ENZYME KINETICS Flashcards

1
Q

What is anticholinesterase?

A

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

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2
Q

Name an inhibitor of cyclo-oxygenase

A

Aspirin or ibuprofen

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3
Q

What is the target of viagra/sildenafil?

A

Phosphodiesterase type 5

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4
Q

Name an ACE inhibitor

A

Captopril

ACE = Angiotensis converting enzyme

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5
Q

Name 4 enzymes as drug targets

A
  1. Acetylcholinesterase
  2. Cyclo-oxygenase
  3. PDE type 5
  4. ACE
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6
Q

Describe and explain the Michaelis-Menten kinetics graph

A

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.
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7
Q

What is the Vmax?

A

The maximum rate of reaction

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8
Q

What is the km?

A
  • 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.
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9
Q

Describe the different types of reversible enzyme inhibitors

A
  1. Competitive
  2. Non- competitive
  3. Uncompetitive
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10
Q

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

A

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

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11
Q

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

A
  • No effect on km

- Reduces vmax

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12
Q

How does competitive antagonism affect the km and vmax?

A
  • Increases the km

- Does not affect the vmax

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13
Q

How does uncompetitive inhibition affect the km and vmax?

A
  • Decrease both km and vmax.
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14
Q

What is the difference between reversible and irreversible inhibitors?

A

irreversible inhibitors bind covalently, reversible inhibitors do not.

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15
Q

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

A

the CFTR

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

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16
Q

Name 2 types of the drugs that target CFTRs

A
  • SSRI’s (Serotonin reuptake inhibitors) aka Prozac

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

17
Q

Describe the receptor activation equation of agonists

A

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

18
Q

Describe the receptor activation equation of antagonists

A

k +1

A + R ———> AR + no response

19
Q

Describe the difference between affinity and efficacy.

A

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.

20
Q

Describe the difference between a partial and inverse agonist.

A

Partial agonists: substance with intermediate levels of activation

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

21
Q

What is constitutive activation?

A

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

22
Q

What do allosteric modulators do?

A
  1. They increase the efficacy and affinity of orthosteric agonists
  2. They may have direct agonist efficacy themselves.
23
Q

What are the advantages of allosteric modulators?

A
  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.
24
Q

What does this statement mean?

‘Drug A is more potent than drug B’

A
  • 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.

25
Q

What does equipotent mean?

A

Having the same potencies

look at the graph in book

26
Q

Describe the law of mass action

A

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

27
Q

What is Kd?

A
  • 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.
28
Q

What is the Hill Langmuir equation?

A

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

(look at book for more notes)

29
Q

What is the hill langmuir equation used for?

A

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

30
Q

What is a saturation binding site study?

A
  • It is using a radioligand at equilibrium to measure the affinity of receptors.
31
Q

Name 2 radioligands

A

Cyanopindolol = Binds to beta adrenoreceptors in cardiac cells

Muscimol/flumazenil = binds to GABAa.

(look at notes for rectangular hyperbola)

32
Q

What is ic50?

A
  • 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
33
Q

What is the cheng preusoff equation

A

Ki = ic50/1+(Aconc/KD)