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Biochemistry 441B > Carbohydrate Metabolism: Glycogen Synthesis and Degradation > Flashcards

Carbohydrate Metabolism: Glycogen Synthesis and Degradation Flashcards

1
Q

What is glycogenolysis?

A

Glycogen degredation

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2
Q

What is glycogenesis?

A

Glycogen synthesis

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3
Q

Where does glycogenolysis and glycogenesis occur?

A

Both occur in the cytosol

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4
Q

Where does glycogenolysis and glycogenesis start on the polymer?

A

Both start at the non-reducing ends of the polymer

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5
Q

What does a large number of branch-points facilitate?

A

Facilitate highly efficient mechanism to either release or rebuild glycogen particles

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6
Q

What forms a glycogen particle?

A

20-40 glycogen core complexes

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7
Q

What does core complexes consist of?

A

Glycogen protein

~50,000 Glc molecules with a-1,4 linkage in the main chain and a-1,6 branches about every 8-12 residues

creating ~2000 non-reducing ends

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8
Q

What enzymes are required for glycogenolysis?

A

Glycogen phosphorylase

Phosphoglucomutase

Glycogen debranching enzyme

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9
Q

What does glycogen phosphorylase do in glycogenolysis?

A

Catalyzes phosphorolysis of a-1,4 bonds to yield glucose-1-phosphate from the non-reducing ends

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10
Q

What does phosphoglucomutase do in glycogenolysis?

A

Converts G1P to G6P

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11
Q

What does glycogen debranching enzyme do in glycogenolysis?

A

Removes a-1,6 branches

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12
Q

Describe the steps of the use of glycogen phosphorylase.

A

Covalently binds the cofactor pyridoxal-5’-phosphate (PLP), a vitamin B6 derivative (PLP covalently linked to lysine)

Catalyzes phosphorolysis to generate the produce Glc-1-P

Processively cleaves from non-reducing ends until it is too close to an a-1,6 branch point

  • stays attached
  • goes from 1st glucose to 2nd glucose right away
  • once there are 4 sugars left, phosphorylase will stop working and will fall off as it is close to a branch point
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13
Q

AAG –> CAG

How does this mutation affect the enzyme’s activity?

A

Lysine to glutamine

Active site which can affect protein

PLP won’t bind as lysine changes and the protein will stop working

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14
Q

Describe the steps of the use of glycogen debranching enzyme.

A

Recognizes the partially degraded branch

Has dual enzymatic activity

  • Glycosyltransferase activity
  • a-1,6 Glucosidase activity
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15
Q

What does glycosyltransferase activity do?

A

Transfers 3 (of the 4 sugars) glucose units to the nearest non-reducing end

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16
Q

What does a-1,6 Glucosidase activity do?

A

Cleaves a-1,6 glycosidic bond to release free glucose

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17
Q

What is the fate of the free glucose that was cleaved by a-1,6 glucosidase activity in liver cells?

A

This glucose will be released into the blood stream

18
Q

What is the fate of the free glucose that was cleaved by a-1,6 glucosidase activity in muscle cells?

A

This glucose will go through glycolysis (use for own energy)

19
Q

Describe the steps of the use of phosphoglycomutase.

A

Converts G1P to G6P (intermediate glucose-1,6-BP)

Reaction similar to phosphoglyceratemutase except that the phosphoryl transfer group in the latter is a phosphohistidine as opposed to phosphoserine in phosphoglucomutase

Exchanging positions C1 –> C6 in the same molecule

20
Q

What does glucose-6-phosphatase convert in liver cells?

A

Converts G6P to glucose for export to the other tissues

21
Q

How is glycogen phosphorylase allosterically regulated by phosphorylation?

A

In response to hormonal signaling

  • glucagon (liver, has NO receptors on muscle cells)
  • epinephrine (liver and muscle)

Activity is stimulated by phosphorylation, which shifts the equilibrium from the T-state to the R-state

  • needs to be phosphorylated to go from T–>R
  • phosphorylated phosphorylase = active site
22
Q

How is glycogen phosphorylase allosterically regulated in muscle cells?

A

Allosterically activated by AMP

  • AMP levels high, running low in glucose
  • binding to AMP can also cause conformational changes

Allosterically inactivated by G6P and ATP

Muscle cells do not express glucagon receptors

23
Q

How is glycogen phosphorylase allosterically regulated in liver cells?

A

Glucose - a negative allosteric modulator
- if glucose is present, this will inactivate phosphorylation

Phosphorylated glycogen phosphorylase is rapidly inhibited by elevated blood glucose levels

24
Q

What enzymes are required for glycogenesis?

A

Phosphoglucomutase

UDP-glucose pyrophosphorylase

Glycogen Synthase

Glycogen Branching Enzyme

25
Q

What does Phosphoglucomutase do in glycogenesis?

A

Converts Glucose-6-phosphate to Glucose-1-phosphate

26
Q

What does UDP-glucose pyrophosphorylase do in glycogenesis?

A

Converts glucose-1-phosphate + UTP to UDP-Glucose + PPi

27
Q

What does glycogen synthase do in glycogenesis?

A

Converts UDP-Glucose + Glycogen(n) to UDP + Glycogen(n+1)

28
Q

What does glycogen branching enzyme do in glycogenesis?

A

Create a new a-1,6 branch point and a new non-reducing end

Transfers 7 Glc residues from the end of one chain to an internal point no closer than 4 Glc residues from another branch point

29
Q

What synthesis is required in glycogen synthesis?

A

Synthesis of uridine diphosphate glucose (UDP glucose)

30
Q

Why is UDP-glucose used in Glycogen Synthase?

A

Uses UDP-glucose to add glucose residues one at a time to the non-reducing ends of glycogen

31
Q

What is regenerated in Glycogen Synthase?

A

UTP (Uridine triphosphate) is regenerated from by the enzyme nucleoside diphosphate kinase, which uses ATP as a phosphoryl donor.

UTP activates sugar for glycogen synthesis

32
Q

How much ATP is used with every glucose that attaches to glycogen?

A

Every glucose that attaches to glycogen takes up 1 ATP.

33
Q

What is glycogenin?

A

Anchor protein for the glycogen core complex

Catalyzes the glycotransferase and synthesis reactions needed to generate the initial glycogen chain

34
Q

Describe the dual activity in glycogenin.

A

Glc from UDP-Glc is attached to a Tyr residue in glycogenin through an O-linked glycosidic bond that is formed via its glycosyltransferase activity
- O-linked exception as it usually attaches to Ser or Thr but here it is attached to Tyr.

A 2nd Glc is attached via its glycogen synthase activity which forms an a-1,4 glycosidic bond

35
Q

What does glycogenin build?

A

Glycogenin builds a primer

The glycogen synthase reaction is repeated 5 more times to yield an O-linked seven-residue glucose primer
- glycogenin extends chain to seven glucose residues

This in turn is used as a substrate by glycogen synthase and glycogen branching enzyme to build the glycogen core particle

36
Q

How is glycogenin used as a substrate by glycogen synthase to build the glycogen core particle?

A

Adds to glycogenin primer

37
Q

How is glycogenin used as a substrate by glycogen branching enzyme to build the glycogen core particle?

A

Adds a-1,6 linkages

38
Q

How is glycogen synthase allosterically regulated by phosphorylation?

A

Controlled by reversible phosphorylation

39
Q

How does G6P allosterically regulate Glycogen Synthase?

A

Large conformational change induced by G6P binding

Positive regulator of glycogen synthase

40
Q

Describe regulation of glycogen phosphorylase and glycogen synthase.

A

Reciprocal regulation depending on glucose concentration

As glycogen phosphorylase decreases as time after adding glycose to liver cell extracts increases, this results in glycogen synthase activity to increase (as time goes by after adding glucose to liver cell extract)

41
Q

How is glycogen metabolism hormonal regulated?

A

Insulin activates glycogen synthase and inactivates glycogen phosphorylase

Glucagon activates glycogen phosphorylase and inactivates glycogen synthase

42
Q

What is Lysosomal a-1,4-glucosidase?

A

Disease name: Pompe

Organs affected: all organs

Heart failure in infantile form, muscle defects in juvenile form

Biochemistry 441B (10 decks)

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