Term
Two enzymes participate in all glycogen degradation |
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Definition
Glycogen phosphorylase
AND
Glycogen debranching enzyme
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Term
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Definition
-removes glucose residues as Glc-1-P
•Glycogen phosphorylase catalyzes phosphorolysis of a-1->4 linkages
•Degradation by phosphorylase is from non-reducing ends, releasing successive Glc-1-P residues BUT only to 4 residues from a branchpoint
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Term
Glycogen Debranching Enzyme |
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Definition
-Accesses Branchpoints and Residues Close to Branchpoints
-Glycogen Debranching Enzyme has two different catalytic centers on the same polypeptide:
oligo a-1,4 -> 1,4 glucosyl transferase activity
AND
amylo a-1,6 glucosidase activity
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Term
a-1,4 Glucosyl transferase |
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Definition
-activity transfers several residues from a limit branch to a different chain |
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Term
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Definition
-hydrolytic activity releases Glc from branchpoints
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Term
Major Product of Glycogen Degradation |
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Definition
-Glc-1-P
-Branchpoint Glc residues make up only 10% of Glc released from glycogen- 90% 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 the peripheral tissues in times of low circulating sugar. Therefore need to produce Glc in liver for export.
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Term
Phosphoglucomutase and Glc-6-Phosphatase in Glycogen Degradation |
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Definition
-convert the major product of glycogenolysis to usable forms for specific tissues |
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Term
Regulation of Glycogen Metabolism |
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Definition
-Glycogen metabolism is regulated by opposite and coordinate control of glycogen synthase and glycogen phosphorylase.
-Glycogen synthase and glycogen phosphorylase both are the targets of allosteric modulators and of reversible covalent modification (phosphorylation)
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Term
Glycogen Phosphorylase Regulation |
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Definition
Glycogen phosphorylase is regulated by binding of allosteric modulators:
AMP (+) and Glc, Glc-6-P, ATP (-)
Thus, both energy status and Glc availability impinge on activity (need for more glucose or need to store glucose).
This direct metabolic regulation is integrated with regulation by phosphorylation (hormonal regulation).
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Term
Glycogen phosphorylase is activated by phosphorylation |
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Definition
Phosphorylase kinase activates glycogen phosphorylase by phosphorylating one site on each subunit of the homodimer
Phosphorylase a (PHOSPHORYLATED) is more active, and CANNOT be activated further by AMP; CAN be inhibited by Glc and ATP
Phosphorylase b (UNPHOSPHORYLATED) is less active, and can be activated by AMP
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Term
Phosphorylase kinase is a complex, multi-subunit enzyme |
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Definition
Phosphorylase kinase g is the catalytic subunit; a, b, and d are regulatory subunits
Phosphorylation of phosphorylase kinase a and b subunits activates the enzyme towards phosphorylase
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Term
Phosphorylase kinase is activated in response to increased cAMP |
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Definition
•cAMP is a second messenger produced in response to some hormonal signals.
•cAMP activates a protein kinase, PKA, that phosphorylates regulatory subunits of phosphorylase kinase.
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Term
cAMP-Dependent Protein Kinase |
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Definition
•cAMP binds to the regulatory subunits (R) of cAMP dependent protein kinase (cAPK or PKA) to cause dissociation of active catalytic monomers (C).
•Intracellular cAMP concentration determines the fraction of active PKA, and thus the rate of substrate phosphorylation.
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Term
Phosphorylase kinase also is activated by Ca2+ |
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Definition
Calmodulin, a regulatory protein that responds to increased cellular Ca2+, is the d subunit of phosphorylase kinase
Binding of Ca2+ to phosphorylase kinase d results in activation of phosphorylase kinase, whether or not a and b subunits are phosphorylated (maximal activation requires both)
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Term
Protein Phosphatase Type 1 |
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Definition
-Dephosphorylates Glycogen Phosphorylase and Phosphorylase Kinase
Regulation in Muscle
•PP1 is associated with the glycogen particle by binding of its glycogen-specific regulatory subunit (GM or GL)
•Muscle PP1 activity is turned down by PKA phosphorylation and turned up by dephosphorylation
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Term
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Definition
-PP1 regulation depends mainly on its ability to bind glycogen phosphorylase
-PP1 is sequestered by active, phosphorylated glycogen phosphorylase; hormonal and metabolic signals can result in dephosphorylation of phosphorylase and release of active PP1 |
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Term
Glycogen Synthase is Regulated in Coordination with Phosphorylase |
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Definition
To avoid futile cycling, glycogen synthase is regulated opposite to phosphorylase
Remember, glycogen synthase also is regulated by BOTH allosteric modulation (Glc-6-P) and phosphorylation (by numerous kinases)
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Term
Allosteric activation of Glycogen Synthase by Glc-6-P |
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Definition
Allosteric activation is integrated with negative regulation by phosphorylation
-Glc-6-P is required for activity of the phosphorylated, less active, synthase protein and appears to promote dephosphorylation
*Glc-6-P does not activate the unphosphorylated form further
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Term
Phosphorylation by several different protein kinases inhibits glycogen synthase |
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Definition
•Glycogen synthase can be phosphorylated on at least 9 sites by at least 11 different protein kinases (PKA, PKC, GSK, CKI, CKII, etc.), all of which decrease activity
•Phosphorylation at different sites decreases activity by different increments- rheostat-like
•Kinases acting on glycogen synthase respond to many signals, including cAMP and Ca2+
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Term
Glycogen Synthase also is Dephosphorylated by PP1 |
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Definition
•All phosphorylation sites on glycogen synthase can be dephosphorylated by PP1 and/or PP2A
•Dephosphorylation of glycogen synthase is activating
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