Chapter 13, pages 449-458

G Protein-Coupled Receptors and Second Messengers

You should be able to decode these acronyms: PKA, AC, arr, bARK, cAMP, CaM

• What are the three distinct features of G protein coupled receptors?
• What is an agonist?  What is an antagonist?

b andrenergic receptor system

Be able to describe the parts of b andrenergic receptor system.  Be able to describe the chain of events that occurs after epinephrine binds to this receptor (figure 13-11).  We will discuss it in class.

How is this receptor system turned off?  See figure 13-13.

Be able to draw cyclic AMP.

cAMP activates PKA (cAMP dependent kinase), see figure 13-14 and know this mechanism.   What enzyme does  PKA phosphorylate?  etc, etc...  (Know the cascade of enzyme activation shown in figure 13-15 on page 453.  Note that one molecule of epinephrine produces 10,000 molecules (probably even more) of glucose.  That is signal amplification!  You could sing  a little song (sung to: "the foot bone's connected to the leg bone, the leg bone's connected to the knee bone...") : 

• the epi binds to the receptor,
• the Ga  moves to the  AC
• the AC makes cyclic AMP
• the cAMP binds to the PKA
• the PKA phosphorylates the phosphorylase b  kinase (ok the rythym is rough here)
• the pb kinase phosphorylates phosphorylase b
• phosphorylase b cleaves the glycogen

Note:  only the liver has the enzyme to remove the phosphate from glucose-1-P--the final product of this cascade.  (What is the liver's job description?)

There are many other enzymes that are target of PKA, they are listed in table 13-3.   Just be aware of this information.

You should be able to describe how the Gs protein activates AC and how the system is desensitized.

• What happens to the a subunit?
• What controls the intracellular levels of cAMP?  (Coffee and tea contain molecules that inhibit this control mechanism.)
• What does the gb subunit do?
• What does bARK do?  What binds after that?
• Where does the receptor complex go?
• We are trying to determine what happens to the epinephrine--maybe the internet knows.

Practice writing a paragraph (or two)  that describes this receptor.

Examples of G_i coupled receptors

Somatostatin binds to a receptor that is coupled to a Gi protein. 

• How is Gi the same as Gs?  How do they differ?
• What is the effect of PGE₁ binding to its receptor on an adipocyte? 
• How can epinephrine cause a decrease in cAMP in cells that have a2 andrenergic receptors?

More Serpentine receptors

Phospholipase C is activated by a Gq protein that is coupled to a serpentine receptor.   Gq is similar to the Gsa subunit. You should be able to describe this activation cascade.

How do the phorbol ester tumor promoters exert their effects?  Why are they more potent activators?  What do they affect?

Once phospholipase C has increased intracellular Ca⁺² levels, then Ca⁺² binds to Calmodulin (CaM).  CaM associates with a number of different proteins, one of which is Ca⁺²/calmodulin dependent kinase (CaM-kinase).  This enzyme phosphorylates a number of other target enzymes.  CaM is also associated with phosphorylase b kinase (pb kinase) in the muscle, when Ca⁺² binds to CaM, the pb kinase is activated and the net result is that glycogen is broken down.