REGULATION OF GLYCOGEN METABOLISM

Mobilization and synthesis of glycogen under hormonal control.
Three hormones involved:
1) insulin
51 a.a. protein made by cells of pancreas.
Secreted when [glucose] high --> increases rate of glucose transport into muscle and fat via
GLUT4 glucose transporters.
Stimulates glycogen synthesis in liver.
2) glucagon
29 a.a. protein secreted by cells of pancreas.
Operational under low [glucose].
Restores blood sugar levels by stimulating glycogen degradation.
3) epinephrine
Stimulates glycogen mobilization to glucose 1-phosphate --> glucose 6-phosphate.
Increases rate of glycolysis in muscle and the amount of glucose in bloodstream.
3
Occurs in response to fight-or-flight response.
Binds to -adrenergic receptors in liver and muscle and 1 receptors in liver cells.
Binding of epinephrine or glucagon to receptors activates adenylate cyclase, which is a
membrane-traversing enzyme that converts ATP --> cAMP --> activates protein kinase A.
Binding of epinephrine to 1 receptors activates IP3 pathway --> protein kinase C -->
phosphorylation of insulin receptors -> insulin cannot bind.
Regulation of glycogen phosphorylase and glycogen synthase
Reciprocal regulation.
_ Glycogen synthase -P --> inactive form (b).
_ Glycogen phosphorylase-P ---> active (a).
When blood glucose is low, protein kinase A activated through hormonal action
of glucagon --> glycogen synthase inactivated and phosphorylase kinase
activated --> activates glycogen phosphorylase --> glycogen degradation
occurs.
Phosphorylase kinase also activated by increased [Ca2+] during muscle
contraction.
To reverse the same pathway involves protein phosphatases, which remove
phosphate groups from proteins --> dephosphorylates phosphorylase
kinase and glycogen phosphorylase (both inactivated), but
dephosphorylation of glycogen synthase activates this enzyme.
Protein phosphatase-1 activated by insulin --> dephosphorylates glycogen
synthase --> glycogen synthesis occurs.
In liver, glycogen phosphorylase a inhibits phosphatase-1 --> no glycogen
synthesis can occur.
Glucose binding to protein phosphatase-1 activated protein phosphatase-1 -->
it dephosphorylates glycogen phosphorylase --> inactivated --> no
glycogen degradation.
Protein phosphatase-1 can also dephosphorylate glycogen synthase --> active.