Breakdown of Cellular glycogen

Question 1

Where does breakdown of cellular glycogen take place?

Answer 1

liver, particularly in the cytosol of cells

Question 2

Glycogen has 2 linkages, which are?

Answer 2

α(1→4) and α(1→6) linkages with branching every 10-12 subunits

Question 3

How many steps are there and what are these?

Answer 3

4 Steps:
1. Glycogenolysis/Phosphorolysis
2. Debranching
3. G1P to G6P
4. G6P to glucose in liver for blood supply

Question 4

In step 1, what enzyme is present, substrate, product, and if allosteric inhibitors/activators can act with enzyme?

Answer 4

glycogen phosphorylase. glycogen to glucose via removal of glucose subunits,
inhibitors: ATP, G6P, and glucose shifts to T-state
activator: AMP shifts to R-state

Question 5

Is step 1 regulated? How?

Answer 5

Yes via phosphorylation and dephosphorylation

Question 6

What prohibits further removal of glucose units from glycogen?

Answer 6

if glucose unit is 4 or 5 subunits from branch due to size or cleft

Question 7

How does glycogen bind to its enzyme in step 1?

Answer 7

enzyme has specific 30nm-crevice for binding of non-reducing end of glycogen which can accommodate 4-5 glucose units

Question 8

Step 1 catalysis involves the coenzyme pyridoxal phosphate. How does the substrate get converted to its product?

Answer 8

glycogen and phosphate enter the active site, forming an oxonium ion intermediate, forming G1P

Question 9

In the debranching step (step 2), what is the limit branch?

Answer 9

4-5 glucose units from α(1→6) linkage

Question 10

In step 2, what enzyme is present, substrate, product, and if allosteric inhibitors/activators can act with enzyme?

Answer 10

glycogen debranching enzyme, glycogen to glucose which phosphorylizes to G6P, no allosteric inhibitors/activators.

Question 11

Mechanism of step 2?

Answer 11

enzyme has domain for transferase activity and hydrolase activity. Glucan transferase (GT) cuts 3-4 residues which attach to the non-reducing end which glycogen phosphorylases again. Glycosidase (GC), for hydrolase activity, hydrolyzes α(1→6) bonds releasing glucose

Question 12

In step 3, what enzyme is present, substrate, product, and if allosteric inhibitors/activators can act with enzyme?

Answer 12

phosphoglucomutase, G6P to G1P, no allosteric inhibitors/activators

Question 13

Mechanism of step 3?

Answer 13

phospho-Ser give Pi to C6 of glucose, and C1 of glucose gives back Pi to Ser residue regenerating phospho-Ser

Question 14

What is the fate of G6P in the liver?

Answer 14

G6P does not typically proceed to glycolysis especially if blood glucose is low. However, liver still uses G6P in glycolysis for energy

Question 15

Where does G6P go if not in glycolysis?

Answer 15

Goes to lumen of ER

Question 16

What happens when G6P is embedded in the ER?

Answer 16

1. removes phosphate group yielding glucose
2. glucose transporters exit the cell and carried to other cells via bloodstream

Question 17

Glucose phosphorylase (GP) in the liver is usually in what form?

Answer 17

Active phosphorylase A form, deactivated (shift to T-state) by glucose

Question 18

Glucose phosphorylase (GP) in the muscle is usually in what form?

Answer 18

inactive phosphorylase B form activated when AMP is present due to consummation of ATP (when muscle is active)

Question 19

What catalyzes phosphorylation of GP?

Answer 19

Phosphorylase kinase (PK) partly activated by binding Ca2+ to PK

Question 20

How is Ca2+ released?

Answer 20

Muscle contractions

Question 21

Protein Kinas eA phosphorylates PK to what form?

Answer 21

fully active form