G Coupled Protein Receptors

Question 1

Tell us five things you know about GCPRs

Answer 1

*transmembrane proteins

*single polypeptide chain

*Wound around the membrane 7 times

*Have 2 domains:
-N terminal extracellular domain - interacts with agonist
-C terminal intracellular domain -interacts with G protein

Question 2

What reactions are triggers when ligands bind to the N terminal extracellular domain

Answer 2

Intracellular cascade of reactions

Question 3

Tell us 3 features of G proteins

Answer 3

• Membrane resident proteins
• Have 3 subunits: alpha, beta, gamma
• In the resting state, they are called alpha-beta gamma dimer

Question 4

What is joined to the alpha subunit in the resting state?

Answer 4

GDP

Question 5

What happens when an agonist binds to the N terminal extracellular domain?

Keywords/hints:
GDP, intracellular domain, enzymes, GTP, alpha, beta, gamma subunits, activation, conformational change, ion gated channels, kinase, dimer

Answer 5

• A conformational change occurs
• The c terminal intracellular domain interacts with a G protein
• GDP will dissociate from the alpha subunit, GTP will bind = activation of the protein
• The a subunit will seperate from the beta-gamma dimer.
• The a subunit will interact with either phospholipase C or adenylate cyclase
• The beta-gamma dimer will bind to ion gated channels and kinases to activate them

Question 6

What two enzymes does the alpha subunit with GTP bound to it activate?

Answer 6

Phospholipase C and Adenylate Cyclase

Question 7

3 features of adenylate cylase

Answer 7

• Membrane-bound enzyme
• Stimulated by Gs protein
• Inhibited by Gi protein

Question 8

What happens when adenylate cyclase is activated?

Answer 8

•ATP is converted into cAMP
•cAMP activates dependent protein kinases, which phosphorylate enzymes

Question 9

1 feature of Phospholipase C

Answer 9

It is activated by the Gq protein

Question 10

What does Phospholipase C do?

Answer 10

Catalyses the cleavage of phosphatidylinositol bisphosphate into DAG and IP3

Question 11

2 features of the IP3 receptor

Answer 11

• Ligand-gated
  calcium channel
• Found in the membrane of the endoplasmic reticulum

Question 12

What happens when IP3 binds to the IP3 receptor?

Answer 12

There is a release of calcium ions into the cytoplasm

Question 13

Main goal of the IP3 receptors?

Answer 13

Increase the cytosolic calcium concentration

Question 14

Why are calcium ions important?

Answer 14

They aid with:
-muscle contraction
-enzyme activation

Question 15

What does the release of DAG do?

Answer 15

Increases the levels of protein kinase C within the cell. This leads to the phosphorylation of enzymes and proteins.

Question 16

What does phosphodiesterase do?

Answer 16

Breaks down cAMP

Question 17

How is protein kinase A activated?

Answer 17

When cAMP binds to it

Question 18

What enzyme breaks down acetylcholine?

Answer 18

acetylcholinesterase

Question 19

What enzyme catalyses the formation of acetylcholine?

Answer 19

choline acetyltransferase

Question 20

What effect does the influx of calcium ions in the presynaptic neurone have on the vesicles?

Answer 20

It causes vesicles containing acetylcholine to fuse with membrane

Question 21

How is choline transported into the neurone?

Answer 21

By energy and sodium-dependent transporters

Question 22

What does an influx of sodium ions into the neurone do?

Answer 22

Depolarises it (activates)

Question 23

Describe what happens when choline and sodium ions are transported in to the neurone? (very detailed)

Answer 23

• Choline binds with acetyl Coenzyme A to form acetylcholine; this is catalysed by cholineltransferase
• Acetylcholine is transported into a presynaptic vesicle
• Movement of sodium ions causes the action potential of the neurone to change, which then stimulates the opening of voltage-sensitive calcium channels to open

-The influx of calcium ions into the neurone causes the fusion of the presynaptic vesicles with the membrane, releasing acetylcholine

• Acetylcholine then binds to the postsynaptic receptor, which leads to a cholinergic response. It also binds to the presynaptic neurone receptorinhibiting the release of more acetylcholine into the synaptic cleft

-Acetylcholinesterase inhibits acetylcholine function by breaking it down into choline (taken back into the neurone) and acetate.

Question 24

What do the presynaptic vesicles prevent from happening to acetylcholine?

Answer 24

Degradation

Question 25

What are the two types of cholinergic receptors?

Answer 25

nicotinic and muscarinic

Question 26

What does double inhibition lead to?

Answer 26

excitation

Question 27

What is GABA?

Answer 27

inhibitory neurotransmitter