Post on 18-Jan-2016
Chapter 6.3: Enzyme Inhibition
CHEM 7784
Biochemistry
Professor Bensley
CHAPTER 6.3 Enzyme Inhibition
– Various types of enzyme inhibition
Today’s Objectives: (To learn and understand the)
Enzyme Inhibition
Inhibitors are compounds that decrease enzyme’s activity
• Irreversible inhibitors (inactivators) react with the enzyme
• Reversible inhibitors bind to, and can dissociate from the enzyme
• Reversible inhibitor can bind:
– To the free enzyme and prevent the binding of the substrate
– To the enzyme-substrate complex and prevent the reaction
Competitive Inhibition
Lines intersect at the y-axis
Uncompetitive InhibitionLines are parallel
Mixed InhibitionLines intersect left of the y-axis
MAKE SURE YOU DISTINGUISH THIS FROM NON-COMPETITIVE INHIBITION!!!!
Viagra (Sildenafil Citrate)
Medicinal Inhibitor Example
Irreversible Inhibitors
H3C O P
O
S C
C
H
O
O CH2CH3
C O CH2CH3
O
S
CH3
CH2
H C
CH3
O
CH3
P
F
O
O C
CH3
H
CH3
Diisopropyl fluorophosphate(nerve gas)
H3C O P
O
S
S
CH3
NO2
parathion
malathion
•Organophosphates•Inhibit serine hydrolases•Acetylcholinesterase inhibitors
Kinetics of Multisubstrate Reactions
E + A + B <-> E + P + Q
• Sequential Reactions (Ternary Complex
formed)
a) Random
b) Ordered
• Ping-Pong Reactions
Sequential Reactions
E EA (EAB) (EPQ) EQ E
A B P Q
AB PQ
A B
E
EA
EB
(EAB)(EPQ)
P Q
EQ
EP
E
Ordered
Random
Ping-Pong Reactions
E (EA)(FP) (F) (FB)(EQ) E
A BP Q
•In Ping-Pong rxns first product released before second substrate binds
•When E binds A, E changes to F
•When F binds B, F changes back to E
Lineweaver-Burke Plot of Multisubstrate Reactions
Increasing [B]
Increasing [B]
Sequential Ping-Pong
Vmax doesn’t changeKm changes
Both Vmax & Km change
1/Vo
1/[S]
1/Vo
1/[S]