Control of Glycogen Metabolism Flashcards
What are the two types of control of the pathways for the synthesis and breakdown of glycogen?
1) Allosteric
2) Hormonal control by covalent modification
Which enzyme in glycogen metabolism is activated allosterically by AMP? Which pathway is it the RDS in?
Glycogen phosphorylase; it is part of the glycogenolysis pathway (breaks down glycogen)
Which enzyme is activated by G6P? Which pathway is it part of?
Glycogen synthase; it is part of the glycogen synthesis pathway.
Which molecules inhibit glycogen phosphorylase and, therefore, the breakdown of glycogen?
ATP and G6P
How does a low concentration of ATP affect glycogen metabolism?
It stimulates glycogen phophorylase and, therefore, glycogen breakdown
How do high concentrations for AMP affect glycogen metabolism?
Activates glycogen phosphorylase and, therefore, the breakdown of glycogen.
How do low concentrations of G6P affect metabolism of glucose?
Inhibits glycogen synthase and, therefore, inhibits glycogen synthesis.
How do high concentrations of G6P and ATP affect glycogen metabolism?
Activates glycogen synthase and inhibits glycogen phosphorylase, thereby stimulating glycogen synthesis.
What molecules move glycogen phosphorylase from the T to the R form?
AMP
What molecules move glycogen phosphorylase from the R to the T form?
ATP and G6P
True or false: glucose moves glycogen phosphorylase from the T to the R form.
False: glucose moves phosphorylase from the R to the T form
True or false: Phosphorylase a is only active when it has been covalently modified?
False; it is active even without covalent modification
True of false: Glycogen synthase is essentially inactive unless it has been dephosphorylated (covalently modified) and G6P is present.
True
What kind of control does the concentration of AMP exert on glycogen phosphorylase?
Allosteric control
What kind of control does phosphorylase kinase and phosphoprotein phosphatase exert on glycogen phosphorylase?
Covalent modification
How does covalent modification affect the control provided by allosteric affectors?
It provides sophisticated control that modulates the enzyme’s responsiveness to allosteric effectors.
How is the interconversion of a and b forms of phosphorylase and synthase accomplished?
By hormone regulated enzyme catalyzed phosphorylation and dephosphorylation.
What is the result of phosphorylation on glycogen phosphorylase?
b form (inactive) goes to a form (active)
What is the result of phosphorylation on glycogen synthase?
a form goes to b form
What is the result of dephosphorylation on glycogen synthase?
b form (inactive) goes to a form (active)
What is the net result of dephosphorylation on glycogen phosphorylase?
a form goes to b form
Which hormones control glycogen metabolism in the liver?
Insulin and glucagon (synthesized in the pancreas)
Which hormones controls glycogen metabolism in muscles and other tissues?
Insulin and epinephrine/norepinephrine
In which direction is the metabolic flux when a large fraction of glycogen enzymes are phosphorylated?
Toward glycogen breakdown (phosphorylase is active and synthase is inactive)
What happens when the concentration of cAMP drops?
phosphorylation rate decreases, synthase is activated, and metabolic flux moves toward glycogen synthesis
What does the binding of glucagon on a liver cell result in?
Generates intracellular cAMP, and results in glucose mobilization from glycogen.
When is glucose release from the pancrease?
When [blood glucose] is less than 5 mM
True or false: Glucagon causes muscle cells to convert glycogen into glucose.
False; muscle cells do not have glucagon receptors and do not, therefore, respond to glucagon.
What is the second messenger of alpha-adrenergic receptors?
Ca2+
What is the second messenger of beta-adrenergic receptors?
cAMP
Which types of cells have both beta- and alpha-adrenergic receptors?
liver
Which types of cells have only beta adrenergic receptors?
muscle
True or false: Muscle cells respond to epinephrine.
True (via beta-adrenergic receptors)
What does epinephrine and norepinephrine cause in muscle cells?
Break down glycogen for glycolysis, thereby generating ATP, and helps muscles cope with stress.
What effect does epinephrine and norepinephrine have on the liver?
Promotes the release of glucagon from the pancreas and, therefore, the breakdown of glycogen to glucose in liver cells.
True or false: epinephrine binds only beta-adrenergic receptors.
False; it binds both beta and alpha adrenergic receptors.
What does the binding of epinephrine by beta-adrenergic receptors cause?
Release of cAMP and glycogen breakdown.
What does the binding of epinephrine by alpha-adrenergic receptors cause?
Stimulates release of Ca2+, reinforcing the cell’s response to cAMP and inactivating glycogen synthase.
True or false: Insulin and epinephrine are antagonists.
True
What triggers the release of insulin?
High blood glucose
Which types of cells have both insulin receptors and insulin-sensitive GLUT 4? Which do not?
Muscle and fat; liver and brain
What happens to cAMP when insulin concentration increases? What affect does this have on glycogen metabolism?
cAMP concentration decreases; causes glycogen metabolism to shift from breakdown to synthesis.
What does insulin promote in muscle?
Glucose storage as glycogen by stimulation of synthesis and inhibition of breakdown.
What does insulin promote in liver?
Glycogen synthesis
True or false: Glucose activates phosphorylase in the liver by binding to the R state.
False; it inhibits phosphorylase by binding to the T state.
Which organs do glycogen storage diseases usually affect?
The liver (cause hepatomegaly and hypoglycemia)
What affect do glycogen storage diseases have on muscle?
Cramps and weakness
