This document discusses glycogen metabolism. It notes that glycogen is a readily available form of glucose storage found primarily in the liver and muscles. Glycogen synthesis, or glycogenesis, occurs in the fed state in these tissues and involves three steps - isomerization of glucose-6-phosphate to glucose-1-phosphate, activation of glucose-1-phosphate to UDP-glucose, and linkage of UDP-glucose to a glycogen chain catalyzed by glycogen synthase. Glycogen branching is accomplished by the enzyme amylo-(1,4-1,6)-trans-glycosylase which transfers glycogen segments to form branches. The synthesis and breakdown of glycogen in the liver and muscles

1. Glycogen Metabolism
Dr. Usman Saleem
Rashid Latif College of Pharmacy

2. Glycogen
An Overview
•Glycogen is a readily mobilized storage form of glucose.
•It is a branched chain polymer of glucose in which
glucose units are linked to each other through a-1,4 and
a-1,6 linkages.
•The bulk of glycogen is stored in liver and muscles.

3. Glycogen
Storage Site and Functions
• The bulk of glycogen is stored in liver and muscles.
• In liver – The synthesis and breakdown of glycogen is
regulated to maintain blood glucose levels.
• In muscle - The synthesis and breakdown of glycogen is
regulated to meet the energy requirements of the muscle
cell.

4. Glycogen Metabolism-Glycogenesis and Glycogenolysis

5. Glycogen Synthesis
(Glycogenesis)
•Glycogenesis is the metabolic pathway by which glycogen
is synthesized from glucose 6-phosphate.
•It occurs in liver and muscles in fed state.
•Glycogenesis involves three reactions (steps).

6. Step-1: Isomerization
(Formation of Glucose 1-phosphate)
•The starting material for this step is not glucose itself but
rather glucose 6-phosphate (available from the first step
of glycolysis).
•Glucose-6-phophaste is converted to Glucose-1-
phosphate by the enzyme phosphoglucomutase.

7. Step-1: Isomerization
(Formation of Glucose 1-phosphate)

8. Step-2: Activation
(Formation of UDP-Glucose)
•Glucose-1-phosphate reacts with uridine triphosphate
(UTP) to form uridine diphosphate glucose (UDPG) and
pyrophosphate (PPi).
•The reaction is catalyzed by the enzyme UDP-glucose
pyrophosphorylase.

10. Step-3: Linkage to the Chain
(GlucoseTransfer to a Glycogen Chain)
•The activated glucose unit of UDP-glucose is then
transferred to pre-existing glycogen molecule (the
glycogen primer), liberating uridine diphosphate (UDP).
•The enzyme glycogen synthase catalyze this reaction by
forming new a-1,4 glycosidic linkage and lengthens the
chain.

11. Step-3: Linkage to the Chain
(GlucoseTransfer to a Glycogen Chain)

12. Step-3: Linkage to the Chain
(GlucoseTransfer to a Glycogen Chain)
•In a subsequent reaction, the UDP produced is converted
back to UTP, which can then react with another glucose
1-phosphate.

13. Step-3: Linkage to the Chain
(GlucoseTransfer to a Glycogen Chain)
• Synthesis of glycogen requires a pre-existing glycogen or a
primer molecule.
• Glycogen primer can be synthesized on the backbone of a
protein called glycogenin.
• The glycogenin molecule itself acts as the catalyst for addition of
glucoses until there are about eight of them linked together.
• At that point, glycogen synthase take over.

14. Glycogen Branching
• Synthesis of glycogen requires the formation of a (1,6) as well as
a (1,4) glycosidic linkages.
• This task is accomplished by “branching enzyme” called amylo
(1,4-1,6)-trans-glycosylase.
• Branching enzymes catalyze the transfer of a segment containing 6 or
7 residues—from a chain containing at least 11 residues—to some
place on the same chain or on a different chain.

15. Glycogen Branching

16. Thanks