Glycogenolysis pathway and its regulation a detailed study.

glycogenolysis detailed study. Glycogen breakdown pathway explained each step in detail. regulation of glycogenolysis pathway. allosteric regulation, hormonal regulation and calcium ion regulation.

1. Presented by Anjali K R

2. GLYCOGENOLYSIS Breakdown of glycogen to glucose is called as glycogenolysis 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 . G lycogen is degraded by breaking α ( 1- 4)- and α ( 1,6)- glycosidic bonds

3. Action of glycogen phosphorylase The α -1,4-glycosidic bonds (from the non-reducing ends ) are cleaved sequentially by the enzyme glycogen phosphorylase to yield glucose1-phosphate . This process is called phosphorolysis , Continues until four glucose residues remain on either side of branching point ( α -1,6 glycosidic link). The glycogen so formed is known as limit dextrin which cannot be further degraded by phosphorylase .

4. 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 α - 1,4 --> l , 4 glucan transferase ) activity removes a fragment of three glucose residue from the four glucose residues attached at a branch and transfers them to another chain. Here, one α -1,4-bond is cleaved and the same α -1,4 bond is made, but the places are different.

5. Amylo α-1,6-glucosidase or glucosidase , cleaves the remaining alpha- 1 , 6 linkage , producing a free glucose molecule and a linear chain of glycogen. The remaining glycogen is again available for the action of phosphorylase and debranching enzyme to repeat the reactions stated in 1 and 2.

6. 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 .

7. 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.

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

9. Regulation of glycogenolysis A good coordination and regulation of glycogen synthesis and its degradation are essential to maintain the blood glucose levels . Glycogenesis and glycogenolysis are, respectively , controlled by the enzymes glycogen synthase and glycogen phosphorylase . Regulation of these enzymes is accomplished by three mechanisms 1 . Allosteric regulation 2 . Hormonal regulation 3 . lnfluence of calcium.

10. Allosteric regulation of glycogen metabolism G lycogen breakdown is enhanced when glucose concentration and energy levels are low. When there is high demand for  ATP   (low [ ATP ], low [ Glucose-6-P ], and high [AMP]), glycogen   phosphorylase is stimulated and  glycogen synthase  is  inhibited , so flux through this pathway favours Glycogenolysis .

11. Effect of Ca2+ ions on glycogenolysis Insulin stimulated the activity of  glycogen synthase  in muscle in the absence of extracellular  calcium . It is concluded that  glycogen synthase  is under the control of  calcium  in the glycogen  storage tissues.

12. Hormonal Regulation The overall effect of hormones on glycogen metabolism is that an elevated glucagon or epinephrine level increases glycogen degradation , whereas an elevated insulin results in increased glycogen synthesis .

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