Anonymous
06-05-2004, 07:07 PM
Question 7: A secondary action of epinephrine in liver
To which additional adrenergic receptor subtype does epinephrine bind in order to further activate glycogen phosphorylase in liver?
A. alpha-1
B. alpha-2
C. beta-1
D. a novel beta-3 subtype
Think of this as an auxiliary action of epinephrine to boost the action of glycogen phosphorylase in a true emergency. Recall that phosphorylase kinase is the enzyme that phosphorylates and activates glycogen phosphorylase, and that phosphorylase kinase b, the inactive form, can be phosphorylated to phosphorylase kinase "a" (active) as part of a phosphorylation cascade initiated by cAMP and protein kinase A.
A part of the regulation you may have forgotten is that intracellular calcium can activate phosphorylase kinase b even in the absence of the phosphorylation signal. This effect would then activate even those molecules of phosphorylase kinase that did not become phosphorylated in the cascade, creating an additive effect to boost glycogen hydrolysis.
Intracellular calcium would be naturally released in muscle with "fight or flight" contractions to accomplish this additive activation, but how can this happen in liver? The answer is a second type of adrenergic receptor to which epinephrine can bind to boost intracellular calcium. This occurs via the Gp/phospholipase C/IP3 pathway. The only remaining issue: which adrenergic receptor type is linked to Gp?
http://www.biology.arizona.edu/biochemistry/problem_sets/carbomet/graphics/07t.gif
Secondary action of epinephrine in liver
ans:
A. alpha-1
This seems like a picky question, but recall that the liver is one of the main sources of quick fuel in the "fight or flight" response, and so it needs a second pathway for maximum responsiveness. Having already dispensed with the beta adrenergic receptors in the previous question, we can also eliminate the alpha-2 receptor, which would actually work against glycogenolysis by lowering cAMP and thus shutting down the protein kinase A-initiated cascade.
The only receptor left is alpha-1, the correct answer. Alpha-1 receptors act by generating DAG/IP3 signals and mobilizing intracellular Ca++. Elevated intracellular Ca++ then allosterically activates phosphorylase kinase in the absence of phosphorylation, which then can activate glycogen phosphorylase via an abbreviated phosphorylation pathway. (There is one other allosteric activator besides Ca++ that can activate glycogen phosphorylase by bypassing the normal PKA step - the (non-cyclic!) AMP "cellular distress signal", which acts to directly activate glycogen phosphorylase b in the absence of a phosphorylation signal.)
To which additional adrenergic receptor subtype does epinephrine bind in order to further activate glycogen phosphorylase in liver?
A. alpha-1
B. alpha-2
C. beta-1
D. a novel beta-3 subtype
Think of this as an auxiliary action of epinephrine to boost the action of glycogen phosphorylase in a true emergency. Recall that phosphorylase kinase is the enzyme that phosphorylates and activates glycogen phosphorylase, and that phosphorylase kinase b, the inactive form, can be phosphorylated to phosphorylase kinase "a" (active) as part of a phosphorylation cascade initiated by cAMP and protein kinase A.
A part of the regulation you may have forgotten is that intracellular calcium can activate phosphorylase kinase b even in the absence of the phosphorylation signal. This effect would then activate even those molecules of phosphorylase kinase that did not become phosphorylated in the cascade, creating an additive effect to boost glycogen hydrolysis.
Intracellular calcium would be naturally released in muscle with "fight or flight" contractions to accomplish this additive activation, but how can this happen in liver? The answer is a second type of adrenergic receptor to which epinephrine can bind to boost intracellular calcium. This occurs via the Gp/phospholipase C/IP3 pathway. The only remaining issue: which adrenergic receptor type is linked to Gp?
http://www.biology.arizona.edu/biochemistry/problem_sets/carbomet/graphics/07t.gif
Secondary action of epinephrine in liver
ans:
A. alpha-1
This seems like a picky question, but recall that the liver is one of the main sources of quick fuel in the "fight or flight" response, and so it needs a second pathway for maximum responsiveness. Having already dispensed with the beta adrenergic receptors in the previous question, we can also eliminate the alpha-2 receptor, which would actually work against glycogenolysis by lowering cAMP and thus shutting down the protein kinase A-initiated cascade.
The only receptor left is alpha-1, the correct answer. Alpha-1 receptors act by generating DAG/IP3 signals and mobilizing intracellular Ca++. Elevated intracellular Ca++ then allosterically activates phosphorylase kinase in the absence of phosphorylation, which then can activate glycogen phosphorylase via an abbreviated phosphorylation pathway. (There is one other allosteric activator besides Ca++ that can activate glycogen phosphorylase by bypassing the normal PKA step - the (non-cyclic!) AMP "cellular distress signal", which acts to directly activate glycogen phosphorylase b in the absence of a phosphorylation signal.)