Carbohydrate Metabolism: Glycogen Synthesis and Degradation

Question 1

What is glycogenolysis?

Answer 1

Glycogen degredation

Question 2

What is glycogenesis?

Answer 2

Glycogen synthesis

Question 3

Where does glycogenolysis and glycogenesis occur?

Answer 3

Both occur in the cytosol

Question 4

Where does glycogenolysis and glycogenesis start on the polymer?

Answer 4

Both start at the non-reducing ends of the polymer

Question 5

What does a large number of branch-points facilitate?

Answer 5

Facilitate highly efficient mechanism to either release or rebuild glycogen particles

Question 6

What forms a glycogen particle?

Answer 6

20-40 glycogen core complexes

Question 7

What does core complexes consist of?

Answer 7

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

Question 8

What enzymes are required for glycogenolysis?

Answer 8

Glycogen phosphorylase

Phosphoglucomutase

Glycogen debranching enzyme

Question 9

What does glycogen phosphorylase do in glycogenolysis?

Answer 9

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

Question 10

What does phosphoglucomutase do in glycogenolysis?

Answer 10

Converts G1P to G6P

Question 11

What does glycogen debranching enzyme do in glycogenolysis?

Answer 11

Removes a-1,6 branches

Question 12

Describe the steps of the use of glycogen phosphorylase.

Answer 12

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

Question 13

AAG –> CAG

How does this mutation affect the enzyme’s activity?

Answer 13

Lysine to glutamine

Active site which can affect protein

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

Question 14

Describe the steps of the use of glycogen debranching enzyme.

Answer 14

Recognizes the partially degraded branch

Has dual enzymatic activity

• Glycosyltransferase activity
• a-1,6 Glucosidase activity

Question 15

What does glycosyltransferase activity do?

Answer 15

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

Question 16

What does a-1,6 Glucosidase activity do?

Answer 16

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

Question 17

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

Answer 17

This glucose will be released into the blood stream

Question 18

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

Answer 18

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

Question 19

Describe the steps of the use of phosphoglycomutase.

Answer 19

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

Question 20

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

Answer 20

Converts G6P to glucose for export to the other tissues

Question 21

How is glycogen phosphorylase allosterically regulated by phosphorylation?

Answer 21

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

Question 22

How is glycogen phosphorylase allosterically regulated in muscle cells?

Answer 22

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

Question 23

How is glycogen phosphorylase allosterically regulated in liver cells?

Answer 23

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

Phosphorylated glycogen phosphorylase is rapidly inhibited by elevated blood glucose levels

Question 24

What enzymes are required for glycogenesis?

Answer 24

Phosphoglucomutase

UDP-glucose pyrophosphorylase

Glycogen Synthase

Glycogen Branching Enzyme

Question 25

What does Phosphoglucomutase do in glycogenesis?

Answer 25

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

Question 26

What does UDP-glucose pyrophosphorylase do in glycogenesis?

Answer 26

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

Question 27

What does glycogen synthase do in glycogenesis?

Answer 27

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

Question 28

What does glycogen branching enzyme do in glycogenesis?

Answer 28

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

Question 29

What synthesis is required in glycogen synthesis?

Answer 29

Synthesis of uridine diphosphate glucose (UDP glucose)

Question 30

Why is UDP-glucose used in Glycogen Synthase?

Answer 30

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

Question 31

What is regenerated in Glycogen Synthase?

Answer 31

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

Question 32

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

Answer 32

Every glucose that attaches to glycogen takes up 1 ATP.

Question 33

What is glycogenin?

Answer 33

Anchor protein for the glycogen core complex Catalyzes the glycotransferase and synthesis reactions needed to generate the initial glycogen chain

Question 34

Describe the dual activity in glycogenin.

Answer 34

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

Question 35

What does glycogenin build?

Answer 35

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

Question 36

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

Answer 36

Adds to glycogenin primer

Question 37

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

Answer 37

Adds a-1,6 linkages

Question 38

How is glycogen synthase allosterically regulated by phosphorylation?

Answer 38

Controlled by reversible phosphorylation

Question 39

How does G6P allosterically regulate Glycogen Synthase?

Answer 39

Large conformational change induced by G6P binding Positive regulator of glycogen synthase

Question 40

Describe regulation of glycogen phosphorylase and glycogen synthase.

Answer 40

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)

Question 41

How is glycogen metabolism hormonal regulated?

Answer 41

Insulin activates glycogen synthase and inactivates glycogen phosphorylase Glucagon activates glycogen phosphorylase and inactivates glycogen synthase

Question 42

What is Lysosomal a-1,4-glucosidase?

Answer 42

Disease name: Pompe Organs affected: all organs Heart failure in infantile form, muscle defects in juvenile form