GLYCOGENOLYSIS | GLYCOGEN METABOLISM

GLYCOGENOLYSIS

In this blog we talked about glycogenolysis or glycogen metabolism. 

The degradation of stored glycogen in liver and muscle constitutes glycogenolysis. The pathways for the synthesis and degradation of glycogen are not reversible. An independent set of enzymes present in the cytosol carry out glycogenolysis. Glycogen is degraded by breaking -1,4- and -1,6-glycosidic bonds.

1. Action of glycogen phosphorylase : The - 1,4-glycosidic bonds (from the non-reducing ends) are cleaved sequentially by the enzyme glycogen phosphorylase to yield glucose 1-phosphate. This process—called phospho- rolysis—continues until four glucose residues remain on either side of branching point (-1,6- glycosidic link). The glycogen so formed is known as limit dextrin which cannot be further degraded by phosphorylase. Glycogen phosphorylase possesses a molecule of pyridoxal phosphate, covalently bound to the enzyme.

2. Action of debranching enzyme : The branches of glycogen are cleaved by two enzyme activities present on a single polypeptide called debranching enzyme, hence it is a bifunctional enzyme. Glycosyl 4 : 4 transferase (oligo -1,4 1,4 glucan transferase) activity removes a fragment of three or four glucose residues attached at a branch and transfers them to another chain. Here, one -1,4-bond is cleaved and the same -1,4 bond is made, but the places are different.  Amylo -1,6-glucosidase breaks the -1,6 bond at the branch with a single glucose residue and releases a free glucose.  The remaining molecule of glycogen is again available for the action of phosphorylase and debranching enzyme to repeat the reactions stated in 1 and 2.

3. Formation of glucose 6-phosphate and glucose : Through the combined action of glycogen phosphorylase and debranching enzyme, glucose 1-phosphate and free glucose in a ratio of 8 : 1 are produced. Glucose 1-phosphate is converted to glucose 6-phosphate by the enzyme phosphoglucomutase.

The fate of glucose 6-phosphate depends on the tissue. The liver, kidney and intestine contain the enzyme glucose 6-phosphatase that cleaves glucose 6-phosphate to glucose. This enzyme is absent in muscle and brain, hence free glucose cannot be produced from glucose 6-phosphate in these tissues. Therefore, liver is the major glycogen storage organ to provide glucose into the circulation to be utilised by various tissues.

In the peripheral tissues, glucose 6-phosphate produced by glycogenolysis will be used for glycolysis. It may be noted that though glucose 6-phosphatase is absent in muscle, some amount of free glucose (8-10% of glycogen) is produced in glycogenolysis due to the action of debranching enzyme (-1,6-glucosidase activity).

Glycogenolysis