Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

116 Chapter 5
Problems
(1) Using para-nitrophenyl acetate as a substrate for chymotrypsin, a rapid
‘burst’ of p-nitrophenol is observed, followed by a slower steady state
release of p-nitrophenol. The amount of product released in the initial
burst is 1 mmol of p-nitrophenol per mmol of enzyme. Explain.
O 2 N
O
O
O 2 N
OH
+
− O
O
(2) Acetylcholinesterase is an esterase enzyme which catalyses the hydrolysis of
acetylcholine (a neurotransmitter) to choline and acetate at nerve synaptic
junctions. Inhibition of acetylcholinesterase is catastrophic and usually
fatal. Given that the enzyme contains a serine catalytic triad, suggest a
mechanism for this enzyme.
O
O
+ acetylcholinesterase
+
NMe 3
O
O − +
NMe 3
HO
acetylcholine
Nerve gas sarin and insecticide parathion both act on this enzyme –
suggest a common mechanism of action. Suggest reasons why parathion is
not so toxic to humans (LD 50 6800 mg kg ) as sarin.
H 3 C
H 3 C
sarin
O
O
P
H 3 C
F
EtO S
P
EtO O
NO 2
parathion
Pyridine aldoximine methiodide is an eVective antidote for organophosphorus
poisonings (used at the time of the Tokyo subway incident in March
1995). Suggest a mechanism for how it works.
CH 3
I − +
N
N OH
pyridine aldoximine
methiodide (PAM)