ENZYME KINETICS

Question 1

What is anticholinesterase?

Answer 1

A drug that targets acetylcholinesterase (the enzyme that makes Ach)

Question 2

Name an inhibitor of cyclo-oxygenase

Answer 2

Aspirin or ibuprofen

Question 3

What is the target of viagra/sildenafil?

Answer 3

Phosphodiesterase type 5

Question 4

Name an ACE inhibitor

Answer 4

Captopril

ACE = Angiotensis converting enzyme

Question 5

Name 4 enzymes as drug targets

Answer 5

1. Acetylcholinesterase
2. Cyclo-oxygenase
3. PDE type 5
4. ACE

Question 6

Describe and explain the Michaelis-Menten kinetics graph

Answer 6

Description:

• Rate of reaction vs substrate concentration
• Shows the vmax and km

Explanation:

• The rate of reaction increases with increasing substrate
• The graph starts off linear
• Graph eventually reaches a plateau when all active sites are saturated with substrates so the ROR does not increase anymore.

Question 7

What is the Vmax?

Answer 7

The maximum rate of reaction

Question 8

What is the km?

Answer 8

• The concentration of a substrate required to achieve half of the maximum rate of reaction.
• A measure of how tightly the substrate binds to the enzyme (the lower the number the tighter the binding.

Question 9

Describe the different types of reversible enzyme inhibitors

Answer 9

1. Competitive
2. Non- competitive
3. Uncompetitive

Question 10

What is the difference between:
competitive antagonsim
non-competitive antagonism
uncompetitive antagosim

Answer 10

Competitive: Binds to the orthosteric site

Non- competitive: Binds to a diff site on the enzyme +
Can bind with or without the actual substrate of the enzyme

Uncompetitive: Also binds to a diff site on the enzyme, but ONLY binds when a substrate is bound to the enzyme

Question 11

how does non-competitive antagonism affect the km and vmax?

Answer 11

• No effect on km

- Reduces vmax

Question 12

How does competitive antagonism affect the km and vmax?

Answer 12

• Increases the km

- Does not affect the vmax

Question 13

How does uncompetitive inhibition affect the km and vmax?

Answer 13

• Decrease both km and vmax.

Question 14

What is the difference between reversible and irreversible inhibitors?

Answer 14

irreversible inhibitors bind covalently, reversible inhibitors do not.

Question 15

Describe a transporter that can be targeted by drugs and it’s roles

Answer 15

the CFTR

roles: Uptaking neurotransmitters into vesicles and recycling neurotransmitters at a synapse

Question 16

Name 2 types of the drugs that target CFTRs

Answer 16

• SSRI’s (Serotonin reuptake inhibitors) aka Prozac

- SNRI (Dual serotonin/nor adrenalise reuptake inhibitors) aka Cymbalta

Question 17

Describe the receptor activation equation of agonists

Answer 17

K off
ASSOCIATION RATE
k + 1 m-1 min-1
A + R ——————–> AR + Response
(drug A) (Receptor)

Question 18

Describe the receptor activation equation of antagonists

Answer 18

k +1

A + R ———> AR + no response

Question 19

Describe the difference between affinity and efficacy.

Answer 19

Affinity: How well the drug binds to the receptor.
Efficacy: If the drug acc produces a downstream response.

Side note: Diff drugs can have diff efficacies.

Question 20

Describe the difference between a partial and inverse agonist.

Answer 20

Partial agonists: substance with intermediate levels of activation

Inverse agonists: substance that binds to the receptor and stop constitutive activation

Question 21

What is constitutive activation?

Answer 21

When the receptor spontaneously switches from active –> inactive –> active etc without an agonist being bound.

Question 22

What do allosteric modulators do?

Answer 22

1. They increase the efficacy and affinity of orthosteric agonists
2. They may have direct agonist efficacy themselves.

Question 23

What are the advantages of allosteric modulators?

Answer 23

1. Positive allosteric modulators potentiate effects of endogenous agonist, This is safer than always using an agonist because:
   - That could lead to too much receptor activation or desensitisation.

Question 24

What does this statement mean?

‘Drug A is more potent than drug B’

Answer 24

• It means that drug A has the same efficacy as drug B, but A requires less concentration to achieve the same effect.

Side note: Look at the graph in my book notes.

Question 25

What does equipotent mean?

Answer 25

Having the same potencies

look at the graph in book

Question 26

Describe the law of mass action

Answer 26

The rate of chemical reaction is proportional to the total of the concentration of REACTANTS.

Question 27

What is Kd?

Answer 27

• the CONCENTRATION of a drug required for 50% occupancy.
• Kd(= k -1/ k +1)
• The higher the affinity of the ligand, the LOWER the kD.

Question 28

What is the Hill Langmuir equation?

Answer 28

[AR] [A] conc of drug
————– = ————
[Rtot] [Kd] + [A]

(look at book for more notes)

Question 29

What is the hill langmuir equation used for?

Answer 29

It is used to calculate how receptor occupancy changes with drug concentration.

Question 30

What is a saturation binding site study?

Answer 30

• It is using a radioligand at equilibrium to measure the affinity of receptors.

Question 31

Name 2 radioligands

Answer 31

Cyanopindolol = Binds to beta adrenoreceptors in cardiac cells

Muscimol/flumazenil = binds to GABAa.

(look at notes for rectangular hyperbola)

Question 32

What is ic50?

Answer 32

• The concentration of an inhibitor required to inhibit radioligand binding to the receptor by 50%
• ic50 depends on the radioligand used (obvs)
• Converted to radioligand independent value ki using the cheng-prusoff equation
• ki is always less than ic50

Question 33

What is the cheng preusoff equation

Answer 33

Ki = ic50/1+(Aconc/KD)