G Protein Receptor Effector Mechanisms

Question 1

What is the clincial significance of G protein coupled receptors?

Answer 1

40 of all presecitption drugs affect GPCRs indirectly or directly, and there a huge number of applications for drugs using GPCRS

Question 2

What are some of the stiumuli that G protein coupled receptors respond too?

Answer 2

Neurotransmitters, large glycoproteins, peptide and non peptide hormones, ions.

Question 3

What are some of the structural features of a g protein coupled receptor?

Answer 3

They are a single polypeptide chain comprising of 300-1200 amino acids, they have 7 transmembrane domain spanning regions, they have a extracellular n terminal, and there are 800 found in the human genome

Question 4

What are the two possible regions of ligand binding on a g protein coupled receptor?

Answer 4

Can be formed by 2-3 of the transmembrane domains, the n terminal region or other eaxtracelluar domains are forming the transmembrane site

Question 5

Give examples of loss of function mutations on g protein coupled receptors.

Answer 5

Neuorgenic diabeted inspipidus, V2 vasocon recpetor, retinus plimetosa, loss of function of rhosposin

Question 6

How does a GOCR generate a change in the cellular activity?

Answer 6

The activated GPCR interacts with the G protein and causes GDP to exchange for GTP on the a subuni, the a and B-y complexes dissocate, into a-GTP and B-Y and each interact with effector proteins to cause a cellular response

Question 7

What are the structural features of the G protein?

Answer 7

Heterotrimeric, with a alpha, beta and gamma subunit.

Question 8

How is the G protein activity stopped?

Answer 8

GTPase activity hydrolyses GTP-GDP, and than the a-GDP and the By reform an inactive heterotrimeric complex

Question 9

How does the chlorea toxin affect the function of G proteins?

Answer 9

They ADP ribosylate specific proteins, which interferes with the GTPase activity of Gsa and therefore Gsa becomes irreversibly activated

Question 10

How does the whooping cough (pertissus) twoxin affect G proteins?

Answer 10

Ita ADpp-ribosyltes specific proteins, and this interferes the GTP/GDP exhcnage on the Gia causing it to become irreversibly inactivated

Question 11

How mny of the different subunits are encoded for in the human genome?

Answer 11

20 Ga, 5Gb, 12 Gy

Question 12

What are the three superfamilies of cell surface receptors?

Answer 12

G protein coupled (7TM), receptors with intrinsic enzymatic activity and ligand gated ion channels

Question 13

Name some of the different effector enzymes for g proteins

Answer 13

Adenylyl cyclase, phospholipase c, cGMP phosphodiesterase, phosphodimer 3 kinase

Question 14

What are the two different receptor effector mechanisms?

Answer 14

Effectors can be enzymes, or ion channels

Question 15

How does andylnly cyclase invoke a cellular response?

Answer 15

CAMP, which activates a cyclic AMP dependant kinase, attaching to one of the regulroty subunits on this enzyme and freeing the catalytic subunit.

Question 16

How does Phospholipase C invoke a cellular response?

Answer 16

Hydrolysis of a membrane phospholipid PIP2 to achieve 2 second messengers, InsP3 and DAG, InsP3 interacts with specific intracellular receptors on the ER and allows Ca2+ to be leave the ER,activation of a2+ dependant kinase, or DAG which interacts with. Family of protein kinases.

Question 17

What is the definning factor of cGMP phosphrylase activity?

Answer 17

Degrade instead of activating the second messengers, activated in the light, closes the channels and therefore causes hyper polarisation of the membrane, sending a signal to the CNS.

Question 18

What are the three mechanisms of signal amplification for G proteins.

Answer 18

Activated receptor can cause sequential GTP/GDP activation, and activated G-aGtP/gBy can activate a number of effector molecules, and effector molecules act catalytically so can activate a number of molecules.

Question 19

What are some of the mechanisms for deactivation of the signalling pathways?

Answer 19

Once a receptor has productively interacted with a protein binding or agnosit moelcule, it is weakened and causes receptor dissicoaitijon to occur, there are cellular factors that stimulate the instrisicn ATPase activity of the Ga subunit, and the enzymatic cascades can also cause activation of the kinase

Question 20

How do g proteins regulate chonotrophy of the heart?

Answer 20

M2 receptors re activated, which increases the open probability of the K+ channel which slows the the activation of an action potential and therefore has a activation of a negative chronotrophic affect.

Question 21

How is iontropy regulated in the heart?

Answer 21

Activation of B-adrenoreceptros, increases cAMP formation and open probability of volatge gated Ca2+ channels, as cAMP dependant kinase is acitivated which phosphylates to open the VoCCs, and therefore directly and indirectly increases the calcium levels in the cell

Question 22

How is aterilor vasocontrinctions regulated?

Answer 22

Release of noradrenaline, acts on the a1 adrenroectprs to stimulate phsoplipase c, generation of insP3 and realeased Ca2+ from the Er.

Question 23

How is the modulation of neurotransmitter reales stiumatled by G proteins?

Answer 23

Presynaptic u-opioid receptors, and the GBy subunits from the Gc-By triamer interact with VOCCs to reduce entry of calcium.