Signaling 1

Question 1

What is the role of glucagon in the liver?

Answer 1

• Breakdown glycogen
• Stimulate gluconeogenesis
• Form and release ketone bodies from FA breakdown

Question 2

What is the role of glucagon in the adipose tissue?

Answer 2

• Mobilize fatty acids from adipose tissue to the liver where they will be metabolized for energy (ATP production) and ketone body formation

Question 3

Glucagon is an example of what kind of receptor?

Answer 3

GPCR - specifically the stimulatory G protein (G_as)

Question 4

What is the general mechanism for GPCR proteins?

Answer 4

Question 5

In GPCR, what controls protein structure?

Answer 5

GTP binding and GTPase activity of G protein

Question 6

How does G_as exchange GDP for GTP?

Answer 6

With the help of GTP - GDP Exchange Factors (GEFs). The reason these are needed is because G_as has similar affinity for both GDP and GTP so help is needed to make the exchange. In a cell that is well supplied with nutrients, the [GTP] >>> [GDP] so once GDP is removed it will easily be replaced by GTP due to its abundance.

Question 7

Once G_as stimulates Adenylyl Cyclase, the GTP bound to G_as is hydrolyzed. Why does G_as require GAP (GTPase activating protein) to do this?

Answer 7

G_as is a poor GTPase so it needs help of GAP to carry out function

Question 8

cAMP is made when Adenylyl Cyclase is stimulated by GPCRs. What regulatory mechanism in the cell must be overcome for this signal to be transduced further?

Answer 8

Phoshphodiesterases in the cell act to convert cAMP to AMP, thus damping down the effects of the signaling cascade. GPCRs overcome this by acting to amplify the signal such that the phosphodiesterases become saturated and cAMP signal can be transduced

Question 9

How can PKA exert its effects immediately? More long term?

Answer 9

Immediately - phosphorylate enzymes to regulate activity

Long term - phosphorylate transcription factors to regulate activity

Question 10

Two examples of GPCRs are Beta-adrenergic receptors and alpha 1 receptors. Compare and constrast these.

Answer 10

• Both GPCRs
• Beta adrenergic signals via G_as … alpha 1 signals through G_aq
• Beta adrenergic activates adenylyl cyclase which then activates PKA via cAMP … alpha 1 activates Phospholipase C directly which then uses PIP as a second messenger

Question 11

What are the ligands for adrenergic GPCRs (both beta and alpha 1)?

Answer 11

Epinephrine

Norepinephrine

Question 12

What G protein is acting in alpha 1 adrenergic receptors?

Answer 12

G_aq

Question 13

Describe the process of GPCR desensitization and downregulation.

Answer 13

Desensitization - phosphorylation of receptor blocks further activation of receptor, receptors becomes desensitized to signal. GPCR still present on cell surface but it is inactive.

Downregulation - decreasing the amount of receptor at cell surface, requires internalization and/or degradation

Question 14

What is the difference between homologous desensitization and heterologous desensitization?

Answer 14

Homologous - activated receptor is desensitized

Heterologous - activation of one receptor alters activity of a different receptor that is not activated