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Regulation of Carbohydrate Metabolism Problem Set

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
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.)

B. alpha-2
C. beta-1
D. a novel beta-3 subtype

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March 16, 2001
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