23 Glycogenolysis

Dr.Vikram Raval

epgp books

   

 

 

 

GLYCOGENOLYSIS

 

Objectives

  1. To understand the breakdown of glycogen.
  2. To understand the role of glycogen phosphorylase in glycogen breakdown.
  3. To understand the role of Glycogen Debranching enzyme

   

Introduction

  • The biological degradation of glycogen is termed as glycogenolysis.
  • Glycogen is a highly branched, large polymer of glucose molecules linked along its main line by α-1, 4 glycosidic linkages; branches arise by α-1,6 glycosidic bond at about every tenth residues.

Fig: 25.1 STRUCTURE OF GLYCOGEN

 

  • Glycogen founds in the cytoplasm as granules. Granules also contain the enzymes and regulatory proteins which is required for its synthesis and degradation.It acts as an important energy reserve for the body. It is stored in the liver and skeletal muscle.Glycogen stored in the muscles will be utilized for the energy requirement of muscles only, while glycogen stored in the liver will be used for the energy requirement of the rest of the body.
  • Regulation of glycogenesis and glycogenolysis is very important in maintaining the glycogen homeostasis. These two processes are commonly regulated. Hormones which stimulate glycogenolysis (e.g. glucagon,  cortisol, epinephrine, norepinephrine) concurrently inhibit glycogenesis. On the other hand, insulin, which promotes the body to store glycogenesis, is inhibiting glycogenolysis.
    • Glycogen is degraded by two different pathways. In the first, glucose is released in muscles to fuel its contraction or it is released in liver to transport it in to the blood. It is catalysed by the Glycogen phosphorylase and Debranching enzyme. In the second pathway, glycogen is degraded to glucose within the lysosome by the enzyme α-glucosidase and acid maltase.

     

    • Glycogen metabolism is very important because it facilitate the blood glucose level to be maintained between meals (liver glycogen) and also act as an energy reserve for muscular activity. The maintenanceof blood glucose is essential in order to supply energy to tissues.

    STEPS OF GLYCOGENOLYSIS

 

Glycogenolysis requires2main enzymes. Glycogenolysisoccurs by a different pathway from glycogenesis.

  1. Glucose-1-phosphate formation from non reducing end of glycogen by Glycogen phosphorylase
  1. Removal of α-1,6 branches from glycogen by Glycogen Debranching enzyme
  1. Glucose-6-phosphate formation from Glucose-1-phosphateby Phosphoglucomutase.

Fig: 24.2OVERVIEW OF GLYCOGENOLYSIS

 

 

 

1. Glucose-1-phosphate formation from non reducing end of glycogen by Glycogen phosphorylase

  • Glycogen is  broken-down  in  to  Glucose-1-Phosphate  (G1P)  by  Glycogen

        Phosphorylase. It is carried out by phosphorolysis reaction. Phosphorolysis  reaction involves the cleavage of larger molecules into smaller molecules. It uses phosphate for the cleavage. Such breakdown of bonds by the addition of orthophosphate is referred to as phosphorolysis. A hydrolysis reaction also involves the same process but it uses water instead of phosphate for the cleavage of bond.

 

Fig: 24.3 Formation of G- 1-P from glycogen

  • Cleavage by phosphorolysis is energetically favourable because released glucose is phosphorylated. While hydrolytically release of sugar needs to be phosphorylated before enters into the glycolytic pathway.
  • Glycogen phosphorylase act on exoglycosidic bond. Pyridoxal phosphate is an necessary cofactor in the glycogen phosphorylase reaction. This cofactor is linked to lysine 680 of the enzyme.
  • Glycogen phosphorylase will act repeatedly on non-reducing ends of a glycogen chain. Glycogen phosphorylase can act continuously until it reaches 4 glucose away from α 1-6 branch point.
  • Glycogen phosphorylase is an allosteric enzyme. AMP acts as an allosteric activator while ATP, G6P and glucose acts as an allosteric inhibitor. Glycogen phosphorylase is also regulated by covalent modification. ( For further details please refer module:26 , regulation of glycogen degradation)
  • Generally in the structure of glycogen about 1 in 10 residues is branched. In such situation phosphorylase enzyme cannot degrade glycogen independently. It will stop to a halt after the release of six glucose molecules per branch.

 

2. Removal of α-1,6 branches from glycogen by Glycogen Debranching enzyme

  • In glycogen, α- 1-6 glycosidic bonds at the branch point are not susceptible to cleavage by glycogen phosphorylase while it can act continuously until it reaches four glucose away from α 1-6 branch point. Thus further degradation of glycogen chain by glycogen phosphorylase occurs only after the action of a glycogen debranching enzyme.
  • Glycogen debranching enzyme shows two different activities.

    o Transferase activity

o α 1à6 glucosidase activity

  • In transferase activity, the enzyme removes and transfers terminal 3 of the 4 glucose residues. It transfers this moiety intact to the non reducing end of another branch. It involves cleaving of an α (1à4) linkage and formation of new α (1à4) linkage in another branch. This action leaves a single glucose at the α1,6 branch.
  • In α 1à6 glucosidase activity, enzyme removes the single glucose residue which is remaining at branch point by an alpha (1à6 glucosidase activity of the same debranching enzyme.
  • 91 % of the glycogen residues are converted to Glucose-1-phosphate by the combined activity of glycogen phosphorylase and glycogen debranching enzyme.

 

Remaining about 8 % are converted to glucose by the α 1à6 glucosidase activity of the glycogen debranching enzyme.

 

 

3. Glucose-6-phosphate formation from Glucose-1-phosphate by Phosphoglucomutase

  • Glucose-1-phosphate is converted to Glucose-6-phosphate by Phosphoglucomutase.
  • Active site of the active Phosphoglucomutase molecule has a phosphorylated serine residue. The phosphoryl group istransferred from the amino acid serine to the hydroxyl group (C-6) of glucose 1-phosphate. It result in to the formation of intermediate called glucose1, 6-bisphosphate. The phosphoryl group from the C-1 of glucose 1, 6-bisphosphate is then transfer to the serine residue of the enzyme. It results in to the formation of glucose 6-phosphate and the regeneration of the enzyme.
  •  This reaction is reversible. It allows the inter conversion of Glucose-6-Phosphate and Glucose-1-Phosphate. This isvery important. Phosphoglucomutase is also required to form.

 

 

you can view video on Glycogenolysis

 

References

  • Peter J. Roach, Anna A. Depaoli-Roach, Thomas D. Hurley, Vincent S. Tagliabracci (2012) Glycogen and its metabolism: some new developments and old themes . Biochemical Journal, 441 (3) 763-787; DOI: 10.1042/BJ20111416
  • Roach PJ, Depaoli-Roach AA, Hurley TD, Tagliabracci VS (2012) Glycogen and its metabolism: some new developments and old themes. Biochem J 441: 763–787. doi: 10.1042/BJ20111416
  • Wilson WA, Roach PJ, Montero M, Baroja-Fernandez E, Munoz FJ, Eydallin G, et al. Regulation of glycogen metabolism in yeast and bacteria. Fems Microbiol Rev. 2010;34(6):952–985.

 

Web site

  • http://www.wiley.com/college/fob/quiz/quiz15/15-20.swf
  • https://www.tamu.edu/faculty/bmiles/lectures/Glycogen%20Metabolism.pdf
  • http://themedicalbiochemistrypage.org/glycogen.php
  • https://en.wikibooks.org/wiki/Principles_of_Biochemistry

 

Books

  • Harper’sIllustrated Biochemistry by Robert K.. Murray, Daryl K. Granner, Peter A. Mayes, 26th Edition (2003)
  • Lehninger’S Principle of Biochemistry David L. Nelson and Michael M. Cox,5th Edition (2008)
  • Instant Notes: Biochemistry, 2nd Edition, B.D. Hames & N. M. Hooper (2005)
  • Textbook of Biochemistry, 4th Edition Donald Voet, Judith G. Voet(2011)