Glycogenolysis

Glycogen

Glycogenolysis

Glycogenolysis refers to the metabolic pathway responsible for the breakdown of glycogen – a polysaccharide form of glucose storage – into glucose-1-phosphate and glycogen(n-1). This breakdown involves the sequential removal of glucose monomer units, achieved through phosphorolysis, a process facilitated by the enzyme glycogen phosphorylase[1].

Mechanism

Glucose

The core reaction that underpins glycogenolysis can be expressed as:

glycogen(n residues) + Pi ⇌ glycogen(n-1 residues) + glucose-1-phosphate

In this process, the enzyme glycogen phosphorylase substitutes a phosphoryl group for the α[1→4] linkage, which in turn cleaves the bond connecting a terminal glucose residue to a glycogen branch. The generated glucose-1-phosphate is then transformed into glucose-6-phosphate by the action of phosphoglucomutase.

As glucose residues continue to undergo phosphorolysis, this occurs until only four residues are left before a glucose branched with an α[1→6] linkage. At this juncture, the glycogen debranching enzyme comes into play, transferring three of the remaining four glucose units to the end of another glycogen branch. The exposure of the α[1→6] branching point permits its hydrolysis by α[1→6] glucosidase, resulting in the removal of the branch's final glucose residue as glucose. Notably, this is the singular instance where the end-product of glycogen metabolism isn't glucose-1-phosphate. This glucose residue is then phosphorylated into glucose-6-phosphate, thanks to the enzyme hexokinase.

Glucose-6-phosphate

Function

Glycogenolysis predominantly occurs within the cells of muscle and liver tissues. The process is driven by a combination of neural and hormonal cues, and holds significance in situations like the fight-or-flight response and in maintaining consistent glucose levels in the bloodstream.

• In myocytes (muscle cells): The degradation of glycogen supplies an immediate reservoir of glucose-6-phosphate, primed for glycolysis, which in turn powers muscle contractions.
• In hepatocytes (liver cells): Glycogenolysis mainly focuses on releasing glucose into the bloodstream, facilitating its uptake by various other cells. The phosphate group attached to glucose-6-phosphate is detached via the glucose-6-phosphatase enzyme – an enzyme absent in myocytes. The resultant glucose then leaves the cell through GLUT2 facilitated diffusion channels located in the hepatocyte cell membrane.

Regulation

The process of glycogenolysis is closely regulated by hormones, most notably by glucagon and insulin, based on blood glucose concentrations. Moreover, during the fight-or-flight response, it is spurred by epinephrine. In myocytes, the degradation of glycogen can be further prompted by neural signals[2].

Clinical significance

In medical emergencies linked to diabetes, especially when oral sugar intake isn't feasible, glucagon can be administered parenterally (via an intravenous route). Intramuscular administration is another viable method for delivering glucagon.

See also

• Glycogenesis
• Gluconeogenesis
• Glucose metabolism

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Glycogenolysis

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  Glycogen

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  Beta-D-Glucose

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  Alpha-D-Glucospyranose-6-Phosphate