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Glycogenolysis is the breakdown of glycogen (n) to glucose-6-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase.
Glycogen is synthesized of a - 1, 4 and&nbsp;a, 1, 6-glycosidic bonds. It is the storage form of glucose when the body is supplied with a high glucose diet. In low glucose levels, glycogen is reversed back to the form of glucose by the process of glycogenolysis. This process is under high control of hormonal responses in the adrenaline-induced fight-or-flight response.&nbsp;
<h2 style="text-align: justify;">1. Steps of Glycogenolysis -</h2>
<h3>1.1 Degradation of Glycogen to Glucose 1 phosphate :</h3>
Glycogen is cleaved to the glucose 1 phosphate by the glycogen phosphorylase. Glycogen phosphorylase was the first allosteric enzyme to be discovered by Carl and Gerty Cori. It is present in the form of the homodimer. It is regulated allosterically by the structural change in phosphorylation at the serine residue and with the conversion of phosphorylase-B to phosphorylase-A. It is inhibited by ATP, G-6-P, and glucose and activated by AMP.
Along cleft in the phosphorylase connects with the glycogen which covers around 5 glucose residues so thereby phosphorylase cleaves 5 residues away from the branch point. In mammals muscle, liver, and brain have the major isozymes of glycogen phosphorylase.
Glycogen Phosphorylase binds with the cofactor pyridoxal 5&rsquo; phosphate at its active site which is a vitamin B-6 derivative and forms a Schiff base between its aldehyde group and E amino group of Lys.&nbsp;
The reaction catalyzed by this enzyme is -&nbsp;
<img style="display: block; margin-left: auto; margin-right: auto;" src="https://vediphlie-aws.s3.ap-south-1.amazonaws.com/Degradation_of_glycogen_2754ae0678.PNG" alt="Degradation of glycogen" />
Fig.: Degradation of glycogen
The overall reaction for the breakdown of glycogen to glucose-1-phosphate is:&nbsp;
<img src="https://vediphlie-aws.s3.ap-south-1.amazonaws.com/1_59c4ef3751.PNG" alt="" />
Here, glycogen phosphorylase cleaves the bond linking a terminal glucose residue to a glycogen branch by substitution of a phosphoryl group for the &alpha;[1&rarr;4] linkage.
<h3 style="text-align: justify;">1.2 Importance of Glycogen Phosphorylase :</h3>
1. The target for the treatment of type 2 diabetes by inhibiting the release of glucose from the glycogen storage of the liver.
2. Mutation in glycogen phosphorylase causes McArdle&rsquo;s disease showing symptoms of muscle weakness and muscle pain (myalgia).
3. Mutation in the liver isoform of glycogen phosphorylase causes Hers&rsquo; disease, which shows symptoms of hypoglycemia.
4. The brain isoform of glycogen phosphorylase (PYGLB) has been proposed as a biomarker for gastric cancer.
<h3 style="text-align: justify;">1.3 Debranching enzyme :</h3>
Debranching phosphorolysis occurs till the 5 residues from the&nbsp;a(1-6 ) branch point. Glycogen debranching enzyme act as a(1-4) transglycosylase which transfers the&nbsp;a(1-4) trisaccharide chain to the non reducing of another branch. So normally the first glucosyl residue connected with&nbsp;a (1-6) residue is simply hydrolyzed and the rest of the (1-4) attached glucosyl residues are converted to G-1-P. The debranching enzyme has two separate active sites for transferring and for hydrolysis of&nbsp;a-1-6 residue.&nbsp;
<img style="display: block; margin-left: auto; margin-right: auto;" src="https://vediphlie-aws.s3.ap-south-1.amazonaws.com/Glycogen_Debranching_Enzyme_73a024e9b4.PNG" alt="Glycogen Debranching Enzyme" />
Fig.: Glycogen Debranching Enzyme
<h3 style="text-align: left;">1.4 The activity of Debranching Enzyme :</h3>
So normally glycogen phosphorylase works in the body on glucose requirement in the body which catalyzes its reaction fast. If the further requirement is beyond this point then the debranching enzyme comes into action which is a relatively slower reaction.
<h3 style="text-align: justify;">1.5&nbsp;&nbsp;The fate of Glucose -1- Phosphate :</h3>
Glucose -1- Phosphate formed by the phosphorylase has two fates according to the requirement of the body. In muscles, glucose -1- phosphate is converted to glucose -6- phosphate by the enzyme phosphoglucomutase. This glucose -6- phosphate is redirected towards glycolysis and provides energy. Hereby it bypasses the activation step of glucose to glucose-6-phosphate hence saving one molecule of ATP. In high working muscles, the net yield of ATP per glucose to lactate is 3 rather than 2.&nbsp;
<h2 style="text-align: justify;">2. The overall equation is -</h2>
Glycogen(n glucose residues) + 3 ADP + 3 Pi &rarr; glycogen + 2 lactate + 3 ATP(n-1 glucose residues)
In the liver glucose -6- phosphate formed from glucose -1- phosphate, is dephosphorylated by the enzyme glucose -6- phosphatase, and free glucose are released in blood for uptake by other cells by the glucose transporters present in the cell membrane.&nbsp;
Glucose-6-phosphate + H2O&nbsp; &nbsp; &rarr;&nbsp; &nbsp;Glucose + Pi
<h2 style="text-align: left;">3. Regulation of glycogen metabolism -</h2>
This enzyme is allosterically regulated by AMP, ATP, And glucose-6-phosphate. ATP and glucose-6-phosphate produce a negative effect on the cooperativity of substrate binding. While AMP has a positive effect.&nbsp;
The enzyme exists in only two conformations designated R and T. These conformations are in equilibrium R &harr; T. The substrates bind when the enzyme is in the R state. Positive allosteric effectors bind to the R state and stabilize it shifting the equilibrium to the left. Negative allosteric effectors bind to the T state and stabilize it shifting the equilibrium to the right.
This enzyme binds inorganic phosphate cooperatively. This allows the enzyme&rsquo;s activity to increase by great amounts over a narrow range of substrate concentrations&nbsp;
<h3 style="text-align: justify;">3.1 Regulation of glycogenolysis is by the phosphorylation cascades :</h3>
The conversion of inactive glycogen phosphorylase -B to active glycogen phosphorylase -A is dependent upon the phosphorylation cascade through cyclic AMP-dependant Protein Kinase A (PKA) which is a Ser/Thr kinase which in turn is activated by cyclic AMP.
Both hormones Adrenaline (epinephrine, which is released in response to a threat or stress - the &lsquo;fight-or-flight&rsquo; response) and glucagon, (which is released by pancreatic alpha cells in response to low blood glucose levels), stimulate glycogenolysis by binding to their respective receptors (both of which are G-protein coupled receptors) which activates membrane-localized protein adenyl cyclase. Adenyl cyclase forms cAMP from ATP then activates PKA. Which stimulates glycogen phosphorylase and inhibits glycogen synthase.
Insulin has a counter effect on glycogenolysis. It inhibits glycogenolysis by activating protein phosphatase 1 (PP1) and the enzyme phosphodiesterase which both contribute to the inactivation of glycogen phosphorylase.&nbsp;
<img style="display: block; margin-left: auto; margin-right: auto;" src="https://vediphlie-aws.s3.ap-south-1.amazonaws.com/Regulation_of_Glycogenolysis_a568e1cb21.PNG" alt="Regulation of Glycogenolysis" />
Calcium ions
Calcium ions or cyclic AMP (cAMP) act as secondary messengers which are an example of the negative control. The calcium ions activate phosphorylase kinase which activates glycogen phosphorylase and inhibits glycogen synthase.

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In the Glycogenolysis topic of Biochemistry; we will cover the Steps of Glycogenolysis and the Regulation of glycogen metabolism. Explore more!

Glycogenolysis -  Steps & Regulation of Glycogen Metabolism

Glycogenolysis is the breakdown of glycogen (n) to glucose-6-phosphate and glycogen (n-1). In the Glycogenolysis topic of Biochemistry; we will cover the Steps of Glycogenolysis and the Regulation of glycogen metabolism. Explore more!

Glycogenolysis

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