Biological Signalling: GPCR Flashcards

1
Q

What does GPCR stand for?

A

G protein coupled receptor

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2
Q

Epinephrine is a derivative of _____

A

tyrosine

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3
Q

What are 3 components of heterotrimeric GPCR Signalling?

A
  1. plasma membrane receptor with 7 TM
  2. heterotrimeric guanosine nucleotide binding protein (G-protein)
  3. intracellular enzyme that generates a 2nd messenger
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4
Q

What does the binding of the ligand to the beta adrenergic receptor cause?

A
  • structural change on cytoplasmic side
  • G alpha,beta,gamma bind the B receptor
  • Gprotein is GDP bound inactive
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5
Q

Gprotein bound to activated receptor causes:

A
  • GDP/GTP exchange and binding affinity

- activated G protein = change shape = kick out the Ga-GTP

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6
Q

Gas - GTP associates with

A

Adenylyl cyclase

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7
Q

AC catalyzes the formation of

A
  • ATP to form cAMP
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8
Q

cAMP activates

A

PKA
protein kinase a
which phosphorylates cellular proteins that cause a cellular response to epinephrine

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9
Q

Where can this beta adrenergic pathway be stopped?

A
  • Gai (inactivate/inhibitory) binds and deactivates adenylyl cyclase (cant form cAMP)
  • phosphodiesterase PDE breaks down cAMP to 5’AMP
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10
Q

What does caffeine do to this pathway?

A
  • inhibits PDE

- prevents breakdown of cAMP

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11
Q

Gs bound GDP is ____

A

inactive

cannot activate AC

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12
Q

Gs contact with hormone receptor (beta adrenergic receptor) causes

A

GTP displaces GDP bound to Gs

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13
Q

Gs bound GTP _____

A
  • dissociates into Gsa and Gsby subunits
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14
Q

Active complex of Gs protein is ___

A

Gsa - GTP

- activates adenylyl cyclase

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15
Q

What do Gai proteins do?

A
  • inhibit the formation of second messenger

- via cytoplasmic facing enzyme AC

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16
Q

What are 4 turn off mechanisms?

A
  1. epinephrine dissociates
  2. GTPase: timer that G-a subunit hydrolyses GTP (goes back to GDP)
  3. PDE: cAMP broken down to 5’AMP
  4. Internaliation of receptors beta adrenergic receptor is phosphorylated and internalized (endocytosis)
17
Q

What is the first step of internalizing the epinephrine receptor to turn off epinephrine mechanism?

A
  • phosphorylation of the b adrenergic receptor

- on serine residue of C terminus

18
Q

What phosphorylates the beta adrenergic receptor?

A

bARK

- beta adrenergic receptor kinase

19
Q

bAR forms a complex with _____

A

beta arrestin bARR

20
Q

Receptor arrestin complex does what?

A
  • enters the cell by endocytosis

- arrestin dissociates and receptor is dephosphorylated and then returns back to cell surface

21
Q

What other G proteins are there?

A

Gaq

22
Q

What does Gaq stimulate?

A
  • PL-C enzyme (instead of AC)

- increase DAG and IP3

23
Q

What does DAG activate?

A

PKC (cell growth responses)

24
Q

What does IP3 activate?

A

Ca2+ released inside the cell for smooth muscle response and Ca2+dependent signalling

25
Q

What are two types of neurotransmitters for metabotropic receptors? (GPCR)

A
  • biogenic amines

- neuropeptides

26
Q

List some biogenic amines:

A
  • acetylcholine
  • nicotinic receptors
  • muscarinic receptors : Gai and Gaq
  • Epinephrine and norepinephrine
  • dopamine
  • serotonin
27
Q

What does M1-5 do?

A

muscarinic receptor:

  • stimulates Gai and Gaq
  • decreased HR and contraction
  • increased smooth muscle contraction of gut (rest and digest)
28
Q

What does epinephrine and norepinephrine do?

A
  • opposite to M15
  • a1 receptor activates Gaq and a2 receptor activates Gai
  • relax smooth muscle of gut
  • vasoconstriction of gut blood vessel, glucagon release
  • increase blood FFA and glucose
  • beta 1, 2, 3, (bAR) activates Gas:
  • increased HR and contraction
  • vasodilation of skeletal muscle blood vessels
29
Q

Dopamine?

A

Dopamine 1 receptors activate Gas = euphoria

Dopamine 2 receptors activate Gai = motor coordination

30
Q

How are steroid hormone receptors transported and how does it target DNA?

A
  • carrier serum proteins
  • diffuse across PM
  • bind Rec (receptor protein)
  • conformational change of receptor protein
  • Rec binds HRE in DNA
  • regulates transcription of mRNA