Lecture 1

Question 1

Describe the process of Ach Synthesis and release. What is the rate limiting step in in Ach synthesis

Answer 1

Choline (obtained from diet) is taken up into the synaptic terminal through the Choline/Na+ transporter (choline transporter - the rate limiting step in Ach Synthesis). Then the enzyme ChAT is involved in converting the choline to Ach. The Ach is then stored in synaptic vesicles by the vesicular Ach transporter. The vesicles then fuse with the membrane by Ca+ rushing into the nerve.

Question 2

Describe the the structure of the nAchR

Answer 2

5 subunits, each subunit has 4 transmembrane domains. Each Ach binding site binds to 3 peptide loops on 1 subunit and 2 peptide loops on the adjacent subunit. The Ach binds to 1 one of the 2 alpha subunits, and you need to have 2 Ach molecules binding to open the channel. When both are bound, the five M2 helices which are kinked inwards halfway through the membrane open.

Question 3

Describe how medicines can work on G-protein coupled receptors and give an example.

Answer 3

Medicines can work on G-protein coupled receptors by either acting as agonists or agonists or antagonists. For example, medicines that block the pre-synaptic receptor M2 receptor, which inhibits calcium channels, lead to huge increases in neurotransmitter release.

Question 4

What tyrosine kinase receptors? Explain the role of VEGFR2.

Answer 4

Receptor functions as an enzyme that transfers phosphate from ATP to tyrosine residues on intracellular target proteins.

VEGR2 - ligand stimulated dimerisation - phosphorylates the tyrosine residues in the cytoplasmic domain, downstream EKR will be activated, leading to increased gene transcription and ultimately a increase endothelial function.