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BC Metabolism > Lecture 2: Glycogen Metabolism > Flashcards

Lecture 2: Glycogen Metabolism Flashcards

1
Q

Which three amino acids a) can be phosphorylated and b) are most commonly phosphorylated in metabolic proteins?

A

a) Serine, Threonine and Tyrosine

b) Serine and Threonine

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2
Q

Give the general names for the types of enzymes which a) add a phosphate group and b) remove a phosphate group.

A

a) protein kinase

b) phosphoprotein phosphatase

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3
Q

In what type of cells are hormones made?

A

Endocrine cells

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4
Q

How are hormones transported around the body?

A

Bloodstream

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5
Q

How can the addition or removal of a phosphate group activate/deactivate an enzyme?

A

The addition/removal of a phosphate group causes a conformational change, which causes a change in the shape of the active site, thus affecting its affinity for the substrate (activating/deactivating it).

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6
Q

What is the American name for adrenaline?

A

Epinephrine

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7
Q

Where is adrenaline stored?

A

Adrenal glands above the kidneys

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8
Q

Where is insulin made?

A

Pancreas

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9
Q

Where is glycagon made?

A

Pancreas

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10
Q

When is insulin released?

A

When blood glucose levels are high

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11
Q

When is glycagon released?

A

When blood glucose levels are low

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12
Q

Which overrides the other: signals within the cell or hormonal signals?

A

Hormonal signals

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13
Q

Is phosphorylated pyruvate kinase more or less active than the non-phosphorylated enzyme?

A

Less active

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14
Q

What happens in the liver when blood glucose is low? (focus on glycolysis)

A

When blood sugar is low:

  • glucagon hormone is released into bloodstream
  • glucagon stimulates cyclic AMP-dependent protein kinase (PKA)
  • PKA catalyses the phosphorylation of pyruvate kinase using ATP and releasing ADP
  • Pyruvate kinase is now in its less active form
  • Glycolysis slows and less glucose is used up
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15
Q

Which enzymes in the TCA cycle are regulated by ADP and ATP levels?

A

Pyruvate dehydrogenase, citrate synthase and isocitrate.

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16
Q

Which enzymes in the TCA cycle are regulated by Succinyl-CoA?

A

Alpha-ketoglutarate and citrate synthase

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17
Q

Which enzymes in the TCA are regulated by NADH?

A

Pyruvate dehydrogenase, citrate synthase and alpha-ketoglutarate.

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18
Q

Other than ATP and NADH, what is citrate synthase inhibited by?

A

Succinyl CoA and Citrate (the product of its reaction)

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19
Q

What is pyruvate dehydrogenase activated/inhibited by?

A

Pyruvate dehydrogenase is activated by AMP, CoA and NAD+ and inhibited by ATP, Acetyl CoA, NADH and fatty acids.

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20
Q

What are the monomers in glycogen?

A

Glucose

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21
Q

What is an anomeric carbon?

A

A carbon which can have 2 conformations, e.g. alpha or beta.

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22
Q

What are the linkages in glycogen?

A

Predominantly alpha-1,4 linkages, with alpha-1,6 brances

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23
Q

What is found in the centre of a glycogen granule?

A

A protein called glycogenin

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24
Q

Where is glycogen found in the cell?

A

In the cytoplasm

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25
Q

Why must glycogen granules be insoluble?

A

If glycogen were soluble, a huge osmotic pressure would build up.

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26
Q

Which organisms have glycogen?

A

Animals and some fungi

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27
Q

Is it easy or difficult for glucose to be mobilised from glycogen?

A

Easy

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28
Q

If excess energy can be stored as fat, why do we need glycogen?

A

Some tissues can’t degrade fat (fatty acids), including the brain, which needs glucose. This is because fatty acids cannot pass the blood-brain barrier, but glucose can.

Also, red blood cells need glucose, because they have no mitochondria, where fatty acids are broken down.

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29
Q

The degradation of which macromolecule is responsible for the majority of ATP produced?

A

Fatty acids, which enter the TCA cycle via Acetyl CoA after undergoing beta oxidation.

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30
Q

Where in the body is glycogen stored?

A

In the liver and muscles

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31
Q

Why is glycogen stored in the muscles?

A

Glycogen is available in the muscles to provide ATP when muscles contract rapidly

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32
Q

Why is glycogen stored in the liver?

A

If glucose levels are low, the liver breaks down glycogen, releasing glucose (especially for the brain)

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33
Q

What is the name of the main enzyme responsible for glycogen synthesis?

A

Glycogen synthase

34
Q

Other than enzymes, what is needed for glycogen synthesis?

A

UDP-glucose (nucleotide (uracil here) sugar donor)

35
Q

Describe the linkage and position of glucose sugars added to glycogen by glycogen synthase.

A

Glycogen synthase adds glucose sugars to the non-reducing end of the glycogen molecule using an alpha-1,4 linkage.

36
Q

Why is it useful for glycogen to be so heavily branched?

A

Glycogen synthase only adds glucose to the ends of strands of glycogen, so it is useful for glycogen to be heavily branched so that there are many ends available. This means that excess glucose can be added very quickly to glycogen.

37
Q

Name the enzymes involved in synthesising UDP-Glucose, in the order that they appear in the pathway.

A

Hexokinase, Phosphoglucomutase and UDP-Glucose pyrophosphorylase

38
Q

What is the first step in the synthesis of UDP-Glucose? Name the enzyme which catalyses this step.

A

Glucose + ATP —–> Glucose-6-phosphate + ADP

Hexokinase

39
Q

What is the second step in the synthesis of UDP-Glucose? Name the enzyme which catalyses this step.

A

Glucose-6-phosphate –> Glucose-1-phosphate

Phosphoglucomutase

40
Q

What is the third step in the synthesis of UDP-Glucose? Name the enzyme which catalyses this step.

A

Glucose-1-phosphate + UTP —–> UDP-Glucose + PPi

UDP-Glucose pyrophosphorylase

41
Q

What is the other name for the glycogen branching enzyme?

A

Glycosyl-4,6-transferase

42
Q

Where is the glycogen chain does branching occur?

A

6 to 7 glucose residues from the non-reducing end

43
Q

How many residues must the glycogen branch have in total?

A

Eleven

44
Q

Which linkage is used to create a branch in the glycogen?

A

Alpha-1,6 linkage

45
Q

Can glycogen synthase initiate glycogen synthesis?

A

No, glycogen synthase needs a chain with at least 8 glucose residues.

46
Q

What initiates glycogen synthesis?

A

Glycogenin, the enzyme in the centre of glycogen

47
Q

What are the two enzyme activities of glycogenin?

A

Glucosyltransferase activity and chain extending activity

48
Q

Describe what happens in the first stage of glycogen synthesis initiation.

A

Glycogenin catalyses the addition of glucose from UDP-glucose onto tyrosine (which is attached to the glycogenin), with the release of UDP. (The hydrogen on the tyrosine is lost and the lone pair of electrons on the oxygen of tyrosine nucleophilically attack the carbon 1 on the glucose in UDP-glucose).

49
Q

Describe what happens in the chain extending stage of glycogen synthesis initiation.

A

The lone pair of electrons of the oxygen on the carbon 4 of the growing glycogen chain nucleophilically attacks the carbon 1 in the UDP-Glucose. The glycogenin’s chain extending activity allows this addition to happen 7 times, producing [Glucose]8-O-Glycogenin.

50
Q

Name the main enzyme responsible for glycogen breakdown.

A

Glycogen phosphorylase

51
Q

What type of cleavage does glycogen phosphorylase use? Explain what this entails.

A

Phospholytic cleavage. This involves storing the energy of the glycosidic bond which is broken by forming a phosphoester.

52
Q

What is used as a cofactor in glycogen breakdown and what is this molecule derived from?

A

Pyridoxial phosphate, which is derived from vitamin B6.

53
Q

How many residues away from an alpha-1,6 linkage can a glycogen phosphorylase no longer break off glucose?

A

4

54
Q

What is released when glycogen phosphorylase cleaves an alpha-1,4 linkage in glycogen?

A

Glucose-1-phosphate

55
Q

How is the problem of glycogen phosphorylase not cleaving right up to the alpha-1,6 linked glucose solved?

A

The debranching enzyme uses its transferase activity to move the 3 remaining glucose residues to the non-reducing end of another branch.

56
Q

What is the second activity of the debranching enzyme?

A

alpha-1,6 glucosidase activity
The debranching enzyme removes the branching alpha-1,6 linked glucose residue via a simple hydrolysis reaction, releasing free glucose (no phosphate involved)

57
Q

What is the ratio of Glucose-1-phosphate:Glucose released in glycogen breakdown?

A

10:1

58
Q

What reaction does the Glucose-1-phosphate released during glycogen breakdown undergo? Name the enzyme.

A

Glucose-1-phosphate –> Glucose-6-phosphate

Phosphoglucomutase

59
Q

Which amino acid in the active site of phosphoglucomutase is important in the conversion of glucose-1-phosphate to glucose-6-phosphate?

A

Serine

60
Q

Describe how phosphoglucomutase catalyses the conversion of glucose-1-phosphate to glucose-6-phosphate.

A

The serine in the active site of phosphoglucomutase gives a phosphate group to glucose-1-phosphate, putting it on the carbon 6, producing Glucose-1,6-bisphosphate as an intermediate. The serine (now with -OH instead of -O-P) takes the phosphate group from the carbon 1 of the two-phosphate intermediate, regenerating the original Ser-O-P at the phosphoglucomutase active site and producing glucose-6-phosphate.

61
Q

What happens to glucose-6-phosphate in the muscles?

A

It is used in glycolysis to produce ATP for muscle contraction.

62
Q

What happens to glucose-6-phosphate in the liver?

A

The glucose-6-phosphate is transported into the ER, where the enzyme glucose-6-phosphatase removes the phosphate, releasing free glucose into the cytoplasm.

63
Q

Which is the more active form: phosphorylase a or phosphorylase b?

A

Phosphorylase a is the more active form.

64
Q

Which part of the enzyme glycogen phosphorylase b is phosphorylated to give phosphorylase a?

A

Two serine residues (Ser 14)

65
Q

Which enzyme catalyzes the reaction phosphorylase b + 2 ATP –> phosphorylase a + 2 ADP?

A

phosphorylase b kinase

66
Q

Which reactions does phosphoprotein phosphatase 1 catalyse?

A
  • phosphorylase a + 2 H2O –> phosphorylase b (inactive) + 2 Pi
  • phosphorylated pyruvate kinase –> non-phosphorylated pyruvate kinase (active)
  • glycogen synthase b —> glycogen synthase a (active)
67
Q

Which hormones stimulate the phosphorylation of phosphorylase b to phosphorylase a and why?

A

Glucagon and adrenaline. Glucagon is released into the blood when blood glucose levels are too low, so it activates glycogen phosphorylase so that it breaks down glycogen, producing more glucose.

Adrenaline is released into the blood in times of stress, when more energy may be required (fight or flight). Thus, adrenaline activates glycogen phosphorylase so that is breaks down glycogen, producing more glucose for ATP production.

68
Q

Which hormone inhibits the phosphorylation of phosphorylase b to phosphorylase a and why?

A

Insulin, which is produced when blood glucose levels are high. This inhibits the activation of glycogen phosphorylase so that glycogen is not broken down to glucose unnecessarily.

69
Q

What is phosphorylase a inhibited by in the liver and why?

A

Glucose, because when glucose levels are high, it is unnecessary for the liver to break down glycogen and release glucose into the bloodstream.

70
Q

What is phosphorylase b activated/inhibited by in the muscle and why?

A

Inhibited by: Glucose-6-phosphate (glycolysis is going slowly, so more glucose is not needed) and ATP (high ATP levels in the muscles means extra glucose is not needed for more ATP production)

Activated by: AMP (when AMP levels are high, ATP levels are low, so glycogen needs to be broken down to produce more glucose for ATP production)

71
Q

How are glycogen phosphorylase and glycogen synthase regulated?

A

Phosphorylation

72
Q

Which of glycogen synthase b and glycogen synthase a is a) the more active form and b) the phosphorylated form?

A

a) glycogen synthase a

b) glycogen synthase b

73
Q

Give the main enzyme which catalyses the dephosphorylation of glycogen synthase?

A

Phosphoprotein phosphatase (PP1)

74
Q

Give the final enzyme which phosphorylates glycogen synthase?

A

Glycogen synthase kinase (GSK3)

75
Q

Which hormone regulates the phosphorylation of glycogen synthase and why?

A

Insulin, which inactivates glycogen synthase kinase (GSK3), thus preventing phosphorylation (and deactivation) of glycogen synthase b to glycogen synthase a.
If insulin is in the bloodstream, blood glucose is high, so glucose –> glycogen is necessary in the muscles/liver to store the excess glucose as glycogen.

Insulin also activates phosphoprotein phosphatase 1 (PP1), which catalyses the activation of glycogen synthase b to a.

76
Q

Give the allosteric activators/inhibitors of glycogen synthase in the liver.

A

Glucose-6-phosphate is an allosteric activator of glycogen synthase. It binds to the b forms and enhances the phosphorylation by phosphoprotein phosphatase (PP1) to glycogen synthase a (more active form). If there is an accumulation of Glucose-6-P, then glycolysis is going slowly, so there is an excess of glucose, so glucose should be stored as glycogen.

77
Q

Which organ(s) are affected by a) glucagon, b) adrenaline and c) insulin? (With respect to glycogen)

A

a) liver (stimulates the release of glucose from glycogen to supply (esp.) the brain, red blood cells and rapidly contracting muscles
b) muscles (prepare for high consumption of energy)
c) liver and muscles (stimulates storage of excess glucose)

78
Q

What happens in the liver when blood glucose is low? (focus on glycogen)

A

Glucagon is released into the bloodstream and binds to a transmembrane receptor in the liver. A G-protein then releases GTP (from GDP), which causes adenylate cyclase (another transmembrane protein) to convert ATP into cycle AMP (cAMP), which in turn causes protein kinase A to be converted to its activated form (phosphorylated). The activated protein kinase A then catalyses two reactions: glycogen synthase a (active) –> glycogen synthase b (inactive) (glycogen is no longer synthesised from glucose, so blood glucose levels do not fall further) and inactive phosphorylase b kinase –> active phosphorylase b kinase. The active phosphorylase b kinase then phosphorylates glycogen phosphorylase b (less active) to glycogen phosphorylase a (more active), which catalyses the breakdown of glycogen to glucose-1-P. Glucose-1-P is then converted to glucose-6-P by phosphoglucomutase. Thus, blood glucose levels rise again as glycogen breakdown is increased.

79
Q

What happens in the liver when blood glucose is low?

A

Glucagon is released into the bloodstream and causes cyclic AMP to be released, activating cAMP-dependent protein kinase. This protein kinase causes glycolysis in the liver to slow down, so that blood glucose levels do not fall further. cAMP-dependent protein kinase also causes glycogen in the liver to be broken down into glucose-1-phosphate and eventually glucose, and glycogen synthesis to slow.

80
Q

What happens in the liver/muscle when blood glucose is high?

A

Insulin is released into the bloodstream and binds to insulin receptors in the membrane of liver/muscle cells, causing an -OH group on the receptor to be replaced with a phosphate group. This triggers the activation of many protein kinases, which catalyse the deactivation of active glycogen synthase kinase to inactive glycogen synthase kinase. This prevents glycogen synthase from being inactivated by active glycogen synthase kinase. Existing inactive glycogen synthase b is activated by phosphoprotein phosphatase (PP1). This results in high rates of glycogen synthesis from glucose and blood glucose levels fall.

81
Q

Give three enzymes which are targeted by Phosphoprotein phosphatase (PP1) and the result in the interaction.

A
  • PP1 dephosphorylates glycogen synthase, making it more active
  • PP1 dephosphorylates glycogen phosphorylase kinase, making it less active and unable to phosphorylate glycogen phosphorylase b.
  • PP1 dephosphorylates glycogen phosphorylase a, making it less active.
82
Q

Give a brief summary of how the hormones involved control glycogen synthesis and breakdown.

A

Glucagon/Adrenaline –> phosphorylation of glycogen phosphorylase b –> more active –> increased glycogen breakdown
Insulin –> dephosphorylation of glycogen phosphorylase b –> less active –> decreased glycogen breakdown

Glucagon/Adrenaline –> phosphorylation of glycogen synthase –> less active –> decreased glycogen synthesis
Insulin –> dephosphorylation of glycogen synthase –> more active –> increased glycogen synthesis

BC Metabolism (9 decks)

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