Glycogen Metabolism - Glycogen Breakdown Flashcards
(31 cards)
What are the two major storage tissues for glycogen?
Liver and muscle
In muscles, what does the need for ATP result in?
The conversion of glycogen to glucose-6-phosphate (G6P) for entry into glycolysis
In the liver, what is triggered when blood glucose concentration is low?
Glycogen breakdown to G6P, which gets hydrolyzed to glucose and released into the bloodstream to reverse this situation
What enzymes are required for glycogen breakdown?
1) Glycogen phosphorylase
2) Glycogen debranching enzyme
3) Phosphoglucomutase
What does glycogen phosphorylase catalyze and yied?
Catalyzes glycogen phosphorolysis (bond cleavage by the substitution of a phosphate group) to yield glucose-1-phospate (G1P)
What does glycogen debranching enzyme remove, permit, and hydrolyze?
- Removes glycogen’s branches, thereby permitting the glycogen phosphorylase reaction to go to completion
- Hydrolyzes alpha(1–>6) linked glycosyl units to yield glucose
*92% of glycogen’s glucose residues are converted to G1P and the remaining 8% at the branch points are converted to glucose
What does phosphoglucomutase convert?
G1P to G6P which can either continue along the glycolytic pathway (as in muscle) or be hydrolyzed to glucose (as in liver)
What is glycogen phosphorylase regulated by?
Both allosteric interactions and by covalent modification
What is glycogen phosphorylase a dimer of?
Identical 842-residue subunits that catalyze the controlling step in glycogen breakdown
Glycogen phosphorylase is involved in an enzyme-catalyzed modification/demodification process to yield what two forms of phosphorylase?
- Phosphorylase a which has a phosphoryl group esterified to Ser 14 in each of its subunits
- Phosphorylase b which lacks these phosphoryl groups
What are phosphorylase’s allosteric inhibitor(s)?
- ATP
- G6P
- Glucose
What is glycogen phosphorylase regulated by?
Both allosteric interactions and by covalent modifications
What is glycogen phosphorylase regulated by?
Both allosteric interactions and by covalent modifications
What are phosphorylase’s allosteric activator(s)?
AMP
What do the structures of phosphorylase a and b both have?
1) N-terminal –> Interface domain: Covalent modification site (Ser 14), allosteric effector site, and glycogen-binding subdomain which contains the “glycogen storage site”
2) C-terminal domain: Catalytic site located at the center of the subunit where two subdomains come together
How does the glycogen storage site presumably increase the catalytic efficiency of glycogen phosphorylase?
By permitting it to phosphorylate many glucose residues on the same glycogen particle without having to dissociate and reassociate completely between catalytic cycles
What is an essential cofactor for glycogen phosphorylase
Pyridoxal-5’-phosphate (PLP) is a vitamin B6 derivative covalently linked to glycogen phosphorylase near the enzyme’s active site
What does the glycogen phosphorylase reaction result in?
The cleavage of the C1-O1 bond from a nonreducing terminal glycosyl unit of glycogen, yielding G1P
What is the reaction mechanism of glycogen phosphorylase?
1) Formation of an E x Pi x Glycogen ternary complex
2) Formation of a shielded oxonium ion intermediate from the alpha-linked terminal glycosyl residue involving acid catalysis by Pi as facilitated by proton transfer from PLP. The oxonium ion has a half-chair conformation.
3) Reaction of Pi with oxonium ion with overall retention of configuration about C1 to form alpha-D-glucose-1-phosphate. The glycogen, which has one less residue than before, cycles back to step 1.
How does the glycogen storage site increase the catalytic efficiency of phosphorylase?
By permitting it to phosphorylize many glucose residues on the same glycogen particle without having to dissociate and reassociate completely between catalytic cycles
The fact that the glycogen phosphorylase reaction proceeds with retention of configuration suggests what?
That the phosphorolysis occurs via a double displacement mechanism (two sequential nucleophilic substitutions, each occurring with inversion of configuration) involving a covalent glucosyl-enzyme intermediate *SN1
What imitates the transient intermediate in the glycogen phosphorylase reaction?
1,5-Gluconolactone (therefore, it acts as an inhibitor)
What does phosphoglucomutase convert?
Converts G1P, which was converted by phosphorylase from glycosyl units of glycogen, to G6P - either for entry into glycolysis in muscle or hydrolysis to glucose in liver
How is the phosphoglucomutase reaction similar to that catalyzed by phosphoglycerate mutase?
A phosphoryl group is transferred from the active phosphoenzyme to G6P, forming glucose 1,6-bisphosphate (G1,6P), which then phosphorylates the enzyme to yield G1-
