Question

BIOCHEMISTRY: Explain the enzyme reactions involved in glycogen degradation.

Answer 1

Glycogen degradation also known as Glycogenolysis requires four enzyme activities: First one is to degrade glycogen, two to reconstruct glycogen hence it will remains a substrate for further degradation, and second one to convert the product of glycogen breakdown into further metabolism.

1. Glycogen phosphorylase is the central enzyme in glycogen breakdown, it will split the substrate by the addition of orthophosphate (P_i) to yield glucose 1-phosphate. The cleavage of a bond by the addition of orthophosphate is called to as phosphorolysis.

Key features: short way to remember the key points.

- degrades glycogen; uses a free P to break the bond and make G1P
- can only work up to 4 glucose residues from a branching point
- P attacks at the C1 position, releasing a G1P
- DOES NOT USE ATP to phosphorylate
- requires vitamin B₆, pyridoxal phosphate
- Phos'd is ACTIVE (a), dephos'd is INACTIVE (b)
- Phos (a) is inhibited by creatine-P in muscle and glucose in liver
- Phos (b): no allostery in liver, but (+) by AMP in muscle and (-) by ATP and G6P
- AMP, ATP, and G6P all compete for binding

Phosphorylase catalyzes the sequential removal of glycosyl residues from the nonreducing ends of the glycogen molecule (the ends with a free 4-OH groups; Orthophosphate splits the glycosidic linkage between C-1 of the terminal residue and C-4 of the adjacent one. Specifically, it cleaves the bond between the C-1 carbon atom and the glycosidic oxygen atom, and the α configuration at C-1 is retained.

Glucose 1-phosphate released from glycogen can be readily converted into glucose 6-phosphate,by the enzyme phosphoglucomutase.

2. Glycogen phosphorylase, the key debranching enzyme in glycogen breakdown. The α-1,6-glycosidic bonds at the branch points are not susceptible to cleavage by phosphorylase. Phosphorylase stops cleaving α-1,4 linkages when it reaches a terminal residue 4 residues away from a branch point. Glycogen degradation by the phosphorylase stops after the release of six glucose molecules per branch. Two additional enzymes, a transferase and α-1,6-glucosidase, reconstructing the glycogen for continued degradation by the phosphorylase (see below figure). The transferase shifts a block of three glycosyl residues from one outer branch to the other. This transfer exposes a single glucose residue joined by an α-1,6-glycosidic linkage. α-1,6-Glucosidase, also known as the debranching enzyme, hydrolyzes the α-1, 6-glycosidic bond, resulting in the release of a free glucose molecule.

This free glucose molecule is phosphorylated by the glycolytic enzyme hexokinase. Thus, the transferase and α-1,6-glucosidase convert the branched structure into a linear one, which paves the way for further cleavage by phosphorylase.

Key features: short way to remember the key points.

- degrades glycogen; degrades branch points
- transfers 3 glucose residues to another branch
- also liberates a free glucose
- unregulated
- 3 functionalities:
1) breaks a(1,4) bonds
2) transfers the 3 glucose residues to a free end of a long chain
3) breaks a(1,6) bonds to liberate free glucose

3. G1P converted into G6P by phosphoglucomutase.

The overall process can be depicted in a graphical way as

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