Flashcards in Biological Signalling: GPCR Deck (30)
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1
What does GPCR stand for?
G protein coupled receptor
2
Epinephrine is a derivative of _____
tyrosine
3
What are 3 components of heterotrimeric GPCR Signalling?
1. plasma membrane receptor with 7 TM
2. heterotrimeric guanosine nucleotide binding protein (G-protein)
3. intracellular enzyme that generates a 2nd messenger
4
What does the binding of the ligand to the beta adrenergic receptor cause?
- structural change on cytoplasmic side
- G alpha,beta,gamma bind the B receptor
- Gprotein is GDP bound inactive
5
Gprotein bound to activated receptor causes:
- GDP/GTP exchange and binding affinity
- activated G protein = change shape = kick out the Ga-GTP
6
Gas - GTP associates with
Adenylyl cyclase
7
AC catalyzes the formation of
- ATP to form cAMP
8
cAMP activates
PKA
protein kinase a
which phosphorylates cellular proteins that cause a cellular response to epinephrine
9
Where can this beta adrenergic pathway be stopped?
- Gai (inactivate/inhibitory) binds and deactivates adenylyl cyclase (cant form cAMP)
- phosphodiesterase PDE breaks down cAMP to 5'AMP
10
What does caffeine do to this pathway?
- inhibits PDE
- prevents breakdown of cAMP
11
Gs bound GDP is ____
inactive
cannot activate AC
12
Gs contact with hormone receptor (beta adrenergic receptor) causes
GTP displaces GDP bound to Gs
13
Gs bound GTP _____
- dissociates into Gsa and Gsby subunits
14
Active complex of Gs protein is ___
Gsa - GTP
- activates adenylyl cyclase
15
What do Gai proteins do?
- inhibit the formation of second messenger
- via cytoplasmic facing enzyme AC
16
What are 4 turn off mechanisms?
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
What is the first step of internalizing the epinephrine receptor to turn off epinephrine mechanism?
- phosphorylation of the b adrenergic receptor
- on serine residue of C terminus
18
What phosphorylates the beta adrenergic receptor?
bARK
- beta adrenergic receptor kinase
19
bAR forms a complex with _____
beta arrestin bARR
20
Receptor arrestin complex does what?
- enters the cell by endocytosis
- arrestin dissociates and receptor is dephosphorylated and then returns back to cell surface
21
What other G proteins are there?
Gaq
22
What does Gaq stimulate?
- PL-C enzyme (instead of AC)
- increase DAG and IP3
23
What does DAG activate?
PKC (cell growth responses)
24
What does IP3 activate?
Ca2+ released inside the cell for smooth muscle response and Ca2+dependent signalling
25
What are two types of neurotransmitters for metabotropic receptors? (GPCR)
- biogenic amines
- neuropeptides
26
List some biogenic amines:
- acetylcholine
- nicotinic receptors
- muscarinic receptors : Gai and Gaq
- Epinephrine and norepinephrine
- dopamine
- serotonin
27
What does M1-5 do?
muscarinic receptor:
- stimulates Gai and Gaq
- decreased HR and contraction
- increased smooth muscle contraction of gut (rest and digest)
28
What does epinephrine and norepinephrine do?
- 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
Dopamine?
Dopamine 1 receptors activate Gas = euphoria
Dopamine 2 receptors activate Gai = motor coordination
30
