Glycogen Degradation Part I

Glycogen is a highly branched homopolymer composed entirely of glucose residues.
While present in all tissues, the most significant physiological stores are found in the liver and skeletal muscle.
The role of glycogen varies by tissue type:
- Liver Glycogen: The liver breaks down its stores to release glucose into the bloodstream, maintaining blood glucose levels to provide energy for the brain and red blood cells.
- Muscle Glycogen: These stores are mobilized locally to provide the necessary energy for muscle contraction.

Glycogen molecules utilize two primary types of glycosidic bonds:
- $\alpha$ -1,4 linkage: The primary bond connecting glucose units in a linear chain.
- $\alpha$ -1,6 linkage: The bond responsible for creating branch points in the polymer.
The structure features multiple nonreducing ends, which allow for rapid mobilization of glucose units during degradation.

Phosphorolysis is the primary reaction in glycogen degradation, catalyzed by glycogen phosphorylase.
The enzyme acts on the nonreducing ends of the glycogen polymer.
The reaction utilizes orthophosphate ( $HPO_4^{2-}$ ) to cleave the $\alpha$ -1,4 glycosidic linkage.
The chemical reaction is represented as:
- $\text{Glycogen (n residues)} + HPO_4^{2-} \rightarrow \text{Glucose 1-phosphate} + \text{Glycogen (n-1 residues)}$
Unlike simple hydrolysis, phosphorolysis preserves the energy of the glycosidic bond by producing a phosphorylated sugar, which prevents the glucose from leaving the cell.

Glycogen phosphorylase alone cannot degrade a glycogen molecule entirely because it ceases activity four residues away from an $\alpha$ -1,6 branch point.
The remodeling process required to handle branches involves two additional enzymatic activities:
- Transferase: This enzyme shifts a block of three glycosyl residues from one outer branch to another, exposing a single glucose residue attached by an $\alpha$ -1,6 glycosidic bond.
- $\alpha$ -1,6-Glucosidase (Debranching Enzyme): This enzyme catalyzes the hydrolysis of the remaining $\alpha$ -1,6-linked glucose residue.
In the final debranching step, a water molecule ( $H_2O$ ) is used to release a molecule of free glucose, rather than a phosphorylated glucose.

The Glucose 1-phosphate produced by phosphorylase must be converted into Glucose 6-phosphate to enter the main metabolic pathways.
This isomerization is catalyzed by the enzyme Phosphoglucomutase.
The reaction mechanism involves a phosphorylated enzyme intermediate:
1. The enzyme, which carries a phosphoryl group on a specific Serine residue, transfers that group to the C-6 hydroxyl group of Glucose 1-phosphate.
2. This creates a temporary intermediate: Glucose 1,6-bisphosphate.
3. The phosphoryl group at the C-1 position of the intermediate is then transferred back to the Serine residue of the enzyme.
4. The final product is Glucose 6-phosphate.
The functional groups involved in this process include $-CH_2OH$ and $-OPO_3^{2-}$ .

The metabolic fate of Glucose 6-phosphate depends on the tissue and the presence of specific enzymes.
The liver contains the hydrolytic enzyme Glucose 6-phosphatase, which is notably absent from skeletal muscle and most other tissues.
The function of Glucose 6-phosphatase in the liver is to generate free glucose from Glucose 6-phosphate.
This free glucose is then released into the blood to meet the metabolic demands of other tissues, particularly the brain and red blood cells.
Because muscle lacks this enzyme, the Glucose 6-phosphate produced from muscle glycogen is retained within the muscle cell to be used as a substrate for glycolysis to power contraction.