Glycogenolysis

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. These slides will provide you detail explanation of Glycogenolysis.

1. GLYCOGENOLYSIS
ANUP MUNI BAJRACHARYA

2. GLYCOGENOLYSIS
process to break the glycogen down into individual
glucose molecules is calledglycogenolysis.
process by whichglycogen, 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.
Glycogenolysisoccurs primarily in the liver and is
stimulated by the hormone glucagon and epinephrine
(adrenaline).

3. WHAT IS GLYCOGEN?
Glycogen is the major storage form of
carbohydrate in animals.
It is a homopolymermade up of repeated units
of α-D glucose and each molecule is linked to
another by 1→4 glycosidicbond.

4. STEPS IN GLYCOGENOLYSIS
Glycosyl4:4 transferase
(oligoα-1,4→1,4 glucan
transferase)

5. STEP 1: ACTION OF GLYCOGEN PHOSPHORYLASE
Thealpha-1,4-glycosidic bonds(from non-reducing ends) are
cleaved sequentially by the enzymeGlycogen Phosphorylaseto
yield glucose 1-phosphate.
This process is called Phosphorolysiscontinues until four
glucose residues remain on either side of the branching point
(alpha-1,6-glycosidic bond).
At first step of glycogenolysis,glycogen phosphorylasecleaves
the α(1→4) linkages of glycogen to form glucose 1-phosphate.

7. STEP 2: ACTION OF DEBRANCHING ENZYME
The branches of Glycogen are cleaved by two enzyme activities
present on a single polypeptide called adebranching
enzyme,hence it is abifunctionalenzyme.
Glycosyl4:4 transferase(oligoalpha 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.
Amyloalpha-1,6-glucosidasebreaks the alpha-1,6-bond at the
branch with a single glucose residue.

8. From the outermost chains of
glycogen molecule, the terminal
glucosylresidues 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
transferaseor α(1→4)
transglycosylase
and
amylo-α(1→6)-glucosidase.

10. STEP 3: FORMATION OF GLUCOSE -6-PHOSPHATE
AND GLUCOSE
Through the combined action of Glycogen phosphorylaseand
debranchingenzyme, glucose-1-phosphate and free glucose in a ratio of
8:1 are produced.
Glucose-1-Phosphate is converted toGlucose-6-phosphateby the
enzymePhosphoglucomutase.
Finally, in liver, but not in skeletal muscle,glucose 6-
phosphataseenzyme hydrolyzes glucose 6-phosphate, forming glucose
that is exported to circulation, leading to an increase blood glucose.

12. FATE OF GLUCOSE -6-PHOSPHATE
The fate of Glucose-6-Phosphate is…
InLiver, Kidney,andIntestine(haveGlc-6-Phosphatase) Glc-
6-P is cleaved into Glucose. The enzyme is absent
inMuscleandBrain
InPeripheral tissues, Glc-6-P will be used for Glycolysis.
Glycogenolysisis inhibited byfructose-1-phosphate at the
level of phosphorylase

13. REGULATION OF GLYCOGENOLYSIS
Regulation of glycogenolysisis accomplished on two levels
such as
allosteric regulation and
hormonal regulation.

14. ALLOSTERIC REGULATION
1)In fasting state→glycogen phosphorylaseis allostericallyactivated
by glucose 6-phosphate and ATP (in liver, not in muscle, free glucose is
also an activator)→glycogenolysis.
In contrast,glycogen synthase is allostericallyinhibited 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→stimulatesglycogen
phosphorylase→glycogenolysis.
3)In muscle under extreme conditions of anoxia and ATP
depletion→increase AMP level in muscle→stimulatesglycogen
phosphorylase→glycogenolysis.

15. HORMONAL REGULATION
1) Glucagon and epinephrine –Glucagon and epinephrine
stimulate glycogenolysisby stimulatingGlycogen
phosphorylaseenzyme activity.
2) Insulin –Insulin inhibits glycogenolysisby
inhibitingGlycogen phosphorylaseenzyme activity.

16. SIGNIFICANCE
Glycogenolysisplays an important role in thefight-or-flight
response.
It contributes to the regulation of glucose levels in the blood.
The metabolism ofglycogenpolymers becomes important
during fasting.
Inmyocytes(muscle cells), glycogen degradation serves to
provide an immediate source of glucose-6-phosphate
forglycolysis, to provide energy for muscle contraction.
Inhepatocytes), the main purpose of the breakdown of
glycogen is for the release of glucose into the bloodstream
for uptake by other cells.

17. A.B