Glycogenesis and glycogenolysis

biochemistry

1. GLYCOGENESIS AND GLYCOGENOLYSIS Lubna S Subair S6 BT Zoology core

2. GLYCOGENESIS

3. INTRODUCTION 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. It occurs in the cytoplasm as granules . Granules also contain the enzymes and regulatory proteins which is required for its synthesis and degradation .

4. 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.

5. STEPS OF GLYCOGENESIS Glycogen synthesis requires 3 main enzymes. Glycogenesis occurs by 1 . UDP-glucose formation by UDP-glucose pyrophosphorylase 2. Glycogen synthesis by glycogen synthase 3. Glycogen Branching

6. UDP-glucose formation by UDP-glucose pyrophosphorylase Glucose is activated before polymerisation in to glycogen. Hexokinase enzyme (In muscles) or glucokinase enzyme (in liver) catalyzes the phosphorylation of glucose to glucose-6- phosphate. For further anabolic polymerisation reaction, it is converted in to glucose-1-phosphate by the reversible action of Phosphoglucomutase . Glucose-1- phosphate is then attached to UTP by the action of UDP-Glucose pyrophosphorylase form UDP-Glucose and pyrophosphate.

7. The C-1 carbon of the glucosyl unit is esterified to the diphosphate group of UDP .. UDP-glucose is the activated form of glucose. It is a high energy compound . It can donate glucose units to the growing glycogen chain. No further energy is required for synthesis of glycogen.

8. Glycogen synthesis by glycogen synthase Glycogen synthase transfers the glucosyl residue from UDP-glucose to the non reducing terminal residues of glycogen. It is transferred to hydroxyl terminal of C4 end of glycogen to form an α-1–4 glycosidic bond. This reaction is catalysed by glycogen synthase. Glycogen synthase is the regulatory enzyme in synthesis of glycogen.

9. UDP-glucose + (glycogen) n residues……………..} UDP +( glycogen) n+1 residues Glycogen synthesis requires a primer. It can add glucosyl residues to the glycogen chain if it contains more than four residues. It means that glycogen synthase can only extend an existing chain. Priming function is carried out by glycogenin .

10. Glycogen Branching Glycogen synthase catalyzes only α- 1–4 glycosidic bonds. It results in to the formation of α- amylose. Branching is catalysed by separate enzyme called Branching enzyme. It is also known as amylo -(1–4→1–6) transglycosylase After a number of glucose units have been linked as a straight chain with α1–4 linkages, branching enzyme breaks α 1–4 bonds.

11. It breaks a 7 unit segment of α 1–4 residues from a glycogen chain and transfers to a C-6 hydroxyl group of a glucosyl residue that is four residues away from an existing branch. Reattachment is done by creating an α1–6 bond . Branches are very important in a growing chain of glycogen. Enzymes involved in glycogen synthesis (glycogen synthase) and degradation (glycogen phosphorylase) works only at the ends of the glycogen molecules . More terminal ends increases the rate of synthesis and degradation of glycogen.

12. GLYCOGENOLYSIS

13. STEPS OF GLYCOGENOLYSIS 1. Glucose-1-phosphate formation from non reducing end of glycogen by Glycogen phosphorylase 2. Removal of α-1,6 branches from glycogen by Glycogen Debranching enzyme 3. Glucose-6-phosphate formation from Glucose-1-phosphate by Phosphoglucomutase .

14. 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 phosphate is referred to as phosphorolysis.

15. Glycogen phosphorylase act on exoglycosidic bond. 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.

16. 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.

17. Glycogen debranching enzyme shows two different activities . Transferase activity and α 1-6 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 ( 1-4 ) linkage and formation of new α ( 1-4) linkage in another branch. This action leaves a single glucose at the α1,6 branch.

18. In α 1-6 glucosidase activity, enzyme removes the single glucose residue which is remaining at branch point by an alpha ( 1-6] 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 1-6 glucosidase activity of the glycogen debranching enzyme.

19. 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 is transferred 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

20. 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 is very important.

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