GLYCOGENOLYSIS

ANUP MUNI BAJRACHARYA

 GLYCOGENOLYSIS
process to break the glycogen down into individual
glucose molecules is called glycogenolysis.

process by which glycogen, the primary carbohydrate

stored in the liver and muscle cells of animals, is
broken down into glucose to provide immediate energy
and to maintain blood glucose levels during fasting.

Glycogenolysis occurs primarily in the liver and is

stimulated by the hormone glucagon and epinephrine
(adrenaline).
 WHAT IS GLYCOGEN?

Glycogen is the major storage form of

carbohydrate in animals.
It is a homopolymer made up of repeated units
of α- D glucose and each molecule is linked to
another by 1→4 glycosidic bond.
STEPS IN GLYCOGENOLYSIS

Glycosyl 4:4 transferase

(oligo α-1,4→1,4 glucan
transferase)
STEP 1: ACTION OF GLYCOGEN PHOSPHORYLASE

The alpha-1,4-glycosidic bonds (from non-reducing ends) are

cleaved sequentially by the enzyme Glycogen Phosphorylase to
yield glucose 1-phosphate.

This process is called Phosphorolysis continues until four

glucose residues remain on either side of the branching point
(alpha-1,6-glycosidic bond).

At first step of glycogenolysis, glycogen phosphorylase cleaves

the α(1→4) linkages of glycogen to form glucose 1-phosphate.
STEP 2: ACTION OF DEBRANCHING ENZYME

The branches of Glycogen are cleaved by two enzyme activities

present on a single polypeptide called a debranching
enzyme, hence it is a bifunctional enzyme.

Glycosyl 4:4 transferase (oligo alpha 1,4—>1,4 glucan

transferase) activity removes a fragment of three or four Glucose
residues attached at a branch and transfers them to another
chain.
Here, one alpha-1,4-bond is cleaved and the same alpha-1,4 bond
is made, but the places are different.

Amylo alpha-1,6-glucosidase breaks the alpha-1,6-bond at the

branch with a single glucose residue.
From the outermost chains of
glycogen molecule, the terminal
glucosyl residues are detached
sequentially until approximately
four glucose residues remain
on either side of an α(1→6)
branch.

Branches of glycogen are

removed by two debranching
enzymes such as

α(1→4) →α(1→4)-glucan
transferase or α(1→4)
transglycosylase

and

amylo- α(1→6)-glucosidase.
STEP 3: FORMATION OF GLUCOSE-6-PHOSPHATE
AND GLUCOSE

Through the combined action of Glycogen phosphorylase and

debranching enzyme, glucose-1-phosphate and free glucose in a ratio of
8:1 are produced.

Glucose-1-Phosphate is converted to Glucose-6-phosphate by the

enzyme Phosphoglucomutase.

Finally, in liver, but not in skeletal muscle, glucose 6-

phosphatase enzyme hydrolyzes glucose 6-phosphate, forming glucose
that is exported to circulation, leading to an increase blood glucose.
FATE OF GLUCOSE-6-PHOSPHATE
The fate of Glucose-6-Phosphate is…
In Liver, Kidney, and Intestine (have Glc-6-Phosphatase) Glc-
6-P is cleaved into Glucose. The enzyme is absent
in Muscle and Brain

In Peripheral tissues, Glc-6-P will be used for Glycolysis.

Glycogenolysis is inhibited by fructose-1-phosphate at the

level of phosphorylase
 REGULATION OF GLYCOGENOLYSIS
Regulation of glycogenolysis is accomplished on two levels
such as
allosteric regulation and
hormonal regulation.
ALLOSTERIC REGULATION

1) In fasting state → glycogen phosphorylase is allosterically activated

by glucose 6-phosphate and ATP (in liver, not in muscle, free glucose is
also an activator) → glycogenolysis.
In contrast, glycogen synthase is allosterically inhibited by glucose 6-
phosphate and ATP → no glycogenolysis

2) During muscle contraction → membrane depolarization occurs by

nerve impulses → increase calcium concentration in muscle
cell → calcium binds with calmodulin → stimulates glycogen
phosphorylase → glycogenolysis.

3) In muscle under extreme conditions of anoxia and ATP

depletion → increase AMP level in muscle → stimulates glycogen
phosphorylase → glycogenolysis.
HORMONAL REGULATION

1) Glucagon and epinephrine – Glucagon and epinephrine

stimulate glycogenolysis by stimulating Glycogen
phosphorylase enzyme activity.
2) Insulin – Insulin inhibits glycogenolysis by
inhibiting Glycogen phosphorylase enzyme activity.
SIGNIFICANCE
Glycogenolysis plays an important role in the fight-or-flight
response.
It contributes to the regulation of glucose levels in the blood.
The metabolism of glycogen polymers becomes important
during fasting.
In myocytes (muscle cells), glycogen degradation serves to
provide an immediate source of glucose-6-phosphate
for glycolysis, to provide energy for muscle contraction.
In hepatocytes), the main purpose of the breakdown of
glycogen is for the release of glucose into the bloodstream
for uptake by other cells.
A.B