sign in sign up
<<
Home , Glycogenolysis, Phosphoglucomutase

Paper : 04 of

Module : 24

Dr. Vijaya Khader Dr. MC Varadaraj

Dr.S.K.Khare,Professor Principal Investigator IIT Delhi.

Dr. Ramesh Kothari,Professor Paper Coordinator UGC-CAS Department of Biosciences Saurashtra University, Rajkot-5, Gujarat-INDIA

Dr. S. P. SinghProfessor Content Reviewer UGC-CAS Department of Biosciences Saurashtra University, Rajkot-5, Gujarat-INDIA

Content Writer Dr.VikramRaval,Assistant Professor UGC-CAS Department of Biosciences Saurashtra University, Rajkot-5, Gujarat-INDIA

1

Metabolism of Carbohydrates Biochemistry Glycogenolysis

Description of Module

Subject Name Biochemistry

Paper Name 04 Metabolism of carbohydrates

Module Name/Title 24 Glycogenolysis

2

Metabolism of Carbohydrates Biochemistry Glycogenolysis

GLYCOGENOLYSIS

Objectives

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

3

Metabolism of Carbohydrates Biochemistry Glycogenolysis

Introduction

. The biological degradation of glycogen is termed as glycogenolysis. . Glycogen is a highly branched, large of 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 and regulatory which is required for its synthesis and degradation.It acts as an important energy reserve for the body. It is stored in the and .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 and glycogenolysis is very important in maintaining the glycogen . These two processes are commonly regulated. Hormones which stimulate glycogenolysis (e.g. , , , nor

4

Metabolism of Carbohydrates Biochemistry Glycogenolysis

epinephrine) concurrently inhibit glycogenesis. On the other hand, , 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 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.

GLYCOGEN

GLUCOSE

Fig: 24.1 Glycogenolysis leads to formation of glucose

STEPS OF GLYCOGENOLYSIS

Glycogenolysis requires2main enzymes. Glycogenolysisoccurs by a different pathwayfrom glycogenesis.

5

Metabolism of Carbohydrates Biochemistry Glycogenolysis

1. Glucose-1- 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-phosphateby .

GLYCOGEN (n residues) Pi Glycogen phosphorylase GLYCOGEN (n-1 residues)

GLUCOSE-1-PHOSPHATE

Phosphoglucomutase

GLUCOSE-6-PHOSPHATE

Glucose-6-Phosphatase

(In liver) GLUCOSE

Diffuse in to the bloodstream

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 6

Metabolism of Carbohydrates Biochemistry Glycogenolysis

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 reaction also involves the same process but it uses water instead of phosphate for the cleavage of bond.

GLYCOGEN (n residues)

HPO4-2 GLYCOGEN PHOSPHORYLASE

GLYCOGEN (n-1)

. Cleavage by phosphorolysisFig: 24.3 Formation is energetically of G- 1favourable-P from glycogen because released glucose is phosphorylated. While hydrolytically release of sugar needs to be phosphorylated before enters into the glycolytic pathway.

7

Metabolism of Carbohydrates Biochemistry Glycogenolysis

. Glycogen phosphorylase act on exoglycosidic bond. is an necessary in the glycogen phosphorylase reaction. This cofactor is linked to 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 differentactivities. o activity o 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

8

Metabolism of Carbohydrates Biochemistry Glycogenolysis

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. . 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.

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

. Glucose-1-phosphate is converted to Glucose-6-phosphate by Phosphoglucomutase. . of the active Phosphoglucomutase molecule has a phosphorylated residue. The phosphoryl group istransferred from the 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 9

Metabolism of Carbohydrates Biochemistry Glycogenolysis

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.

GLUCOSE-1-PHOSPHATE Phosphoglucomutase

(Phosphoryl group from serine residue transferred to G-1-P) GLUCOSE-1-6-BISPHOSPHATE

Phosphoglucomutase

(Phosphoryl group from G-1-6-P transferred to serine residue GLUCOSE-6-PHOSPHATE of enzyme)

Fig: 24.4 Formation of G-6-P from G-1-P

10

Metabolism of Carbohydrates Biochemistry Glycogenolysis