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1. Metabolism
of glycogen
Karolina Szewczyk-Golec, PhD
Department of Medical Biology and Biochemistry
Collegium Medicum in Bydgoszcz UMK in Toruń
Academic year 2024/2025

2. Function of glycogen
❖ it functions as energy storage in animal cells
❖ glycogen exists in liver and muscle in cytoplasmic granules
that contain enzymes for its synthesis and breakdown
skeletal muscle - ~ 400g glycogen (1-2% weight)
liver - ~ 100g glycogen (6-8% weight)
❖ liver glycogen:
 during well-fed state
 during fasting
❖ muscle glycogen is only moderately
depleted during prolonged fasting

3. Structure of glycogen

4. Glycogenogenesis
❖ to initiate glycogen synthesis, the glucose 6-phosphate is converted
to glucose 1-phosphate by phosphoglucomutase, which catalyzes the
reversible reaction :
❖ the product of this reaction is converted to UDP-glucose by the
action of UDP-glucose pyrophosphorylase, in a key step of
glycogen biosynthesis
❖ pyrophosphate is rapidly hydrolyzed by inorganic pyrophosphatase

5. UDP-glucose pyrophosphorylase

6. Glycogenogenesis

7. Glycogen synthase

8. Synthesis of branches in glycogen
❖ glycogen synthase cannot make the (α1→6) bonds
❖ these bonds are formed by the glycogen-branching enzyme, also
called amylo (1 → 4) to (1 → 6) transglycosylase or glycosyl-(4 →6)
-transferase
❖ the glycogen-branching enzyme catalyzes transfer of a terminal
fragment of 6 or 7 glucose residues from the nonreducing end of a
glycogen branch having at least 11 residues to the C-6 hydroxyl group
of a glucose residue at a more interior position of the same or another
glycogen chain, thus creating a new branch

9. Role of branching
in glycogen
❖ the biological effect of branching is to make the
glycogen molecule more soluble and to increase the
number of nonreducing ends
❖ this increases the number of sites accessible to
glycogen phosphorylase and glycogen synthase, both
of which act only at nonreducing ends

10. Role of glycogenin in glycogen synthesis
❖ glycogen synthase cannot initiate a new glycogen chain de novo
❖ it requires a primer, usually a preformed (1→4) polyglucose
chain or branch having at least eight glucose residues
❖ the protein glycogenin is both the primer on which new chains
are assembled and the enzyme that catalyzes their assembly

11. Role of glycogenin in glycogen synthesis
❖ the first step in the synthesis of a new glycogen molecule is the
transfer of a glucose residue from UDP-glucose to the hydroxyl
group of Tyr194 of glycogenin, catalyzed by the protein’s
intrinsic glucosyltransferase activity
❖ the nascent chain is extended by the sequential addition of
seven more glucose residues, each derived from UDP-glucose
❖ the reactions are catalyzed by the chain-extending activity of
glycogenin
❖ then (when 8-glucose residue chain is ready), glycogen synthase
takes over, further extending the glycogen chain
❖ glycogenin remains buried within the particle, covalently
attached to the single reducing end of the glycogen molecule

12. Glycogenolysis

13. Glycogenolysis
❖ removal of a terminal glucose residue from the nonreducing
end of a glycogen chain is catalysed by glycogen phosphorylase

14. Glycogen phosphorylase
❖ this process is repetitive and the enzyme removes successive glucose
residues until it reaches the fourth glucose unit from a branch point

15. Breakdown od glycogen
near a branch point
(α-[1→4] →α-
[1→4] glucan
transferase)

16. Phosphoglucomutase
❖ glucose 1-phosphate, the end product of the glycogen
phosphorylase reaction, is converted to glucose 6-
phosphate by phosphoglucomutase:
❖ the glucose 6-phosphate formed from glycogen in
skeletal muscle can enter glycolysis and serve as an
energy source to support muscle contraction
❖ in liver, glycogen breakdown serves a different purpose:
to release glucose into the blood when the blood
glucose level drops, as it does between meals
❖ this requires an enzyme, glucose 6-phosphatase, that is
present in liver and kidney but not in other tissues

17. Function of glucose 6-phosphatase in
glycogenolysis in the liver

18. Regulation of glycogen metabolism

19. Glycogen phosphorylase regulation in the liver
❖ in the liver, one of the serine hydroxyl groups of
active phosphorylase a is phosphorylated
❖ it is inactivated by hydrolytic removal of the
phosphate by protein phosphatase-1 to form
phosphorylase b
❖ reactivation requires rephosphorylation catalyzed
by phosphorylase kinase

20. Regulation of liver glycogen metabolism by glucose
❖ glucose binds to and inhibits glycogen phosphorylase a in the
liver, leading to the dissociation and activation of protein
phosphatase 1 (PP1) from glycogen phosphorylase a
❖ the free PP1 dephosphorylates glycogen phosphorylase a and
glycogen synthase b, leading to the inactivation of glycogen
breakdown and the activation of glycogen synthesis

21. Glycogen phosphorylase regulation in muscle
❖ muscle phosphorylase is distinct from that of liver
❖ it is a dimer, each monomer containing 1 mol of PLP
❖ it is present in two forms: phosphorylase a, which is
phosphorylated and active in either the presence or absence
of 5′-AMP (its allosteric modifier) and phosphorylase b,
which is dephosphorylated and active only in the presence of
5′-AMP
❖ this occurs during exercise when the level of 5′-AMP rises,
providing, by this mechanism, fuel for the muscle
❖ phosphorylase a is the normal physiologically active form of
the enzyme

22. Regulation of glycogen metabolism during fasting

23. Second messenger
signaling pathway

24. Second messenger signaling pathway

25. Regulation of glycogen
breakdown

26. Insulin regulation of glycogen metabolism

27. Insulin regulation of carbohydrate metabolism
in the liver

28. Insulin regulation of carbohydrate metabolism
in skeletal muscle

29. Regulation of glycolysis in muscle

30. Glycogen storage diseases in humans

31. Glycogen storage diseases in humans

32. Uronic acid pathway