Session 7 - Signal Transduction

Question 1

What is the full name for a G-protein?

Answer 1

Guanine Nucelotides binding proteins

Question 2

Describe the structure of G-proteins

Answer 2

• Made up of alpha, beta + gamma subunits, with the beta and gamma tightly bound
• Alpha subunit has a nucleotide binding site which binds GTP

Question 3

How are G-proteins activated?

Answer 3

• active receptor has a high affinity for G-protein
• GDP is released and GTP binds
• Alpha subunit dissociates from beta-gamma subunits
• go to interact with receptors

Question 4

How are G-proteins activity terminated?

Answer 4

• GTPase breaks down GTP on alpha subunit
• Affinity between alpha and beta-gamma sub unit increases
• heterotrimer reformed

Question 5

What do Stimulatory Gs interact with and cause?

Answer 5

They stimulate adenylyl cyclase to produce cyclic AMP

Question 6

What do Inhibitory Gi G-proteins interact with and cause?

Answer 6

This decreases adenylyl cyclase levels which results in less cAMP production

Question 7

What do Gq proteins interact with and cause?

Answer 7

They interact with PIP2, to generate IP3 + DAG

Question 8

What do Gt activate and cause? And where are they located?

Answer 8

They activate a phosphodiesterase enzyme that hydrolases GMP -> 5’ GMP
They are located in retinal rod cells

Question 9

Which G-proteins are associated with these adrenergic receptors?
1 - Alpha 1 + Alpha 2
2- Beta 1 + Beta 2

Answer 9

Alpha 1 - Gq (K)
Alpha 2 - Gi (I)
Beta 1 - Gs (S)
Beta 2 - Gs (S)

Question 10

What G-proteins are the following cholinergic receptors associated with:
M1, M2 and M3?

Answer 10

M1 - Gq (Q)
M2 - Gi (I)
M3 - Gq (K)

Question 11

How many of each sub unit does the human genome ave the ability to encode for?

Answer 11

20 alpha
5 Beta
12 Gamma

Question 12

How does cholera toxin effect G-proteins?

Answer 12

• Cholera toxins eliminates the GTPase activity

- Leading to Gs alpha becoming irreversibly activated

Question 13

How does Petussis toxin effect G-proteins?

Answer 13

• It interferes with GDP/GTP exchange on the Gi alpha

- leads to Gi alpha being irreversibly inactivated

Question 14

Name some of the responses that GPCR’s are involved in

Answer 14

Muscle contraction, stimulus secretion coupling, catabolic + anabolic metabolic processes, light, smell and taste perception

Question 15

Describe Adenylyl cyclase and its actions

Answer 15

• integral plasma protein
• activated by Gs, inhibited by Gi
• hydrolases ATP to cAMP
• cAMP interacts with PKA which can phosphorylate other proteins

Question 16

Name some of the physiological effects of Adenylyl cyclase

Answer 16

• Increase in; Glycogensis + gluconeogenesis in liver, lipolysis in adipose
• relaxation of smooth muscle, positive chronotropic effects in the heart

Question 17

What does phospholipase C cause?

Answer 17

• It is an enzyme that hydrolyses PIP2 -> IP3
• Activated by Gq
• IP3 binds to ER receptors
• causes calcium to enter the cytoplasm

Question 18

How is chronotropy regulated in the heart?

Answer 18

• rate at which SAN fires an AP affecetd by Ach release by parasympathetic nerves
• activation of M2 receptors causes an increase in open probability of potassium channels via Gi
• causes hyperpolarisation = -ve chronotropic effect

Question 19

How is inotropy in the heart regulated?

Answer 19

• sympathetic innervation can influence force of contraction
• activation of beta-adrenoreceptors (mostly B1), increases open probability of VOCCs via Gs
• causes a +ve inotropic effect

Question 20

How does arteriolar vasoconstriction occur?

Answer 20

• sympathetic release of NA acts on alpha1 adrenoreceptors
• this stimulates phospholipase C + IP3 production by Gq
• IP3 releases ER calcium + initiates a contractile response