2. • (B1 3.4)Define and differentiate the pathway of glycogen metabolism
• Learning objectives
• Describe the overall purpose of glycogenolysis, their reactants and
products, their cellular localization, and their tissue distribution.
• Describe the roles of enzymes in glycogenesis and glycogenolysis and
discuss their regulation
3.
4. Glycogenolysis
• Breakdown of glycogen in liver and muscle
• Both glycogenolysis and glycogenesis are not reversible
• Site- Cytosol
5. Glycogen phosphorylase
• Rate limiting enzyme of glycogenolysis
• Breaks the α 1-4 glycosidic linkage from the non-reducing end
• This continues till four glucose residues remain on either side of
branching point
• This is known as phosphorylysis
• The glucose molecules are liberated as glucose 1 phosphate
• The glycogen now is known as Limit Dextrin
• Phosphorylase enzyme cannot act on Limit dextrin
6. • Phosphorylase enzyme is present in liver and muscle
• It exists in active and inactive forms
• Liver phosphorylase exists as-
• Active form- as phosphorylated form
• Inactive form- as dephosphorylated form
• Muscle phosphorylase exists as-
• Active form which is a tetramer
• Inactive form which is a dimer
7. Action of de-branching enzyme
• When four glucose residues are left on either side of the branch point
A. Enzyme α 1-4-- α 1-4 Glucan transferase transfers a trisaccharide
unit from one side to another, thus exposing α 1-6 branch point
( can be understood from a diagram in next slide)
B. Enzyme α Amylo 1-6 glucosidae ( another debranching enzyme) is
responsible for splitting of α 1-6 glycosidic linkage
• It is associated with release of free glucose molecule
• The remaining glucose molecule is available for the action of
phosphorylase and debranching enzyme to repeat the above actions
8.
9. • Fate of glucose 1 phosphate- It is converted to glucose 6 phosphate by
phosphoglucomutase
• Glucose 6 phosphate is converted to glucose by Glucose 6 phosphatase
• Glucose 6 phosphatase is present in Liver, kidney and intestine
• It helps in the release of free glucose from glucose 6 phosphate which can
diffuse from cells into extracellular space including blood
• It helps in raising blood glucose levels
• Glucose 6 phosphatase is absent in muscle and brain
• So, glucose 6 phosphate in muscle enters glycolysis and forms pyruvate &
lactate
10. Important points
• So, Muscle glycogenolysis cannot contribute directly to blood glucose
directly
• But indirectly, lactate can contribute to the formation of glucose in
the liver
11.
12.
13.
14. Regulation of glycogenesis & Glycogenolysis
• The rate limiting enzyme of glycogenesis is Glycogen synthase
• The rate limiting enzyme of glycogenolysis is Glycogen phosphorylase
• Allosteric regulation
• Hormonal regulation
• Influence of calcium ions
15. Allosteric regulation of glycogenesis &
Glycogenolysis
• In a well fed state, availability of glucose 6 phosphate is high which
activates glycogen synthase ( ---- enzyme of glycogen synthesis)
• Glycogen breakdown is increased when concentration of glucose and
energy levels are low