ICPP 6 Biolgical Signalling Molecules + Major Classes of Drug Targets + Signal Trasduction 1

Question 1

Drug target classes

Answer 1

RITE

Receptors
Ion channels
Transporters
Enzymes

Question 2

What are drugs acting on ion channels usually termed?

Answer 2

Blockers

Question 3

What are drugs acting on transporters or enzymes usually termed?

Answer 3

Inhibitors

Question 4

Categorisations of receptors

Answer 4

K(L)ING
Kinase linked receptors
Ion channels (Ligand gated)
Nuclear
G-protein coupled receptor

Question 5

Function of transporters

Answer 5

• setting up and maintaining electrochemical gradients
• regulate cell volume + pH
• transport of metabolites

Question 6

What binds to kinases?

Answer 6

Peptides + proteins
Hormones
Growth factors
Cytokines

Question 7

What are the 3 superfamilies of cell surface receptors?

Answer 7

• G protein coupled receptor
• Ligand gated ion channels
• Receptors with intrinsic enzymatic activity e.g. receptor tyrosine kinases

Question 8

What are G protein coupled receptors and what do they do?

Answer 8

A superfamily of receptors with an enormous diversity of cellular functions
- alter the activities of effectors

Question 9

Structure of GPCRs

Answer 9

Single polypeptide chain
7-transmembrane spanning regions
Extracellular N terminal
Intracellular C terminal

Question 10

Two regions of GPCRs for ligand binding site

Answer 10

• within in 7 transmembrane domains
• the N terminal region

Question 11

What does G protein stand for?

Answer 11

Guanine nucleotide binding protein

Question 12

Structure of G proteins

Answer 12

Alpha subunit
Beta + gamma subunit
Heterotrimeric: 3 subunits

Question 13

Describe a G protein under basal resting conditions (inactive/off state)

Answer 13

GDP is bound to a subunit
In its heterotrimeric form

Question 14

Outline the effects of ligand binding to a GPCR

Answer 14

• ligand binds to GPCR + activates it
• interaction with G protein&raquo_space; G protein activated
• GTP exchange for GDP on a subunit
  exchange NOT phosphorylation
• a-B complex lose affinity + dissociates&raquo_space; a(GTP) + By
• interact with effector proteins

Question 15

Describe the affinity of GPCR for the G protein after the guanine nucleotide exchange

Answer 15

• the binding of GTP to a subunit decreases the affinity of the receptor for the aBy subunits
• subunits dissociate + interact with effectors

Question 16

Outline how the GPCR cycle is reactivated after subunit interactions with effectors

Answer 16

• subunit interaction with effectors lasts until GTP is hydrolyses back to GDP by GTPase
  hydrolysis NOT exchange
  -affinity of subunits increase
• inactive heterotrimeric complex forms again

Question 17

3 G protein types + their functions

Answer 17

Gas - stimulates adenylyl cyclase
Gsi - inhibits adenylyl cyclase
Gaq - stimulates phospholipase C

Question 18

Function of Gas

Answer 18

Stimulates adenylyl cyclase

Question 19

Function of Gai

Answer 19

Inhibits adenylyl cyclase

Question 20

Function of Gaq

Answer 20

Stimulates phospholipase C

Question 21

What can interfere with G protein function

Answer 21

Cholera toxin - CTx
Pertussis toxin - PTx

Question 22

Action of CTX

Answer 22

Prevents termination of GPCR + G protein activation

Gs-signally chronically active/on

Question 23

Action of PTx

Answer 23

Uncouples GPCRs
Prevents activation
GI-signally chronically inactive/off

Question 24

What is QISS QIQ?

Answer 24

The types of G proteins which correspond to adrenorecptors QISS or muscarinic QIQ

Q - alpha 1
I - alpha 2
S - beta 1
S - beta 2

Q - muscarinic 1
I - muscarinic 2
Q - muscarinic 3