Lec2: Drug Targets Flashcards

1
Q

Drugs act by binding to what molecule and inducing what kind of change? What is the exception to this standard?

A

Binds to proteins, and induces conformational change. Exception is binding to DNA –> antimours and antimicrobial drugs.

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2
Q

Cholinergic receptors respond to what neurotransmitter?

A

Acetylcholine.

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3
Q

What is acetylcholine synthesised? (2 sites of action and their respective mediators!) Also indicate the rate-limiting step.

A
  1. Choline uptake by secondary active transporters (mediated by transporters). –> Rate limiting step.
  2. Conversion of choline into acetyl choline by Choline Acetyl Transferase (mediated by enzyme).
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4
Q

Write the equation for acetylcholine synthesis.

A

Choline + Acetyl CoA —(ChAT)—> Acetylcholine + HSCoA

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5
Q

What are the four steps in the release of Acetylcholine into the synaptic cleft?

A
  1. Packaged in vesicles held by Ca2+ sensitive vesicle membrane proteins.
  2. AP arrives.
  3. Voltage dependent Ca2+ channels open
  4. Ca2+ influx stimulates vesicular fusion and therefore NT release.
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6
Q

Write the three basic steps in how receptors operate?

A
  1. Protein recognises specific NT
  2. Conformation change
  3. Activate or inhibit CELL SIGNALLING
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7
Q

What are the 4 families of receptors, and which are slowest and fastest acting?

A
  1. Ligand-gated ion channels (ionotropic) –> fastest
  2. G-protein coupled receptors
  3. Tyrosine kinase/Cytokine receptors
  4. Nuclear/Steroid hormone receptors –> slowest
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8
Q

How fast is a typical transmission by a ligand gated ion channel?

A

Less than 1ms

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9
Q

Are ligand gated ion channels multi-subunit or 1 subunit?

A

Oligomeric (multisubunit).

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10
Q

What are the 3 properties of ligand gated ion channels?

A
  1. Selective for difference ions
  2. Conduct ions through otherwise impermeable cell membrane
  3. Respond to specific ligands
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11
Q

Nicotinic acetylcholine receptors have how many subunits containing how many transmembrane domains each?

A

5 subunits with 4 TM domains each, therefore 20 overall.

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12
Q

What is the acetylcholine binding site on a nicotinic acetylcholine receptor composed of?

A

3 peptide loops on one subunit and 2 peptide loops on a neighbouring subunit.

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13
Q

In order for the channel in a nicotinic acetylcholine receptor to open, where must acetylcholine bind?

A

Two ACh must bind to the ACh binding sites, located between each of the two ALPHA subunits and a neighbouring subunit.

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14
Q

Describe the structure of receptor pore of nACh receptors. Also, what happens if there is a mutation to one of the critical TM2 residues?

A
  1. M2 helices form inwards constriction, but snap open when ACh binds.
  2. TM2 amino acids are highly selective for cations, but when a mutation is induced, they are made selective for anions instead. Therefore, no longer excitatory.
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15
Q

Describe, basically, the GPCR cell-signalling pathway.

A
  1. Ligand bind to receptors
  2. Activates G protein
  3. G protein activates adenylate cyclase
  4. Adenylate cyclase converts ATP to cAMP
  5. cAMP activates Protein Kinase A
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16
Q

For presynaptic receptors, indicate:

  1. The ligand
  2. The function (in some detail)
  3. What happens when the receptor is blocked
A
  1. ACh
  2. Inhibits voltage gated Ca2+ receptors (therefore NEGATIVE FEEDBACK, because ACh binding inhibits ACh release)
  3. Increases ACh release 10-fold
17
Q

What are VAMPs?

A

Ca2+ sensitive vesicle membrane proteins.