cAMP, IP3, and NO pathways

Question 1

What is the difference between a short term pathway and a long term pathway?

Answer 1

Short term pathways are things cells do every day. Long term pathways usually affect gene expression, so they take longer to activate and don’t get turned on as often

Question 2

What kind of receptor is used in short term pathways?

Answer 2

G-protein coupled receptor - GPCR

Question 3

What is the structure of a GPCR?

Answer 3

7 transmembrane domains with the N-terminus in the extracellular side and the C-terminus in the intracellular side. They are receptors attached to a G-protein

Question 4

What kind of G-protein is attached to a GPCR? What are its characteristics?

Answer 4

Large, heterotrimeric. Has an alpha, beta, and gamma subunit. The alpha subunit is where GTP or GDP is bound

Question 5

What happens to the G-protein when it gets activated?

Answer 5

The subunits separate. The alpha subunit goes off with the GTP and does something, while the beta and gamma subunits stay together and go off and do another thing

Question 6

Why have the beta and gamma subunits of the G-protein in the first place?

Answer 6

They are an off switch for the G-protein. The alpha subunit gets deactivated when bound to the beta and gamma subunits

Question 7

What are the steps in the cAMP pathway? (liver cells)

Answer 7

1. Epinephrine binds to the epinephrine receptor
2. Activates the G-protein: Gs
3. The Gsα-GTP subunit binds to adenylyl cyclase
4. Adenylyl cyclase produces cAMP
5. The cAMP activates PKA
6. PKA will phosphorylate phosphorylase kinase
7. Phosphorylase kinase phosphorylates glycogen phosphorylase, which then breaks down glycogen

Question 8

What is adenylyl cyclase? What is its structure and function?

Answer 8

An enzyme that converts ATP to cAMP. It has 12 transmembrane domains

Question 9

What is cAMP?

Answer 9

Cyclic adenosine monophosphate. It is a secondary messenger molecule created in very large quantities by adenlylyl cyclase

Question 10

How does cAMP activate PKA?

Answer 10

PKA has two subunits, regulatory and catalytic. cAMP binds to the regulatory subunits, which cause them to release the catalytic subunits that are now active

Question 11

What are 4 ways to turn off the cAMP pathway?

Answer 11

1. Shut off the G-protein
2. Epinephrine dissociates from the receptor
3. Break down the cAMP floating around
4. Removing the phosphates off things that were phosphorylated by PKA

Question 12

What are the steps in the IP3 pathway? (blood platelets)

Answer 12

1. Thrombin binds to the receptor
2. G protein is activated, which activates phospholipase C
3. PIP2 is cleaved into DAG and IP3
4. IP3 binds to the calcium ion channel in the smooth ER and opens it
5. Calcium diffuses out
6. Calcium binds to calmodulin
7. The calmodulin complex binds to PKC and translocates it to the membrane
8. PKC will phosphorylate targets at the membrane

Question 13

What is the purpose of the IP3 pathway?

Answer 13

Release calcium stored in the smooth ER

Question 14

Why is calcium stored in the smooth ER?

Answer 14

It activates a lot of enzymes, so it gets stored until it is needed

Question 15

What is the function of phospholipases? What does phospholipase C break down?

Answer 15

They break down phosphorylated lipids. PLC breaks down PIP2

Question 16

What is the purpose of DAG being created?

Answer 16

It helps with activating PKC, but some cell types don’t use this part of the pathway

Question 17

What are the steps in the NO pathway?

Answer 17

1. Acetylcholine binds to the GPCR in endothelial cells of blood vessels
2. The IP3 pathway is activated
3. NO synthase is activated
4. NO synthase converts arginine and oxygen to citruline and NO
5. NO diffuses across membranes and tissues into the smooth muscle cells where it binds to the NO receptor in the cytoplasm
6. Guanylyl cyclase is activated and produces cGMP
7. cGMP binds to and activates PKG, which will phosphorylate targets and lead to muscle relaxation