Glycogen Synthesis and Degradation
 Glycogen is a form of stored glucose which is relatively inert while being
readily mobilised form of glucose.
 It is a very large molecule (up to 120,000 glucose residues per mole) and highly
branched polymer of glucose consisting of mainly -1,4 linked glucose residues with
-1,6-branches every ten residues or so.
 This means that it has one reducing group at the core of the molecule and
hundreds of non-reducing ends per molecule of glycogen where enzymes can act to
add or remove glucosyl units.
 Glycogen is synthesised in times of plenty when glucose is available e.g. after
feeding and mobilised during starvation to keep the blood glucose level constant.
Glycogen Degradation
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Glycogen phosphorylase is the main enzyme involved in glycogen degradation
It catalyses the phosphorolysis of the terminal -1,4 glycosidic linkage at the
non-reducing ends, with the release of glucose 1-phosphate and a glycogen chain
which has been shortened by one glucose residue.
 The -1,6 glycosidic linkages are removed by a debranching enzyme.
 The glucose 1-phosphate is readily converted to glucose 6-phosphate by
phosphoglucomutase and can thus be exported as glucose after hydrolysis by
Glcose-6-phosphatase by the liver or used for glycolysis by the muscle.
Glu-1-P
>
Glu-1,6-P2
>
Glu-6-P
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Glycogen degradation to glucose 6-phosphate is a readily reversible set of
reactions in theory, but in vivo the reaction proceeds in the direction of glycogen
breakdown because of the excess of Pi compared to Glucose 1-phosphate.
Glycogen Synthesis

In contrast to glycogen degradation, the synthesis is an energy requiring
pathway which is distinct from allowing for the reciprocal control of the synthesis and
degradation.
 Synthetic pathway involves a high-energy intermediate UDP-glucose, which
acts as a glucosyl donor for the synthesis of glycogen.
 UDP-glucose is synthesised from UTP and Glucose 1-phosphate by the enzyme
UDP-glucose pyrophosphorylase and pyrophosphate (PPi) is also produced. This
reaction is readily reversible.
UTP
+
Glu-1-P

UDP-Glu
+
PPi
 The pathway is essentially irreversible due to the hydrolysis of PPi by a very
active pyrophosphatase.
 Many biosynthetic reactions are driven by the hydrolysis of PPi.
 Glycogen Synthase catalyses the transfer of glucose from UDP-Glu to the nonreducing ends of the glycogen molecule.
 Glucosyl unit is transferred to the C-4 in the terminal glucose residue to form an
-1,4 glycosidic linkage.
 Branching enzyme (a different protein to debranching enzyme) breaks an 1,4 glycosidic and transfers the resultant oligosaccharide which is then attached via an
-1,6 glycosidic linkages at regular intervals in the glycogen.
 Branches are created by transferring blocks of 7 glucosyl residues to the C6
hydroxyl of a glucose unit in an adjacent chain.
 Each oligosaccharide block of 7 residues must come from a linear chain of at
least 11 -1,4 glucosyl residues and the new branch point must be at least 4 residues
away from another branch point
 In plant starch (amylopectin) which has a comparable structure to glycogen,
although with fewer branch points, ADP-glucose is the main high energy glucosyl
donor.
Glycogenin
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BS2510 -2004
In a number of purification schemes for the isolation of glycogen synthase (86
kDa) from muscle it has proved very difficult to separate a tightly bound
contaminating protein which forms a 1:1 mole/mole complex with GS
It turned out that this protein (Glycogenin) had an important function in the
initiation of glycogen synthase
It has glycogen synthase –like activity and is capable of auto-glycosylation,
the transfer of Glucose from UDP-Glu to a Tyr194 residue within the protein
Glycogenin then transfers a further 7 Glucosyl residues
The reactions are autocatalytic (ie catalysed by glycogenin itself) until the
oligosaccharide grows to 8 units at which point Glycogen Synthase and
Branching Enzyme take over
The glycogenin remains buried at the core of each glycogen molecule.
Glycogen Synthase is incapable of de novo glycogen synthesis
Muscle glycogenin can be distinguished from Glycogen Synthase because of
the different MWt, a higher affinity for UDP-Glu,and the fact that it requires
Mn2+ for activity
Now cloned and expressed in E.Coli and shown to be capable of
autoglycosylation and the initiation of glycogen synthesis
Two forms of glycogenin have been found in mammalian systems
o Glycogenin 1 (37 kDa form with a broad tissue distribution, inc.
muscle)
o Glycogenin 2 (50 – 55 kDa in liver, pancreas and heart)