Biochemical Basis Of Therapy

Question 1

General structure of ligand gated ion channel receptors:

Answer 1

Consist of separate glycoprotein subunits:
- Allows rapid changes in permeability of membrane to certain ions
- Rapidly alters membrane potential

Question 2

General function of ligand-gated ion channel receptors:

Answer 2

Hydrophilic signalling molecule

Steps:
1. Ligand binds to the receptor, channel opens
2. Ions flow through passively
3. Triggers signalling pathway

Question 3

General structure of G-protein-coupled receptors:

Answer 3

G protein:
- Peripheral membrane protein
- 3 polypeptide subunits
- Alpha subunit holds GTP or GDP

Receptor:
- Integral membrane protein
- Single polypeptide with extracellular NH2 terminal and Intracellular COOH terminal

Question 4

Function of G-protein-coupled receptors:

Answer 4

Sympathetic response

Turning signal on:
- Agonist activates G-coupled receptor
- Alpha subunit leaves G-protein
- GDP exchanged for GTP
- Triggers other proteins in signalling pathway

Turning signal off:
- Alpha subunit hydrolyses GTP -> GDP
- Deactivating G-protein
- Alpha subunit recombines with Beta Gamma subunit

No signalling:
- Alpha subunit binding site occupied by GDP

Question 5

Example of G-protein coupled receptor (endogenous ligand agonist)

Answer 5

Ligand-gated ion channels

Nicotine acetylcholine receptor

Permeable to Na+, K+ and Ca2+

Agonists: Acetlycholine, Nicotine, Varenicline (partial)

Varenicline inhibits binding of nicotine, easing nicotine withdrawal symptoms

Question 6

Example of G-protein coupled receptor (transduction mechanism and 2nd messengers)

Answer 6

Kinase linked receptors

Steps:
1. Ligand binds
2. Receptor dimerises
3. Cross phosphorylation takes place
4. Signalling pathways triggered which activates 2nd messenger

Question 7

General structure of kinase-linked and nuclear receptors:

Answer 7

Kinase linked:
- Located in plasma membrane
- Hydrophilic protein mediator

Nuclear receptors:
- Found in nucleus of target cell
- Bound by steroid hormones
- 2 domains, ligand binding domain and DNA binding domain

Question 8

General function of kinase-linked and nuclear receptors:

Answer 8

Kinase-linked:
- Activates multiple pathways (second messengers)
- Enzymes phosphorylate other molecules
- Can’t phosphors late their own tyrosine side chains - they dimerise and cross-phosphorylate

Nuclear receptors:
- Activation causes transcription of key proteins

Question 9

Year 1 core drugs

Answer 9

•Amlodipine
•Salbutamol
•Theophylline
•Insulin
•Thiazides
•Ibuprofen
•SSRIs
•Sodium valproate