ENZYME KINETICS Flashcards
What is anticholinesterase?
A drug that targets acetylcholinesterase (the enzyme that makes Ach)
Name an inhibitor of cyclo-oxygenase
Aspirin or ibuprofen
What is the target of viagra/sildenafil?
Phosphodiesterase type 5
Name an ACE inhibitor
Captopril
ACE = Angiotensis converting enzyme
Name 4 enzymes as drug targets
- Acetylcholinesterase
- Cyclo-oxygenase
- PDE type 5
- ACE
Describe and explain the Michaelis-Menten kinetics graph
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.
What is the Vmax?
The maximum rate of reaction
What is the km?
- 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.
Describe the different types of reversible enzyme inhibitors
- Competitive
- Non- competitive
- Uncompetitive
What is the difference between:
competitive antagonsim
non-competitive antagonism
uncompetitive antagosim
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
how does non-competitive antagonism affect the km and vmax?
- No effect on km
- Reduces vmax
How does competitive antagonism affect the km and vmax?
- Increases the km
- Does not affect the vmax
How does uncompetitive inhibition affect the km and vmax?
- Decrease both km and vmax.
What is the difference between reversible and irreversible inhibitors?
irreversible inhibitors bind covalently, reversible inhibitors do not.
Describe a transporter that can be targeted by drugs and it’s roles
the CFTR
roles: Uptaking neurotransmitters into vesicles and recycling neurotransmitters at a synapse
Name 2 types of the drugs that target CFTRs
- SSRI’s (Serotonin reuptake inhibitors) aka Prozac
- SNRI (Dual serotonin/nor adrenalise reuptake inhibitors) aka Cymbalta
Describe the receptor activation equation of agonists
K off
ASSOCIATION RATE
k + 1 m-1 min-1
A + R ——————–> AR + Response
(drug A) (Receptor)
Describe the receptor activation equation of antagonists
k +1
A + R ———> AR + no response
Describe the difference between affinity and efficacy.
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.
Describe the difference between a partial and inverse agonist.
Partial agonists: substance with intermediate levels of activation
Inverse agonists: substance that binds to the receptor and stop constitutive activation
What is constitutive activation?
When the receptor spontaneously switches from active –> inactive –> active etc without an agonist being bound.
What do allosteric modulators do?
- They increase the efficacy and affinity of orthosteric agonists
- They may have direct agonist efficacy themselves.
What are the advantages of allosteric modulators?
- 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.
What does this statement mean?
‘Drug A is more potent than drug B’
- 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.
What does equipotent mean?
Having the same potencies
look at the graph in book
Describe the law of mass action
The rate of chemical reaction is proportional to the total of the concentration of REACTANTS.
What is Kd?
- 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.
What is the Hill Langmuir equation?
[AR] [A] conc of drug
————– = ————
[Rtot] [Kd] + [A]
(look at book for more notes)
What is the hill langmuir equation used for?
It is used to calculate how receptor occupancy changes with drug concentration.
What is a saturation binding site study?
- It is using a radioligand at equilibrium to measure the affinity of receptors.
Name 2 radioligands
Cyanopindolol = Binds to beta adrenoreceptors in cardiac cells
Muscimol/flumazenil = binds to GABAa.
(look at notes for rectangular hyperbola)
What is ic50?
- 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
What is the cheng preusoff equation
Ki = ic50/1+(Aconc/KD)
