Glycogenolysis

GLYCOGENOLYSIS
Glycogen breakdown
2 GLYCOSIDIC LINKAGES
Glycogen Storage
Degradtion Of stored Glycogen
Phosphorolysis
Glycogen breakdown by glycogen phosphorylase
Debranching enzyme
Glycosyl 4:4 transferase (oligo α-1,4→1,4 glucan transferase)
Amylo α-1-6-glucosidase
Bifunctional enzyme
Glycogen Debranching Enzyme
formation of free glucose and glucose-6-phosphate
Glucose Metabolism in Liver
Regulation Of Glycogenolysis
1.Allosteric regulation
2. Hormonal regulation
3. Influence of calcium

1. GLYCOGENOLYSIS

2. Gul Muneer 23 Ghulam Mujtaba 102Fawad Ahmed 20
Sultan Ali 77
Lal malook 38
Abdul Qadir 01
Hifz-ur-Rahman 28Mohammad Junaid 50
Asad Ali 10
Group E
B.S Part-III
B.S Part-III Institute of Biochemistry

3. GLYCOGEN OVERVIEW
 Homopolysaccharide
 Homopolymer of α-D-glucose
 Highly branched

4. 2 GLYCOSIDIC
LINKAGES
 Linear linkages α(1→4)
 Branching linkages α(1→6)
 Branches after once every
8-10 residues
 Linear 13 glucose residues
 Branches 12 glucose residues

5. Storage
 Storage form of Glucose in animals
 So called “animal starch”
 Granular form
 High in liver (6-8%) and muscles
(1-2%)
 Liver
 regulates blood glucose levels
Muscle
Store of glucose as fuel for exercise
 high intensity exercise dependent on
anaerobic glycolysis

6. Glycogenolysis
Degradtion Of stored Glycogen
occurs in cytosol
triggered by low blood glucose levels
why this pathway occurs?
=When an organism needs energy quickly
=During muscular exercise
=can do so anaerobically

7. 1st Step
Phosphorolysis
Enzyme: Glycogen phosphorylase
Action: Cleavage of α(1→4)linkages
Position: non-reducing ends
Coenzyme: Pyridoxal phosphate (vit.B6 derivative)
Product: glucose-1-phosphate
Limits: degrades the Glycogen molecule until 4 glucose residues
remain on each chin before a branch point.
( Stops at 4 Glucose residue)
Result: Limit dextrin
NOTE: This cannot further degraded by phosphorylase
Inhibitor: a suitable treatment for diabetes (liver phosphorylase)

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9. 2nd Step
Removal of Branches
General name: Debranching enzyme

Structure:
=2 independent active site
=Single polypeptide cleaves branches by 2
enzyme activities (Bifunctional enzyme)
Two enzyme activities:
●
Glycosyl 4:4 transferase (oligo α-1,4→1,4 glucan transferase)
●
Amylo α-1-6-glucosidase

10. glycosyl 4:4 transferase:
 Removes chain of (3 or 4) glucose residue at a branch
 Transfer them to the non-reducing end of another chain
 α-1,4 bond is broken and α-1,4 bond is made.
amylo -1,4 glucosidase:
α
 Breaks the α-1,6 bond at branch point
 Action is hydrolytically
 Releases a free glucose
 Skeletal muscle do generate free glucose that could enter
bloodstream
 Hexokinase ―low Km (immediately phosphorylate)

11. Glycogen
Debranchin
g Enzyme
a-(1—>4) transglycosylase
Glucosea-(1—>6) glucosidase
Limit Branch (4 residues)
(group transfer reaction)

12. The remaining molecule of glycogen is
again available for the action of
phosphorylase and debranching enzyme to
repeat the reactions stated in 1 and 2.

13. 3rd step
formation of free glucose and glucose-6-phosphate
●
catalysed by phosphoglucomutase
●
product fate depends on tissue

14. Glucose-6-phosphate may enter Glycolysis or (mainly in
liver) be dephosphorylated for release to the blood.
Liver Glucose-6-phosphatase catalyzes the following,
essential to the liver's role in maintaining blood glucose:
glucose-6-phosphate + H2O  glucose + Pi
Most other tissues lack this enzyme.

Glycogen Glucose
Hexokinase or Glucokinase
Glucose-6-Pase
Glucose-1-P Glucose-6-P Glucose + Pi
Glycolysis
Pathway
Pyruvate
Glucose metabolism in liver.

15. Regulation Of
Glycogenolysis
Glycogenolysis is controlled by enzyme glycogen
phophorylase
Regulation of this enzyme is accompalished by 3
mechanisms:
1.Allosteric regulation
2. Hormonal regulation
3. Influence of calcium

16. Allosteric regulation
Glycogen breakdown is enhanced:
●
low glucose conc
●
low energy level
 glycogen breakdown inhibited:
●
high Glucose-6-phosphate
●
ATP
●
Free glucose in liver
●
Above metabolites allosterically regulate glycogen
phosphorylase.

17. Hormonal And Ca²
⁺
Regulation

18. Hormonal Regulation
Low blood glucose level (fasting)
Releases these 2 hormones
Glucagon
Epinephrine
Glucogen phosphorylase
exists in 2 forms:
1. An active “a” form
2. An inactive “b” form
Glucagon and epinephrine both
stimulate intracellular pathway via
increasing levels
of cAMP.

19. Ca²⁺ Ions Influence
Ca²⁺ regulates
glycogen breakdown
in muscle.
Release of Ca²⁺
from ER into cytosol
of muscle cells
causes muscle
contraction resulting
urgent need of ATP.

20. Thank you