Glycogenolysis

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Glycogenolysis
.
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Glycogen Metabolism

• Glycogen Degradation Reactions and
  Enzymes Sites of Storage and Use
• Regulation of Glycogen Metabolism- Mechanisms
  of Regulation
• Hormonal Control of Enzymes

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Glycogen Structure
Linkages all a 1-gt4 chains and 1-gt6
branches Branches every 8-12 residues allow
compact, less fibrillar structure and high number
of non-reducing ends
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Most Glycogen is Stored in Liver and Muscle
Liver - 6-8 glycogen, wet weight Muscle -
1-2 glycogen, wet weight
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Glycogen plays different roles in liver and muscle
Liver supplies tissues with Glc from glycogen
during fasting In muscle, conversion of glycogen
to Glc is important during strenuous exercise,
and conversion of Glc to glycogen plays important
role in lowering blood Glc after feeding
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Liver glycogen stores are partially depleted,
even during short fasts
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Depletion of Liver Glycogen over 24 h
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Two major enzymes participate in all glycogen
degradation
Glycogen phosphorylase and Glycogen debranching
enzyme
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Glycogen phosphorylase removes most glucose
residues as Glc-1-P
toward a-1-gt4 linkages from non-reducing ends,
releasing successive Glc-1-P residues, BUT only
to within 4 residues of a branchpoint
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Molecules left after complete phosphorylase
digestion of glycogen are Limit Dextrins
Non-reducing ends
Reducing end
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Glycogen Debranching Enzyme accesses branchpoints
and residues close to branchpoints
The Debranching Enzyme accomplishes this using
two different enzyme activities on the same
polypeptide ?-1,4-gt1,4 Glucan transferase and
?-1,6 Glucosidase
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1. a-1,4-gt1,4 Glucosyl transferase activity
transfers three residues to another chain 2.
Amylo a-1-gt6 Glucosidase- hydrolytic activity
releases Glc
1
2
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Major Final Product of Glycogen Degradation is
Glc-1-P
In muscle, glycogen is degraded to provide an
immediate energy source. Therefore, Glc-6-P is
needed for entry into glycolysis. In liver,
glycogen is a storage form that helps provide Glc
to peripheral tissues in times of low circulating
sugar. Therefore, liver needs to produce free
Glc.
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To Complete Glycogen Degradation, Need to Convert
Glc-1-P to Useful Form
MUSCLE Phosphoglucomutase Glc-1-P
----------------------gt Glc-6-P ----------gt
Glycolysis
LIVER Phosphoglucomutase Glucose-6-Phosphatase
Glc-1-P ------------------------gt Glc-6-P
--------------gt Glucose
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Glycogen Degradation
(red. end)
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Regulation of Glycogen Metabolism
Glycogen synthase and glycogen phosphorylase are
the targets of allosteric modulators and of
covalent, reversible modification
(phosphorylation)
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Glycogen Phosphorylase Regulation
Glycogen phosphorylase is regulated by allosteric
modulators AMP () and Glc, Glc-6-P, ATP
(-) Thus, both energy status and Glc availability
impinge on activity This control is integrated
with regulation by phosphorylation
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Allosteric regulation of phosphorylase activity
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Glycogen phosphorylase is activated by
phosphorylation
Phosphorylase kinase activates glycogen
phosphorylase by phosphorylating one site on each
subunit of the homodimer Phosphorylase a is more
active, and cannot be activated further by AMP
CAN be inhibited by Glc and ATP Phosphorylase b
is less active, and can be activated by AMP
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Phosphorylase Regulation