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Biochem 1 > Glycogen Metabolism > Flashcards

Glycogen Metabolism Flashcards

1
Q

Glycogen and epinephrine have ____ effects on glycogen synthase activity

A

negative

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2
Q

Role of glycogen in muscle/most tissues

A

storage form of glucose that ultimately is used to generate ATP inside cell

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3
Q

Role of glycogen in liver

A

Breaks down glycogen and serves as a source of glucose for other tissues by Glucose 6 phosphatase

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4
Q

How does glycogen stores change in the liver from well-fed to starvation

A

Well fed state - high

24 h starvation - low because it have been breaking down to release glucose

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5
Q

What is the structure of gluycogen

A
  • It is the storage form of glucose in animal cells.
  • It is a polymer of glucose containing a-1,4 glyosidic bonds and a-1,6 bonds at branch points
  • Glycogen allows large amounts of glucose to be stored in the cell because of branch points
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6
Q

How is Glycogen synthesized?

A
  • When glucose is taken up into a liver cell, its converted to G-6-P which is converted to G-1-P
  • G-1-P is converted to UDP-glucose which is the immediate donor of glucose residues to glycogen
  • The degradation products of glycogen are G-1-P and glucose
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7
Q

How is Glycogen degraded?

A
  • In degradation, glycogen is broken down to G-1-P and glucose
    G-1-P can be converted to G-6-P since the liver has G-6-Pase, the phosphate is removed and glucose can leave
  • In muscle cell, the G-6-P is not dephosphorylated, but will enter glycolysis
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8
Q

What is glycogenesis

A
  • synthesis of glycogen from glucose
  • Initial steps involve a protein, glycogenin (which is a primer and an enzyme)
  • Glycogenin catalyzes the transfer of glucose residues from UDP glucose and keeps adding on UDP-glucose residues to form a glycogen primer

after that glycogen synthase will add on to the primer and branching enzyme will make branches

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9
Q

How does UDP-glucose acts as glucose donor for glycogen

A
  • The negatively charged phosphate in G-1-P attacks the alpha-phosphate of UTP
  • Pyrophosphate (PPi) is displaced
  • Hydrolysis of PPi drives the reaction forward
  • The high energy bond in UDP-glucose favors incorporation of glucose to glycogen
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10
Q

Explain the process of glycogen synthesis

A

Glycogen synthase elongates an already existing glycogen chain which was made my glocogenin

  • the substrate for glycogen synthase are glycogen and UDP-glucose
  • glucose from UDP-glucose is transferred from the non-reducing end of glycogen chain
  • the glycogen chain is increased by 1 glucose with a new a-1,4-glycosidic linkage by glycogen synthase
  • the synthase adds glucose residues until the chain reaches a certain length
  • glycogen synthase can’t form the a-1,6 glycosidic linages
  • the branching enzyme cleaves a 6-9 unit of glucosyl residues and forms an a-1,6-glycosidic bond with a glucosyl residue in the glycogen core
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11
Q

What is the rate limiting step in glycogen synthesis

A

glycogen synthase

UDP-glucose –> UDP

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12
Q

How is glycogenesis regulated?

A

glycogen synthase catalyzes the rate limiting step

  • glucagon (liver) and epinephrine (liver and muscle) have negative effects on glycogen synthase activity
  • insulin causes an increase in glycogen synthase activity
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13
Q

Which is the active and inactive form of glycogen synthase?

A

Inactive - phosphorylated

active - no phosphate group (de-phosphorylation)

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14
Q

Glucagon/epinephrine favour the _____ form of glycogen synthase

A

inactive

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15
Q

Insulin favors the ____ form of glycogen synthase

A

active

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16
Q

How is glycogen synthase phosphorylated?

A

The phosphorylation is initiated by cAMP-depended protein kinase A

17
Q

What is glycogenolysis?

A

The breakdown of glycogen into glucose

18
Q

What is glycogen degraded to?

What happens to the product?

A

Glycogen is degraded into glucose 1-P and glucose

Glucose-1-P is converted to glucose-6-P for entry into other pathways

19
Q

How is glycogen degraded?

A

By 2 enzymes:

  1. Glycogen phosphorylase - - breaks the a-1,4-glycosidic bonds by using a phosphate ion as a nucleophile and releasing G-1-P
    - if water was used to break the bond, we would get glucose which would leave the cell. With phosphate, the phosphate is kept and cant leave the cell
    - Glycogen phosphorylase cannot degrade glucosyl residues near the branch point
  2. The debrancher enzyme
    - transferase activity - removes the glucosyl residues and adds it to a longer chain through a-1,4, glycosidic bond
    - a-1,6-glucosidase activity - hydrolyzes the a,1-6-glycosidic bond to release glucose by adding water
20
Q

Which enzyme catalyzes the rate limited step in glycogen-degradation?

A

Glycogen phosphorylase

21
Q

What is the major and minor product of glycogen degradation?

A

major - Glucose-1-phosphate

minor - glucose

22
Q

The degradation of glycogen normally produces which of the following?

A. More glucose than glucose-1-phosphate
B. More glucose-1-phosphate than glucose
C. Equal amounts of glucose and glucose-1-phosphate
D. Only glucose-1-phosphate
E. Only glucose
A

B. More glucose-1-phosphate than glucose

23
Q

How is glycogenolysis regulated?

A
  • Glycogen phosphorylase catalyzes the rate-limiting step.
  • Glucagon (liver) and epinephrine (liver and muscle) have positive effects on glycogen phosphorylase activity
  • Insulin causes a decrease in glycogen phosphorylase activity
24
Q

How is glycogen metabolism regulated in the liver in the fed state

A
  • we have insulin present
  • it will activate glycogen synthase
  • inhibit glycogen phosphorylase
25
Q

How is glycogen metabolism regulated in the liver in the fasting state

A
  • We have glucagon present
  • inhibits glycogen synthase
  • activates glycogen phosphorylase
26
Q

The role of liver glycogenolysis

A
  • Glucagon and epinephrine increases cAMP
  • cAMP activates PKA
  • PKA activates glycogen phosphorylase
  • PKA also inactivates glycogen synthase
  • It reciprocally controls glycogen degradation - will have increase in breakdown of glycogen and release of glucose from cell/increased glucose output
27
Q

How is metabolism regulated in the muscle in the fed state

A
  • we have insulin here
  • promotes glycogen synthesis
  • activates glycogen synthase
  • inhibits glycogen phosphorylase
28
Q

How is metabolism regulated in the muscle in the fasting state

A

We have epinephrine

  • Will inhibit glycogen synthase
  • Activates glycogen phosphorylase
  • Ca2+ is released which activates glycogen phosphorylase
  • AMP activates glycogen phosphorylase
29
Q

Stimulation of muscle glycogenolysis by epinephrine

A
  • Epinephrine has GPCR in muscle cell. It increases cAMP
  • cAMP activates PKA
  • PKA activates glycogen phosphorylase
  • PKA inhibits glycogen synthase
  • end result is to produce G-6-P which can be used glycolysis
30
Q

Activation of Muscle glycogenolysis and glycolysis by AMP

A
  • High AMP is a sign that energy status of the cell is low = Low ATP/ADP
  • ATP levels don’t change too much
  • AMP levels change
    _ When muscles contract, AMP goes up. This is a sign to the cell that it needs more energy
  • AMP activates PFK-1 - committed step of glycolysis
  • AMP activates glycogen phosphorylase - rate limited step in glycogenolysis
31
Q

Activation of muscle glycogen phosphorylase during exercise

A
  • AMP activates glycogen phosphorylase
  • Ca2+-calmodulin activates phosphorylate kinase
  • Epinephrine activates PKA
  • PKA activates phosphorylase kinase
  • Phosphorylase kinase activates glycogen phosphorylase
32
Q 
Glycogen storage diseases: Von Gierke Disease. 
Which enzyme is defective?
Which organ is affected?
How is Glycogen in the organ affected?
Clinical features?
A
  • Glucose 6-phosphatase (glucose can’t leave cell and G-6-P, starting material for glycogen synthesis, will build up)
  • Liver and kidney
  • Increased amount
  • Massive enlargement of liver, severe hypoglycemia (because glucose can’t leave cell), ketosis (build of ketone bodies), hyperlipemia
33
Q 
Glycogen storage diseases: 
McArdie
Which enzyme is defective?
Which organ is affected?
How is Glycogen in the organ affected?
Clinical features?
A
  • Glycogen phosphorylase (rate limiting step in breaking down glycogen)
  • Muscle
  • Moderately increased
  • Limited ability to perform strenuous exercise because of painful muscle cramps (we need ATP to release myosin from muscle, so wo ATP, there will be painful muscle cramps), dont build up lactate (product of anaerobic respiration/glyccolysis, bc dont have glucose for glycolysis)
34
Q

Concerning glycogen metabolism, which of the following statement is false?

A. Insulin stimulates glycogen formation.
B. The process of glycogen breakdown is not the reverse of glycogen synthesis
C. Glycogen synthase can synthesize both a-1,4 and a-1,6 glycosidic linkages.
D. In the liver, glycogen breakdown occurs in the fasting state.

A

C. Glycogen synthase can synthesize both a-1,4 and a-1,6 glycosidic linkages.

35
Q

Why is glycogen levels not influenced by fasting state in muscle cells?

A

There is no receptor for glucagon on muscle cells.

36
Q

What affects glycogen levels in the muscle?

A

Exercise

stress

Biochem 1 (22 decks)

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