Download - 1 glycogenolysis
Glycogenolysis
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Glycogen Metabolism
•Glycogen DegradationReactions and EnzymesSites of Storage and Use
•Regulation of Glycogen Metabolism-Mechanisms of Regulation
Hormonal Control of Enzymes
Glycogen Structure
Linkages all a; 1->4 chains and 1->6 branches
Branches every 8-12 residues allow compact, less fibrillar structure and high number of non-reducing ends
Most Glycogen is Stored in Liver and Muscle
Liver - 6-8% glycogen, wet weight
Muscle - 1-2% glycogen, wet weight
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
Liver glycogen stores are partially depleted, even during
short fasts
Depletion of Liver Glycogen over 24 h
Two major enzymes participate in all glycogen
degradation:
Glycogen phosphorylase
and
Glycogen debranching enzyme
Glycogen phosphorylase removes most glucose residues
as Glc-1-P
toward -1->4 linkages
from non-reducing ends, releasing successive Glc-1-P residues,
BUT only to within 4 residues of a branchpoint
Molecules left after complete phosphorylase digestion of glycogen are
Limit Dextrins
Non-reducing ends
Reducing end
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->1,4 Glucan transferase and
1,6 Glucosidase
-1,4->1,4 Glucosyl transferase activity transfers three residues to another chain
2. Amylo -1->6 Glucosidase- hydrolytic activity releases Glc
1
2
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.
To Complete Glycogen Degradation, Need to
Convert Glc-1-P to Useful Form
MUSCLE:
Phosphoglucomutase
Glc-1-P ----------------------> Glc-6-P ----------> Glycolysis
LIVER:
Phosphoglucomutase Glucose-6-Phosphatase
Glc-1-P ------------------------> Glc-6-P --------------> Glucose
Glycogen Degradation
(red. end)
Regulation of Glycogen Metabolism
Glycogen synthase and glycogen phosphorylase are the targets of allosteric modulators and of covalent, reversible modification (phosphorylation)
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
Allosteric regulation of phosphorylase activity
Glycogen phosphorylase is activated by
phosphorylationPhosphorylase 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
Phosphorylase Regulation