood glucose level, through the action of insulin, stimulates glycogenesis and inhibits glycogenolysis in liver and muscle.

53
Q

In liver, insulin activates Glycogen Synthase by inactivating

A

Glycogen Synthase Kinase-3

54
Q

major regulatory enzyme of glycogenesis

A

glycogen synthase

55
Q

In the liver glycogen synthase exists in two states:

A
  1. active, “a” (unphosphorylated) and inactive
  2. “b” (phosphorylated)
56
Q

(Liver) glycogen synthase Can be phosphorylated on various serine residues by >11 different kinases, including ____

A

GSK3 Action of GSK3 opposed by PP1 and insulin

57
Q

IRS-1

A

insulin receptor substrate-1

58
Q

PIP2 and PIP3

A

phosphatidylinosito 4,5-bisphosphate and 3,4,5-trisphosphate, respectively

59
Q

PDK-1

A

phosphoinositide-dependent kinase-1

60
Q

PKB

A

proteine kinase B (also known as Akt)

61
Q

PP1 is tightly bound to

A

glycogen-targeting protein (GM)

62
Q

glycogen targeting protein (GM) forms a complex with the 3 enzymes:

A
  1. GS
  2. GPPase
  3. Phosphorylase kinase on glycogen granule
63
Q

PP1 becomes activated when: PP1 unbinds and becomes inhibited when:

A
  • GM is singly phosphorylated (by ISK)
  • A second phosphorylation of GM (by PKA) occurs
64
Q

High glucose levels activate

A

glycogenesis

65
Q

Binding of glucose to GPase-a causes :

A

an R-to-T shift and PP1-mediated dephosphorylation.

66
Q

This frees PPI to dephosphorylate GS

A

GPase-b being released

67
Q

The sequential mechanism of full GPase inactivation prior to GS activation insures that

A

a futile cycle does not occur

68
Q

glycogen synthase b is allosterically activated by

A

Glu6P

69
Q

Epinephrine triggered signaling cascade

A
70
Q

Fates of Glucose-6-Phosphate

A
71
Q
A

Glycogen Phosphorylase

72
Q

Glycogen Storage Diseases

A
73
Q

Hormal Control of Glycogen Metabolism After a Meal or at Rest

A
74
Q

Hormal Control of Glycogen Metabolism during Exercise of Fasting

A
75
Q
A

Phosphoglucomutase

M1 (48 decks)

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