First stage: phosphorolysis reaction
The initial and most extensive stage of molecule cleavage is carried out by the enzyme glycogen phosphorylase. This enzyme acts on the so-called non-reducing ends of the polymer chain.
The process proceeds via a phosphorolysis mechanism. Unlike hydrolysis, where water is used to break chemical bonds, here an inorganic phosphate molecule (orthophosphoric acid, $H_3PO_4$) enters the reaction.
The enzyme sequentially attacks and cleaves $\alpha$-1,4-glycosidic bonds between glucose residues. As a result of each such cleavage, a single carbohydrate fragment is detached from the polymer molecule and immediately becomes bound to a phosphate group. Thus, the direct product of this reaction is glucose-1-phosphate.
However, glycogen phosphorylase has a strict spatial limitation. The enzyme molecule is quite bulky and cannot get close to the branching points of the polymer. As soon as exactly four glucose residues remain before the branching point (where the carbohydrate chains are connected differently), glycogen phosphorylase completely ceases its activity in this region.
Second stage: side branch transfer
Since glycogen phosphorylase has stopped, another specialized enzyme comes into play — oligosaccharide transferase. Its main task is to reconstruct the molecule and make it accessible for cleavage again.
The mechanism of action of this enzyme boils down to a large-scale relocation of carbohydrate fragments:
- The enzyme captures an entire block consisting of exactly three glucose residues. These are the very residues that remained unreleased on the side branch after the previous enzyme stopped.
- The captured block is transferred from the side branch to the free non-reducing end of the main chain.
As a result of this major rearrangement, the main carbohydrate chain is significantly elongated. Most importantly, after the transfer of the three-residue block, direct access is opened to the $\alpha$-1,6-glycosidic bond, which forms the branching point itself. Now the polymer structure is modified so that there are no further obstacles to subsequent enzymatic reactions.
Regulation: how breakdown is switched on and off
The rate of the processes described above depends on the state of the main breakdown enzyme. Glycogen phosphorylase can exist in two fundamentally different forms, the transition between which is carried out by chemical modification of the protein molecule.
- Active form (Glycogen phosphorylase-℗). The enzyme is in its working state when phosphorylated. The activation process is triggered by a special enzyme — phosphorylase kinase (which must itself be in an active state). The kinase takes a phosphate group from an ATP molecule and transfers it to the glycogen phosphorylase structure.
- Inactive form (Glycogen phosphorylase-OH). The enzyme is "turned off" when dephosphorylated. This process is handled by PP-1 (glycogen granule-associated phosphoprotein phosphatase). This enzyme carries out a hydrolysis reaction: with the participation of a water molecule ($H_2O$), the phosphate bond is broken, and inorganic phosphate ($P_i$) is cleaved from the enzyme protein.
Thus, the alternation of phosphorylation and dephosphorylation reactions serves as a precise molecular switch that turns on or off the generation of glucose-1-phosphate depending on current demands.
Briefly: answers to topical questions
Which enzyme breaks $\alpha$-1,6-glycosidic bonds at glycogen branching points?
The enzyme that breaks $\alpha$-1,6-glycosidic bonds at glycogen branching points is amylo-1,6-glucosidase, the debranching enzyme.
First, oligosaccharide transferase transfers a block of three glucose residues from the side branch to the non-reducing end of the main chain, which elongates the main chain and opens access to the $\alpha$-1,6-bond.
A defect in amylo-1,6-glucosidase leads to Type III glycogen storage disease (Cori disease), characterized by glycogen accumulation in skeletal muscles with short outer branches—limit dextrins.
Which hormones stimulate glycogen breakdown in the liver and muscles?
Glycogen breakdown is stimulated by adrenaline and glucagon.
- In the liver, glucagon activates glycogen phosphorylase and thereby mobilizes glycogen in the postabsorptive state and during fasting.
- Adrenaline in acute stress triggers a cascade of reactions via the adenylate cyclase system, leading to the phosphorylation of enzymes: glycogen phosphorylase is converted into the active form, and glycogen synthase into the inactive form.
- In the postabsorptive state, glucagon in the liver and adrenaline in muscles trigger the adenylate cyclase cascade, which leads to the phosphorylation of glycogen synthase and glycogen phosphorylase.
To easily remember the essence of the second stage, use the phrase "Transfer three, leave one." Oligosaccharide transferase transfers a block of exactly three glucose residues, opening access to the remaining branching point.
Class and exam questions
What is the difference between phosphorolysis and hydrolysis?
During phosphorolysis, inorganic phosphate ($H_3PO_4$) rather than a water molecule is used to break the chemical bond between glucose residues. Due to this, the cleaved fragment is immediately converted into a phosphorylated product (glucose-1-phosphate).
Why can't glycogen phosphorylase cleave the whole molecule?
The enzyme has spatial limitations and stops the cleavage of monosaccharides (breaking $\alpha$-1,4-bonds) when 4 glucose residues remain before the branching point. Beyond that, the structure of the branch itself hinders it.
How is glycogen phosphorylase activated?
It transitions into the active form by attaching a phosphate group. This reaction is carried out by active phosphorylase kinase, which transfers phosphate from an ATP molecule to the enzyme.
Which enzyme turns off glycogen breakdown?
Inactivation is carried out by PP-1 (glycogen granule-associated phosphoprotein phosphatase). It hydrolyzes the phosphate bond, converting the enzyme into the dephosphorylated (Glycogen phosphorylase-OH) inactive form.
What else to study on this topic
- Mechanism of destruction of the exposed $\alpha$-1,6-bond (action of the debranching enzyme)
- Cascade mechanism of phosphorylase kinase activation
- Fate of the formed glucose-1-phosphate
- Hormonal regulation of phosphorylation processes
- Differences between glycogen granule-associated PP-1 and other cellular phosphatases
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