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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
Activator of muscle glycogen phosphorylase activity
AMP
26
Phosphorylation is under _______ control
hormonal
27
Enzyme of muscle glycogen phosphorylase regulation is a _______ of two ____ kDa subunits; _____ active sites
homodimer; 97; two
28
GPPase \_\_\_: phosphorylated, usually active, in \_\_\_\_\_
"a" ; R-state
29
GPPase \_\_\_\_: unphosphorylated, usually inactive, in \_\_\_\_\_.
"b"; T-state
30
True or false: both "a: and "b" forms can exist in both states
True
31
GPPase “b” converted to “a” via \_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_, on each subunit
phosphorylation of single serine residue, serine-14
32
In muscle GPPase "b" is ususally \_\_\_\_\_\_, because levels of allosteric inhibitors is usually \_\_\_\_\_
inactive; high
33
GPPase "b" is only active when level of _____ is high, e.g., during vigorous exercise
AMP
34
GPPase "b" is responsive to \_\_\_\_\_\_\_
energy charge
35
hormone epinephrine can convert ____ to \_\_\_\_
"b" to "a"
36
GPPase ___ nearly always on or active
"a"
37
In the liver the default state is ______ which is allosterically inhibited by ______ and is insensitive to \_\_\_\_\_
"a" (active) form; glucose (acts as a glucose sensor); AMP
38
Phosphorylase b kinase has the composition
(abgd)4 (alphabetagammadelta)4
39
In muscle phosphorylase b kinase is activated by either
phosphorylation (by PKA) or Ca2+ binding fully activated when both involved
40
\_\_\_\_levels rise in muscle cell during muscle contraction
Ca2+
41
Phosphorylation site is on
Beta subunit
42
Ca2+ binds to \_\_\_\_\_\_
delta subunit (also known as calmodulin)
43
In glycogenesis (glycogen synthesis) UDP-glucose is the substrate for \_\_\_\_\_\_
glycogen synthase
44
Glycogen synthase catalyzes formation of new \_\_\_\_\_\_\_\_
alpha-1,4 glycosidic linkages
45
Glycogen synthesis requires the protein \_\_\_\_\_\_\_
Glycogenin (G)
46
Glycogenin acts as both an _____ and an \_\_\_\_\_
initial primer; enzyme
47
Glycogenin first: _______ Next:
* transfers glucose from UDP-glucose to hydroxyl of tyrosine (Tyr-194) on protein * extends chain by addition of 7 more residues
48
catalyzes the formation of a-1,6 glycosidic linkages in glycogen by transferring a block of about 7 residues to a more interior location.
branching enzyme New branchpoint must be at least 4 residues from preexisting one
49
Branching does what?
Increases the solubility of glycogen and facilitates both its synthesis and its degradation
50
Addition of one glucose residue to glycogen uses
two ATP equivalents Hexokinase: ATP --\> ADP [UDP-glucose pyrophosphorylase + glycogen synthase]: UTP --\> UDP
51
How would you expect low blood glucose level to affect glycogenesis? glycogenolysis?
Low blood glucose level, through the action of glucagon (liver) or epinephrine (liver, muscle) inhibits glycogenesis and stimulates glycogenolysis.
52
How would you expect high blood glucose level to affect glycogenesis? glycogenolysis?
High blood glucose level, through the action of insulin, stimulates glycogenesis and inhibits glycogenolysis in liver and muscle.
53
In liver, insulin activates Glycogen Synthase by inactivating
Glycogen Synthase Kinase-3
54
major regulatory enzyme of glycogenesis
glycogen synthase
55
In the liver glycogen synthase exists in two states:
1. active, “a” (unphosphorylated) and inactive 2. “b” (phosphorylated)
56
(Liver) glycogen synthase Can be phosphorylated on various serine residues by \>11 different kinases, including \_\_\_\_
GSK3 Action of GSK3 opposed by PP1 and insulin
57
IRS-1
insulin receptor substrate-1
58
PIP2 and PIP3
phosphatidylinosito 4,5-bisphosphate and 3,4,5-trisphosphate, respectively
59
PDK-1
phosphoinositide-dependent kinase-1
60
PKB
proteine kinase B (also known as Akt)
61
PP1 is tightly bound to
glycogen-targeting protein (GM)
62
glycogen targeting protein (GM) forms a complex with the 3 enzymes:
1. GS 2. GPPase 3. Phosphorylase kinase on glycogen granule
63
PP1 becomes activated when: PP1 unbinds and becomes inhibited when:
* GM is singly phosphorylated (by ISK) * A second phosphorylation of GM (by PKA) occurs
64
High glucose levels activate
glycogenesis
65
Binding of glucose to GPase-a causes :
an R-to-T shift and PP1-mediated dephosphorylation.
66
This frees PPI to dephosphorylate GS
GPase-b being released
67
The sequential mechanism of full GPase inactivation prior to GS activation insures that
a futile cycle does not occur
68
glycogen synthase b is allosterically activated by
Glu6P
69
Epinephrine triggered signaling cascade
70
Fates of Glucose-6-Phosphate
71
Glycogen Phosphorylase
72
Glycogen Storage Diseases
73
Hormal Control of Glycogen Metabolism After a Meal or at Rest
74
Hormal Control of Glycogen Metabolism during Exercise of Fasting
75
Phosphoglucomutase

M1 (48 decks)

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