Paper : 04 Metabolism of carbohydrates

Module : 24 Glycogenolysis

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
UGC-CAS Department of Biosciences
Content Reviewer
Saurashtra University, Rajkot-5, Gujarat-INDIA

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

Metabolism of Carbohydrates
Biochemistry
Glycogenolysis
 Description of Module

Subject Name Biochemistry

Paper Name 04 Metabolism of carbohydrates

Module Name/Title 24 Glycogenolysis

Metabolism of Carbohydrates
Biochemistry
Glycogenolysis
 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

Metabolism of Carbohydrates
Biochemistry
Glycogenolysis
 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, nor

Metabolism of Carbohydrates
Biochemistry
Glycogenolysis
 epinephrine) 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.

GLYCOGEN

GLUCOSE

Fig: 24.1 Glycogenolysis leads to formation of glucose

STEPS OF GLYCOGENOLYSIS

Glycogenolysis requires2main enzymes. Glycogenolysisoccurs by a different pathwayfrom

glycogenesis.

Metabolism of Carbohydrates
Biochemistry
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-phosphateby
Phosphoglucomutase.

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

GLUCOSE-1-PHOSPHATE

Phosphoglucomutase

GLUCOSE-6-PHOSPHATE

Gl ucose-6-Phospha tase

(In li ver)
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 hydrolysis 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 phosphorolysis is energetically

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

Metabolism of Carbohydrates
Biochemistry
Glycogenolysis
  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 differentactivities.

o Transferase 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

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.
 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
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

of enzyme)
GLUCOSE-6-PHOSPHATE

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

10

Metabolism of Carbohydrates
Biochemistry
Glycogenolysis