Secondary Messengers: cAMP, IP3, DAG

Question 1

Does Adrenaline increase or decrease cAMP?

Answer 1

Increase

Question 2

What is the cellular response to increased cAMP in the liver?

Answer 2

Glycogen converted to glucose

Question 3

What is the cellular response to increased cAMP in the heart?

Answer 3

Increases contraction rate

Question 4

What is the cellular response to increased cAMP in the skeletal muscle?

Answer 4

• Increases contraction rate
• Glycogen converted to glucose

Question 5

Why does TSH increase cAMP in the thyroid?

Answer 5

To stimulate thyroxine production

Question 6

Do Adenosine and Prostaglandin E1 increase or decrease the production of cAMP?

Answer 6

Decrease

Question 7

Does activation of Gαs increase or decrease the production of cAMP?

Answer 7

Increase

Question 8

Does activation of Gαi increase or decrease the production of cAMP?

Answer 8

Decrease

Question 9

How does Adenylyl Cyclase produce cAMP?

Answer 9

Isoenzymes catalyse the removal of the two terminal phosphate groups from ATP and cyclisation of AMP

Question 10

How many isoforms of Adenylyl Cyclase are there?

Answer 10

Ten

Question 11

What is the typical structure of Adenylyl Cyclase?

Answer 11

• Two integral membrane domains each consisting of six hydrophobic α helices
• Cytosolic catalytic domain and cytosolic C terminal domain between each integral domain

Question 12

Which secondary messenger activates Protein Kinase A (PKA)?

Answer 12

cAMP

Question 13

Which amino acids does PKA phosphorylate?

Answer 13

Serine / Threonine residues on certain proteins

Question 14

What is the structure of PKA isoforms?

Answer 14

Cytosolic heterotetramers consisting of two regulatory subunits (R) and two catalytic subunits (C)

Question 15

What is the function and location of the two Regulatory subunits isoforms of PKA?

Answer 15

Function: Anchors enzyme to membranes
Location: cytoplasm

Question 16

Where does cAMP bind on PKA?

Answer 16

Binds to the regulatory subunits of PKA to ‘release’ the catalytic subunits

Question 17

How is Glycogen Metabolism regulated by Activation of PKA?

Answer 17

Catalytic subunits once dissociated can phosphorylate cellular proteins leading to glycogen breakdown

Question 18

Does increased or decreased cAMP stimulate glycogen synthesis and inhibits glycogen breakdown

Answer 18

Decreased

Question 19

What is Glycogen?

Answer 19

Polymer of glucose and major stored form of glucose in animals

Question 20

PKA phosphorylates and ACTIVATES / INACTIVATES glycogen synthase

Answer 20

Inactivates

Question 21

PKA phosphorylates and ACTIVATES / INACTIVATES glycogen phosphorylase kinase (GPK)

Answer 21

Activates

Question 22

p-GPK phosphorylates and ACTIVATES / INACTIVATES glycogen phosphorylase

Answer 22

Activates

Question 23

p-Glycogen Phosphorylase is ACTIVATED / INACTIVATED and cleaves glycogen sequentially of glucose residues

Answer 23

Activated

Question 24

ACTIVATED / INACTIVATED PKA inhibits glycogen synthesis and stimulates glycogen breakdown

Answer 24

Activated

Question 25

How does cAMP regulate the transcription of target genes involved in glucose metabolism?

Answer 25

* cAMP activates PKA * PKA interacts with p-CRE binding protein (CREB) in nucleus * p-CREB binds to CRE (cAMP response element) of DNA and activates target genes

Question 26

How is cAMP removed?

Answer 26

Removed by **cAMP-phosphodiesterases** yielding AMP

Question 27

Which ion regulates the activity of some phosphodiesterases?

Answer 27

Ca2+

Question 28

How are IP3 and DAG produced?

Answer 28

By the action of **phospholipase C (PLC)** isoenzymes on the lipid **phosphotidylinositol 4,5-bisphosphate (PIP2)**

Question 29

What are the TWO isoforms of Phospholipase C (PLC)?

Answer 29

PLCβ and PLCγ

Question 30

What is the mechanism of action in the production of IP3 and DAG?

Answer 30

1. **PLCβ activated** through G-proteins **following hormone binding** 2. **PLCγ** located in the cytosol are **recruited to autophosphorylated RTKs through SH2 domain** 3. **PLCγ** brought into the vicinity of **PIP2** substrate 4. **Phospholipase C cleavage of PIP2** produces IP3 and DAG

Question 31

Where does DAG go after production?

Answer 31

**Stays at plasma membrane** and **co-activates protein kinase C (PKC)** * also important in lipid synthesis

Question 32

Where does IP3 go after production?

Answer 32

Goes to **ER intracellular Ca2+ storage sites** and **opens a Ca2+ sensitive channel to release Ca2+**

Question 33

How is Protein Kinase C (PKC) activated?

Answer 33

DAG and Ca2+

Question 34

How many isoforms of PKC exist in mammals?

Answer 34

At least 6

Question 35

Where is PKC located?

Answer 35

Cytosolic but can translocate to plasma membrane in the presence of DAG

Question 36

What is the function of PKC in the plasma membrane?

Answer 36

Phosphorylates membrane-associated proteins

Question 37

Which organ is PKC enriched in?

Answer 37

Brain

Question 38

What cellular processes does PKC play a role in?

Answer 38

Functions as monomer in cell **proliferation**, **differentiation**, **angiogenesis** and **apoptosis**

Question 39

What TWO domains does PKC have?

Answer 39

* C-Terminal Catalytic Domain * N-Terminal Regulatory Domain

Question 40

Which PKC domain binds DAG and Ca2+?

Answer 40

N-Terminal Regulatory Domain

Question 41

What chemical compound can activate PKC?

Answer 41

Phorbol Esters