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Metabolism > 3. Glycogen metabolism > Flashcards

3. Glycogen metabolism Flashcards

1
Q

what does glycogen phosphorylase mechanism require?

A

pyridoxal phosphate cofactor covalently bonded

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2
Q

G6p can enter 4 pathways:

A

Converted back to glucose (happens a lot in liver)

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3
Q

__________ __________ needs to be maintained, so not eating for a while, can result in breakdown of glycogen and formation of glucose

A

blood glucose

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4
Q

Difference between starch and glycogen

A

Very frequent branching in glycogen

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5
Q

4 reasons to not use fat or glucose itself as storage:

A

1 - fast catabolism via glycolysis as quick conversion to glucose (fat takes forever)

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6
Q

if we have to store emergency nutrient, why cant we store ATP?

A

ATP increases osmolarity! Just like glucose!!!

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7
Q

2 advantages of extensive branching for glycogen:

A

1 - multiple non reducing end to provide multiple sites to produce gluc simultaneous

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8
Q

So that multiple glycogen phosphorylases can act at several non-reducing ends of glycogen chains to generate large amount of Glucose-1-P for glycolysis, or to release glucose in blood very quickly. True or false?

A

TRUE

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9
Q

Why are non reducing ends so important?

A

Glycogen breakdown reactions start from the Non-reducing end of the chain

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10
Q

True or false?

A

TRUE

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11
Q

3 major enzymes in glycogen breakdown:

A
  1. glycogen phophorylase
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12
Q

What does glycogen phosphorylase do:

A

the most important enzyme for regulation, attacks the non reducing end and chops 1 by 1 glucose out of glycogen AND adds phosphate to it to form G1P (breaks 1-4 linkage)

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13
Q

What does glycogen debranching enzyme do:

A

breaks 1-6 linkage that made the branch

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14
Q

What does phosphoglucomutase do:

A

convert G1P to the useful G6P

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15
Q

atp net gain is ___ if from glycogen because already phosphorylated glucose without atp use.

A

3

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16
Q

_____________ is used to convert g1p to glucose.

A

phosphatase

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17
Q

Allosteric inhibitors and activators of glycogen phosphorylase:

A

inhibitors: atp, g6p, and glucose

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18
Q

What is required for glycogen phosphorylase to function?

A

Pyridoxal phosphate (PLP) cofactor covalently bounded

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19
Q

Describe the structure of glycogen phosphorylase:

A

Dimer of 2 identical subunits. Each subunit has an Amino terminal domain. Each domain includes an interface subdomain (phosphorylation and allosteric site) and a glycogen binding subdomain (glycogen storage site)

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20
Q

Describe the mechanism of glycogen phosphorylase reaction:

A

1.Oxygen in ring forms double bond, causing the a(1-4) linkage to separate while Pi loses a proton to glycogen chain and PLP loses a proton to Pi –> Half-chair oxonium ion intermediate

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21
Q

What type of substitution is the glycogen phosphorylase mechanism including and what is the evidence?

A

SN1

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22
Q

Conformation stays same after glyc phosphorylase rxn. True or false?

A

TRUE

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23
Q

What are the 2 steps of the SN1 mechanism?

A
  1. Formation of oxonium ion
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24
Q

What enzyme acts on the product of glycogen phosphorylase? Explain:

A

Phosphoglucomutase acts on G1P to form G6P.

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25
Q

Describe the Phosphoglucomutase mechanism:

A

Enzyme has a phosphorylated serine residue. This phosphate is added to form G1,6BP. The C-1 phosphate is given back to the serine to form G6P

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26
Q

What happens to G6P after the phosphoglucomutase reaction?

A

G6p in the liver is reacted upon by another enzyme –> G6Pase –> glucose is free and secreted into the bloodstream to maintain blood glucose

27
Q

What is the third enzyme involved in glycogen breakdown? Describe its two functions:

A

Glycogen debranching enzyme.

28
Q

Approximately ___% of the total glucose residues generated from glycogen breakdown are as free glucose and ___% as G1P.

A

10

29
Q

Glycogen synthesis is achieved by three enzymes. Name and briefly mention the function of each one:

A

I. UDP-glucose phosphorylase –> adds UDP to glucose

30
Q

What 2 enzymes must be critically controlled for proper regulation of glycogen metabolism?

A

1.Glycogen phosphorylase

31
Q

The enzymatic activities of Glycogen phosphorylase and glycogen synthase are controlled by two ways;

A

I.By direct allosteric control

32
Q

3 ways to regulate enzymes:

A
  1. control substrate and product concentrations
33
Q

Describe allosteric control of glycogen phosphorylase:

A

G6P and ATP are allosteric inhibitors of Glycogen phosphorylase whereas AMP is an allosteric activator.

34
Q

G6P is an allosteric activator of glycogen synthase. True or false?

A

TRUE

35
Q

Describe covalent modification (phosphorylation) control of glycogen phosphorylase

A

If hungry or in emergency situation, hormones are released (epinephrine and glucagon) to active phosphorylase kinase to activate inactive glycogen phosphorylase into the super-active glycogen phosphorylase “a”.

36
Q

Phosphorylase ‘a’ (phosphorylated form) is more active than phosphorylase ‘b’ (dephosphorylated form.) True or false?

A

TRUE

37
Q

Is allosterics able to regulate phosphorylase a?

A

No, if u have a lot of glucose (0.5M), phosphorylase a can be deactived, but this can only happen in vitro… physiologically, phosphorylase a is so active that it cannot be deactivated by atp,g6p.

38
Q

How is glycogen phosphorylase phosphorylation regulated?

A

PKA activates phosphorylase kinase, which phosphorylates glycogen phosphorylase to form active “a” form. Once emergency situation is over, phosphoprotein phosphatase chops up “a” active (removes phosphate).

39
Q

How is PKA regulated?

A

4 cAMP molecules bind to the 2 regulatory subunits of the enzyme, detaching the 2 catalytic units, which becomes free to phosphorylate phosphorylase kinase

40
Q

Describe the formation of cAMP:

A

ATP is converted to cAMP by adenylyl cyclase

41
Q

Describe the breakdown of cAMP and why it would happen:

A

Cyclic nucleotide phosphodiesterase breaks down cAMP to AMP

42
Q

How are caffeine and theophylline involved?

A

They block Cyclic nucleotide phosphodiesterase, meaning you remain active instead of having cAMP go back to AMP.

43
Q

List the steps to Epinephrine-dependent activation of cAMP production by adenylate cyclase:

A
  1. Epinephrine binds to its specific receptor.
44
Q

What is the advantage of multi-step processes?

A

amplification!

45
Q

Describe the function of phosphoprotein phosphatase 1 (PP1c)

A

PP1c is the enzyme, shuts down glycogen phosphorylase by taking phosphate (no more glycogen degradation) –> we do this when full

46
Q

Describe the upregulation of phosphoprotein phosphatase 1 (PP1c) and when it would occur:

A

When full and blood glucose is high = insulin is secreted = activated insulin-stimulated protein kinase = phosphorylated upper-side of Gm subunit of PP1c = active PP1c = cleaves glycogen phosphorylase, phosphorylase kinase, and glycogen synthase, resulting in decreased phosphorylation and leading to increased glycogen synthesis

47
Q

Describe the downregulation of phosphoprotein phosphatase 1 (PP1c) and when it would occur:

A

In emergency situation/hunger, epinephrine secreted = pathway produces PKA = phosphorylation of phosphorylase kinase and the bottom-end of Gm subunit of PP1 = active phosphorylase kinase and inactive PP1c = glycogen breakdown increased

48
Q

What happens if you receive both up and downregulation signals for PP1c (insulin bc well-fed and epinephrine bc a tiger is chasing you)?

A

Once the bottom-site is phosphorylated (inactive), the phosphatase is inactivated EVEN IF the top-site is phosphorylated (active site)

49
Q

PKA and cAMP both result in inhibition of PP1, and so both are in favour of glycogen breakdown. True or false?

A

TRUE

50
Q

How is glycogen synthase different from glycogen phosphorylase?

A

Active when dephosphorylated, whereas glycogen phosphorylase is active when phosphorylated

51
Q

Describe glycogen synthase regulation:

A
  • PKA, phosphorylase kinase, and other kinases phosphorylate glycogen synthase –> INACTIVE
52
Q

Pathway to form cyclic AMP

A

glucagon

53
Q

_________ receptor produces a signal to release _________ , which is needed for activation of phosphorylase kinase

A

beta

54
Q

Action of glucagon in liver and muscle cells:

A

Muscle:

55
Q

Action of Epinephrine on liver and muscle cells:

A

Liver:

56
Q

Action of insulin on liver and muscle cells:

A

Liver:

57
Q

List the steps to increasing low blood glucose levels:

A
  • Low blood glucose
58
Q

List the steps to decreasing high blood glucose levels:

A
  • High blood glucose
59
Q

Defects in glycogen liver enzymes generally cause what 2 symptoms and in muscle enzymes generally what symptom?

A
  • hepatomegaly and hypoglycemia
60
Q

Name and describe type I hereditary glycogen storage disease. Include treatment.

A

von Gierke’s disease: G6Pase deficiency

61
Q

Name and describe type VI hereditary glycogen storage disease. Include treatment.

A

Liver phosphorylase deficiency (Her’s Disease): Patients unable to use liver glycogen. Symptoms and treatments are similar to type I disease.

62
Q

Name and describe type IV hereditary glycogen storage disease. Include treatment.

A

Branching enzyme deficiency (Anderson’s Disease): Presence of unbrached long chains of glycogen, which become insoluble particles, causing sever liver malfunction. The abnormal size particle may trigger immune response that causes liver damage and death of the patients within 4 yr of age.

63
Q

Name and describe type 0 hereditary glycogen storage disease. Include treatment.

A

Type 0: Liver glycogen synthase deficiency: This is the only disease of glycogen metabolism where there is deficiency of glycogen. Hyperglycemia after the meals and hypoglycemia in other times.

64
Q

Name and describe type V hereditary glycogen storage disease. Include treatment.

A

Type V: Muscle phosphorylase deficiency (McArdle’s Disease): symptoms appear in adulthood with severe muscle cramps after strenuous exercise. Blood glucose remain unaffected (because liver phosphorylase is unaffected)

Metabolism (14 decks)

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