Enzymes as drug targets Flashcards
1
Q
Enzymes
A
Protien molecules that catalyse a specific reaction and they are unchanged by they reaction they are in
2
Q
Lock and key model
A
- Enzyme bind with free substrate at the active site due to 3D complementory specific structure
- Sunstrate bind reversibly at the active site via non-covalent interaction
- Reaction takes place and enzyme product complex forms
- Product formed less strongly bound so are released by the enzyme
3
Q
Binding in lock and key way
A
- Hydrophoic region binds to the hydrophobic region of enzyme
- Positive region of the substrate binds to the negative region of the enzyme
4
Q
What does the enzyme do?
A
- Lowers the gibbs activation energy therefor reaction is faster
5
Q
Michaelis menten equation
A
- Rate = Vmax[S]/Km+[S]
- Velocity of the rate of enzyme catalysed activity increases in non-linear way
- K2 multiplied by total conc of enzyme
6
Q
Km
A
K1+K2/K1
7
Q
Vmax
A
- K2[E]0
- Rate is independant of [S]
- [ES] = [E]0
- Increase substrate but doesn’t change Vmax saturated
- maximum rate that the enzyme can achieve
8
Q
Small substrate conc
A
- K2[E]0S/Km
9
Q
What is Km
A
- Concentration pf S at which the reaction is half maxiumum (Vmax/2)
- Depends how tight the binding of substrate
10
Q
Enzyme inhibitors
A
- Binding covalently to enzyme or highly stable non-covalent bond association
- Electrophilic reagent - alkylating
- Metal chelators EDTA
- Usually needs to be specific they have to bind to one enzyme
11
Q
Irreversible enzyme inhibitors
A
- More selective for the target which initally binds reversibly then the molecule is held long enough
- Mild reactive electrophilic groups used
12
Q
What is the stregth of the the inhibitor dependant on
A
- Drug concentration and time after administration
13
Q
Reversible enzyme inhibitors
A
- Non-covalent diffuse in and out of the enzyme.
- Once bound can be unbount
14
Q
3 types of competitive inhibitors
A
- Enzyme reversible inhibitors are competitive and they bind to the same site of the substrate and prevent the substrate from binding
- If enough substrate is present it will out-compete the inhibitor and saturate the enzyme
- Increase the Km the higher th substrate conc to saturate the enzyme when the inhibitor is present
15
Q
Reversible inhibitor effects
A
- Do not effect the Vmax and they increase the Km
- Lower the Ki the tighter the binding so it is a more effective inhibitor
16
Q
Reversible uncompetitive
A
- Decreases the Vmax and decreases the Km
- This increasing substrate concentration makes the inhibitor more effective binds to ES
- Km decreased apparent affinity of E and S is increased pulling the equalibrium for ES formation to the right
17
Q
Mixed inhibitor
A
- Combination of competitive and non-competitive
- Always decrease Vmax, but can increase or decrease Km, depending on the relative values of KI and KI
18
Q
Non-competitive inhibitor
A
- Decrease Vmax and do NOT affect Km,
cross-over point between the two types of mixed inhibition is rare
19
Q
Non-competitive inhibitor
A
- Decrease Vmax and do NOT affect Km,
cross-over point between the two types of mixed inhibition is rare
20
Q
Penicillian
A
- Irreversible enzyme inhibitors which are specific to bacterial enzymes used to build up the bacterial wall
- Beta lactam antibiotics acylate the enzyme to due to the beta lactem ring
21
Q
Suicide inactivators
A
- Irreversible covalent inhibitors as the drug molecule completely inactivates the enzyme molecule and it is lost in the process
22
Q
Reversible inhibitor
A
- Non-covalent and diffuses in and out of the enzyme
- Once bound another may be able to bind only enzyme substrate complex formed for catalytic activity
