Enzymes as drug targets

Question 1

Enzymes

Answer 1

Protien molecules that catalyse a specific reaction and they are unchanged by they reaction they are in

Question 2

Lock and key model

Answer 2

• 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

Question 3

Binding in lock and key way

Answer 3

• Hydrophoic region binds to the hydrophobic region of enzyme
• Positive region of the substrate binds to the negative region of the enzyme

Question 4

What does the enzyme do?

Answer 4

• Lowers the gibbs activation energy therefor reaction is faster

Question 5

Michaelis menten equation

Answer 5

• 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

Question 6

Km

Answer 6

K1+K2/K1

Question 7

Vmax

Answer 7

• 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

Question 8

Small substrate conc

Answer 8

• K2[E]0S/Km

Question 9

What is Km

Answer 9

• Concentration pf S at which the reaction is half maxiumum (Vmax/2)
• Depends how tight the binding of substrate

Question 10

Enzyme inhibitors

Answer 10

• 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

Question 11

Irreversible enzyme inhibitors

Answer 11

• More selective for the target which initally binds reversibly then the molecule is held long enough
• Mild reactive electrophilic groups used

Question 12

What is the stregth of the the inhibitor dependant on

Answer 12

• Drug concentration and time after administration

Question 13

Reversible enzyme inhibitors

Answer 13

• Non-covalent diffuse in and out of the enzyme.
• Once bound can be unbount

Question 14

3 types of competitive inhibitors

Answer 14

• 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

Question 15

Reversible inhibitor effects

Answer 15

• Do not effect the Vmax and they increase the Km
• Lower the Ki the tighter the binding so it is a more effective inhibitor

Question 16

Reversible uncompetitive

Answer 16

• 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

Question 17

Mixed inhibitor

Answer 17

• Combination of competitive and non-competitive
• Always decrease Vmax, but can increase or decrease Km, depending on the relative values of KI and KI

Question 18

Non-competitive inhibitor

Answer 18

• Decrease Vmax and do NOT affect Km,
  cross-over point between the two types of mixed inhibition is rare

Question 19

Non-competitive inhibitor

Answer 19

• Decrease Vmax and do NOT affect Km,
  cross-over point between the two types of mixed inhibition is rare

Question 20

Penicillian

Answer 20

• 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

Question 21

Suicide inactivators

Answer 21

• Irreversible covalent inhibitors as the drug molecule completely inactivates the enzyme molecule and it is lost in the process

Question 22

Reversible inhibitor

Answer 22

• 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