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BC3004: Cell Signalling > Secondary Messengers: cAMP, IP3, DAG > Flashcards

Secondary Messengers: cAMP, IP3, DAG Flashcards

1
Q

Does Adrenaline increase or decrease cAMP?

A

Increase

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2
Q

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

A

Glycogen converted to glucose

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3
Q

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

A

Increases contraction rate

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4
Q

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

A
  • Increases contraction rate
  • Glycogen converted to glucose
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5
Q

Why does TSH increase cAMP in the thyroid?

A

To stimulate thyroxine production

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6
Q

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

A

Decrease

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7
Q

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

A

Increase

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8
Q

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

A

Decrease

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9
Q

How does Adenylyl Cyclase produce cAMP?

A

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

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10
Q

How many isoforms of Adenylyl Cyclase are there?

A

Ten

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11
Q

What is the typical structure of Adenylyl Cyclase?

A
  • Two integral membrane domains each consisting of six hydrophobic α helices
  • Cytosolic catalytic domain and cytosolic C terminal domain between each integral domain
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12
Q

Which secondary messenger activates Protein Kinase A (PKA)?

A

cAMP

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13
Q

Which amino acids does PKA phosphorylate?

A

Serine / Threonine residues on certain proteins

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14
Q

What is the structure of PKA isoforms?

A

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

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15
Q

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

A

Function: Anchors enzyme to membranes
Location: cytoplasm

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16
Q

Where does cAMP bind on PKA?

A

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

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17
Q

How is Glycogen Metabolism regulated by Activation of PKA?

A

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

18
Q

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

A

Decreased

19
Q

What is Glycogen?

A

Polymer of glucose and major stored form of glucose in animals

20
Q

PKA phosphorylates and ACTIVATES / INACTIVATES glycogen synthase

A

Inactivates

21
Q

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

A

Activates

22
Q

p-GPK phosphorylates and ACTIVATES / INACTIVATES glycogen phosphorylase

A

Activates

23
Q

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

A

Activated

24
Q

ACTIVATED / INACTIVATED PKA inhibits glycogen synthesis and stimulates glycogen breakdown

A

Activated

25
Q

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

A
  • 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
26
Q

How is cAMP removed?

A

Removed by cAMP-phosphodiesterases yielding AMP

27
Q

Which ion regulates the activity of some phosphodiesterases?

A

Ca2+

28
Q

How are IP3 and DAG produced?

A

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

29
Q

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

A

PLCβ and PLCγ

30
Q

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

A
  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
31
Q

Where does DAG go after production?

A

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

32
Q

Where does IP3 go after production?

A

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

33
Q

How is Protein Kinase C (PKC) activated?

A

DAG and Ca2+

34
Q

How many isoforms of PKC exist in mammals?

A

At least 6

35
Q

Where is PKC located?

A

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

36
Q

What is the function of PKC in the plasma membrane?

A

Phosphorylates membrane-associated proteins

37
Q

Which organ is PKC enriched in?

A

Brain

38
Q

What cellular processes does PKC play a role in?

A

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

39
Q

What TWO domains does PKC have?

A
  • C-Terminal Catalytic Domain
  • N-Terminal Regulatory Domain
40
Q

Which PKC domain binds DAG and Ca2+?

A

N-Terminal Regulatory Domain

41
Q

What chemical compound can activate PKC?

A

Phorbol Esters

BC3004: Cell Signalling (18 decks)

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