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Biochem > Glycogen Degradation > Flashcards

Glycogen Degradation Flashcards

1
Q

Occurs when?

Where?

What happens?

A

FASTED state

Liver

Break down stored glycogen

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2
Q

Catabolic hormones (2)

A

Glucagon and epinephrine

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3
Q

Focus in fasted state is how body maintains :

A
  1. Glucose homeostasis

2. Energy homeostasis

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4
Q

Ways to maintain glucose homeostasis

A
  1. Glycogen degradation

2. Gluconeogenesis

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5
Q

During fasted state, what happens to glucose ?

A

All glucose is preserved for uses by brain and RBC

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6
Q

Ways to maintain energy homeostasis

A
  1. Fatty acid oxidation

2. Ketogenesis

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7
Q

Importance of fatty acids in fasted state

A

FATTY ACIDS are ALTERNATIVE FUEL source in FASTED STATE

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8
Q

After about _____ hours after eating, glucose oxidation drops.

What do you do?

A

4 hours

  • Begin to breakdown stored glycogen
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9
Q

Glycogen degradation peaks at about ____ hours without food

A

12

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10
Q

Glycogen does not last much beyond _____ hours

A

24

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11
Q

What happens along with glycogen degradation?

A

Gluconeogenesis

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12
Q

After about ___ days of fasting, gluconeogenesis declines.

Why / significance?

A

3 days

Fatty acids are so high in blood —> liver takes them up and oxidizes into ketone bodies which can be used as alternative energy source for glucose
Also, skeletal muscle (protein breakdown) is spared

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13
Q

Ketone bodies

Function?

A
  • Glucose and protein sparing

Used as an alternative energy source for glucose when fasting.
- Oxidized in mitochondria

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14
Q

Ketone bodies can be used by ?

Cannot be used by?

A

Can be used by all tissues (even brain)

Cannot be used by RBC b/c no mitochondria to oxidize them

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15
Q

Conditions for degrading glycogen in muscle (3)

A
  1. During exercise
  2. Stress
  3. Elevated epinephrine
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16
Q

Receptors on muscle cells

A

NO glucagon receptors

Epinephrine receptors ONLY

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17
Q

Conditions that trigger glycogen degradation in liver

A
  1. Overnight fast (low I/G)

2. To some extent, epinephrine

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18
Q

Liver receptors

A

Glucagon AND epinephrine

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19
Q

Major enzyme in glycogen degradation

A

Glycogen phosphorylase

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20
Q

Glycogen phosphorylase attacks _____________

A

Alpha-1,4-glycosidic bonds

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21
Q

Glucose cleavage occurs at?

A

Non-reducing ends with a free -OH at C4

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22
Q

How is glucose rapidly released?

A

Multiple molecules of glucose can be released at once because multiple molecules of glycogen phosphorylase can be working away on same glycogen molecule starting at different branches

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23
Q

Type of reaction

A

Phosphorolysis

24
Q

Glucose is released as _________

Advantage:

A

Glucose-1-phosphate

Advantage = do not need to use ATP

25
Q

How to get glucose from the product of glycogen degradation?

A

G-1-P isomerizes to G-6-P —> cleave off phosphate

26
Q

Phosphate donor

A

Phosphoric acid (HPO4 2-)

  • Intracellular buffer so readily available
  • Phosphate ion acts as nucleophile to split alpha-1,4-glycosidic bonds
27
Q

Process of glycogen degradation

(4) enzymes

A
  1. Glycogen phosphorylase cleaves alpha-1,4-glycosidic bonds by adding a phosphate to yield G-1-P
  2. Transferase moves 4 residues closest to branch point to end of another branch because glycogen phosphorylase is sterically hindered
  3. Alpha-1,6-glucosidase cleaves branch point
  4. Phosphoglucomutase catalyzes isomerization of G-1-P —> G-6-P
28
Q

Chemistry of phosphoglucomutase reaction

A

Enzyme has active site serine with phosphate on it —> Enzyme transfer its phosphate onto C-6 —> form glucose-1,6-bisphosphate —> enzyme removes phosphate from C-1 and puts it back on serine —> form glucose-6-phosphate

29
Q

Fate of glucose-6-phosphate in liver

A

Glucose-6-phosphatase removes P to yield glucose (so transporter recognizes it)

Glucose goes into blood to maintain blood glucose homeostasis

30
Q

Fate of glucose-6-phosphate in muscle

A

Stays in muscle

Enters glycolysis to provide ATP

31
Q

Muscle cannot be used to maintain blood glucose homeostasis because (2)

A
  1. No glucagon receptors

2. Lacks glucose-6-phosphatase

32
Q

Major regulated enzyme in glycogen degradation

A

Glycogen phosphorylase

33
Q

___________ and ___________ are reversely regulated

A

Glycogen synthase and glycogen phosphorylase

34
Q

In fasted state, glycogen synthase is __________ and ____________ by

A

Phosphorylated and inactivated

By glycogen synthase kinase

35
Q

In fasted state, glycogen phosphorylase is ________ and _______ by

A

Phosphorylated and ACTIVE

Glucagon (or epi) activate PKA through cAMP which phosphorylates phosphorylase kinase which phosphorylates glycogen phosphorylase making it active

36
Q

Liver condition of interest =

A

Fasted state

37
Q

Muscle condition of interest =

A

Endurance exercise or stress

38
Q

Increase glycogen degradation IN LIVER in response to:

A

Low I/G

Or epinephrine

39
Q

Increase glycogen degradation IN MUSCLE in response to:

A

Epinephrine

40
Q

Glycogen phosphorylase has ?

A

2 interconvertible forms: Phosphorylase a and Phosphorylase b

*each form can in the T state or R state

41
Q

Phosphorylase b vs. Phosphorylase a

A

Phosphorylase a : always phosphorylated, more active form

Phosphorylase b : dephosphorylated, inactive form

42
Q

What does phosphorylase a do?

Where?

A

In BOTH liver and muscle, phosphorylase a degrades glycogen.

43
Q

In response to hormonal signaling in fasted state…

A

Phosphorylase kinase uses ATP as substrate to add phosphate group onto phosphorylase b to convert it to phosphorylase a form —>

Phosphorylase a degrades glycogen.

44
Q

Predominant form in muscle

A

Phosphorylase b in T state

45
Q

In muscle ________ is only converted to _______ with ___________.

A

Phosphorylase b is only converted to phosphorylase a with epinephrine signaling.

46
Q

When muscle begins contraction —>

A

ATP levels drop —> energy charge is low so have high AMP —> AMP binds allosterically to T state of phosphorylase b —> converts it to R state

47
Q

Phosphorylase b in R state

A

More active but NOT phosphorylated

48
Q

Muscle:

Binding _____ to phosphorylase ___ in the ___ state converts it to the _______ ____ state.

A

Binding AMP to phosphorylase b in the T state converts it to the active R state.

49
Q

Significance of AMP allosteric regulation in muscle

A

Allows glycogen degradation to begin before hormonal control (epi) can activate phosphorylase b to phosphorylase a

Allows contraction to continue without being starved for glucose

50
Q

What connects glycolysis and glycogen degradation in muscle?

A

AMP

Muscle is contracting so energy charge is low.

51
Q

Glucose from glycogen degradation _______________

A

Stays in muscle and goes through glycolysis to produce ATP

52
Q

Result of AMP function in muscle

A
  1. AMP activates muscle phosphorylase b to begin degrading glycogen before it is actually phosphorylated
  2. AMP simultaneously stimulates glycolysis so as soon as glucose is released by glycogen degradation, it is immediately put in glycolysis pathway to alter energy change and make ATP
53
Q

Predominant form in liver

A

Phosphorylase a in R state

54
Q

In fed state, insulin signaling activates ___________ to ____________

A

PP1 to remove phosphate from phosphorylase a converting it to phosphorylase b, inactivating it.

55
Q

As soon as blood glucose levels rise —> ______ state is converted to _____ state

A

R state is converted to T state

56
Q

T state of phosphorylase a in liver

A

Less active but still phosphorylated

57
Q

Significance of blood glucose control in liver

A

Converting phosphorylase R state to T state slows down breakdown of glycogen when the liver cells sense an increase in glucose concentration before insulin cascade can take effect

Biochem (15 decks)

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