Breakdown of Cellular glycogen Flashcards
Where does breakdown of cellular glycogen take place?
liver, particularly in the cytosol of cells
Glycogen has 2 linkages, which are?
α(1→4) and α(1→6) linkages with branching every 10-12 subunits
How many steps are there and what are these?
4 Steps:
1. Glycogenolysis/Phosphorolysis
2. Debranching
3. G1P to G6P
4. G6P to glucose in liver for blood supply
In step 1, what enzyme is present, substrate, product, and if allosteric inhibitors/activators can act with enzyme?
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
Is step 1 regulated? How?
Yes via phosphorylation and dephosphorylation
What prohibits further removal of glucose units from glycogen?
if glucose unit is 4 or 5 subunits from branch due to size or cleft
How does glycogen bind to its enzyme in step 1?
enzyme has specific 30nm-crevice for binding of non-reducing end of glycogen which can accommodate 4-5 glucose units
Step 1 catalysis involves the coenzyme pyridoxal phosphate. How does the substrate get converted to its product?
glycogen and phosphate enter the active site, forming an oxonium ion intermediate, forming G1P
In the debranching step (step 2), what is the limit branch?
4-5 glucose units from α(1→6) linkage
In step 2, what enzyme is present, substrate, product, and if allosteric inhibitors/activators can act with enzyme?
glycogen debranching enzyme, glycogen to glucose which phosphorylizes to G6P, no allosteric inhibitors/activators.
Mechanism of step 2?
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
In step 3, what enzyme is present, substrate, product, and if allosteric inhibitors/activators can act with enzyme?
phosphoglucomutase, G6P to G1P, no allosteric inhibitors/activators
Mechanism of step 3?
phospho-Ser give Pi to C6 of glucose, and C1 of glucose gives back Pi to Ser residue regenerating phospho-Ser
What is the fate of G6P in the liver?
G6P does not typically proceed to glycolysis especially if blood glucose is low. However, liver still uses G6P in glycolysis for energy
Where does G6P go if not in glycolysis?
Goes to lumen of ER
What happens when G6P is embedded in the ER?
- removes phosphate group yielding glucose
- glucose transporters exit the cell and carried to other cells via bloodstream
Glucose phosphorylase (GP) in the liver is usually in what form?
Active phosphorylase A form, deactivated (shift to T-state) by glucose
Glucose phosphorylase (GP) in the muscle is usually in what form?
inactive phosphorylase B form activated when AMP is present due to consummation of ATP (when muscle is active)
What catalyzes phosphorylation of GP?
Phosphorylase kinase (PK) partly activated by binding Ca2+ to PK
How is Ca2+ released?
Muscle contractions
Protein Kinas eA phosphorylates PK to what form?
fully active form
