Glycogen Metabolism Wk3

Question 1

Glycogen is a

Answer 1

Carbohydrate storage molecule
Reservoir of glucose units

Question 2

Where is glycogen stored?

Answer 2

Mainly in muscle and liver

Question 3

Structure of glycogen

Answer 3

Branched glucose polymer
Units joined by α (1-4) links
Branches have α (1-6) links
All links are glycosidic bonds

Question 4

Glycogenesis = glycogen synthesis

Answer 4

Glycogen(n) + glucose-1-phosphate + UTP —> Glycogen(n+1) + UDP + 2P i

Question 5

UDP-glucose pyrophosphorylase

Answer 5

UDP-glucose is formed from glucose-1-phosphate and uridine triphosphate (UTP)

UDP-glucose is an activated compound that donates glucose residues to a growing chain

As glucose residuals are added to glycogen, UDP - glucose is the substrate and UDP is released as a reaction product

Question 6

Glycogen synthase catalyses the elongation…

Answer 6

Of glycogen chains
Transfers the glucose moiety of UDP-glucose to the C4 hydroxyl at the terminal residue of a glycogen chain to form an α(1,4) glycosidic linkage

Question 7

NB Glycogen synthase cannot link two glucose residues together

Question 8

Glycogenin protein dimer initiates glycogen synthesis

Answer 8

Glycogenin catalyses attachment of a glucose residue from UDP-glucose to one of its own tyrosine residues (Tyr194), releasing UDP as a product
followed by glucosylation at C4 of the attached glucose
product is an O-linked disaccharide with an α(1,4) glycosidic linkage
process is repeated until a short linear glucose polymer with α(1,4) glycosidic linkages is built up

		= the glycogen primer

Question 9

Glycogenin reaction

Question 10

Glycogen branching enzyme

Answer 10

Amylo-(1,4—>1,6)transglycosylase

Question 11

Amylo-(1,41,6)transglycosylase breaks α(1,4) linkage between glucose residues in glycogen chain

Answer 11

Donor chain least 11 residues long
Transfers 7-residue segment from end of glycogen chain to C6 hydroxyl of glucose residue of the same or different glycogen chain.
Yields branch with α(1,6) linkage

Question 12

Putting in branches

Answer 12

O. O Growing chain α(1,4) linked residues O.O O
O O. Branching enzyme O O. O
OO OOO\ α(1,6) linkage
O\ α(1,6) linkage O
O O

Question 13

Net result of synthetic process is a spherical mol with a protein core of glycogenin surrounded by a branched network of glucose residues

Question 14

Structure of glycogen

Answer 14

Every branch has non-reducing end
Glycogen dismantled from end of each branch at same time
Site of attack = rapid release of glucose when needed

Question 15

Glylogenolysis = glycogen breakdown

Answer 15

Glycogen breaks down to glucose-g-phosphate

Question 16

Enzymes involved in glycogen breakdown g..p d.. e p..

Answer 16

Glycogen phosphorylase
Debranching enzyme
Phosphoglucomutase

Question 17

Glycogen phosphorylase

Answer 17

thermodynamically reversible (ΔG0’ = +3.1 kJ.mol-1)
High [Pi] in cytosol drives degradation
Glucose residue removed from non-reducing end of branch
Phosphorolysis reaction, so glucose-1-phosphate released
Due to its size, enzyme can only work at least 4 residues from a branch point

Question 18

Glycogen debranching enzyme

Answer 18

Removes branches to allow further glucose residues to be available to glycogen phosphorylase
Two independent active sites, transferase and α(1,6)glucosidase
Transferase transfers three glucose residue from a 4-residue limit branch to the end of another branch, diminishing the limit branch to a single glucose residue
Glucosidase catalyses hydrolysis of the α(1,6) linkage, yielding free glucose

Question 19

Reactions catalysed by debranching enzyme

Question 20

Phosphoglucomutase

Answer 20

Fates of the glucose-6-phosphate (G6P) product:

Muscle: G6P enters glycolysis to provide energy for muscle function

Liver: G6P may be dephosphorylated for release into the blood to restore blood glucose levels

Question 21

Liver smooth ER

Question 22

Diseases of glycogen metabolism

Answer 22

11 glycogen storage disease
Most enzymes of glycogen metabolism can be affected
Symptoms :
None
Muscle cramps/ excercise intolerance
Failure to thrive / death
Incidence approx 1 in 25,000 to 40,000

Question 23

Mc Ardle’s disease
Type V glycogen storage disease
Lack of skeletal muscle isoform of glycogen phosphorylase

Answer 23

Symptoms
Muscle weakness
Muscle cell damage during exercise → myoglobin in plasma/urine → kidney damage
Test?
CK in plasma (which isoenzyme?)
Muscle biopsy (high glycogen, low phosphorylase activity)
Genetic (85% have R50X mutation)

Question 24

Von Gierke’s disease
Type 1 glycogen storage disease
Lack of enzyme glucose -6-phosphatase (G6Pase)
Mutations in G6P or Pi transporters in ER membrane

Answer 24

Symptoms
Primary issue is fasting hypoglycaemia
Test
EM on liver biopsy
Test G6Pase activity

Question 25

Conclusion

Answer 25

2 distinct pathways for glycogen synthesis and breakdown
Deficiencies in enzymes cause glycogen storage diseases