BCHM 10000 Lecture Notes - Lecture 19: Diisopropyl Fluorophosphate, Covalent Bond, Chymotrypsin

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Insecticides and nerve gases
Organofluorophosphates are used as insecticides and nerve gases and are irreversible
inhibitors of the enzyme acetylcholinesterase
Acetylcholinesterase breaks down acetylcholine in the synaptic cleft of nerve junctions
by hydrolyzing it to acetate and choline
breakdown of acetylcholine attenuates nerve responses
Blocks chrymotopsin and serine
Insecticides and nerve gases
acetylcholinesterase inhibition results in prolonged nerve firing
Atropine is an antidote for insecticide or nerve gas poisoning because it blocks the
binding of acetylcholine to its receptor
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Document Summary

Organofluorophosphates are used as insecticides and nerve gases and are irreversible inhibitors of the enzyme acetylcholinesterase. Acetylcholinesterase breaks down acetylcholine in the synaptic cleft of nerve junctions by hydrolyzing it to acetate and choline. Acetylcholinesterase inhibition results in prolonged nerve firing. Atropine is an antidote for insecticide or nerve gas poisoning because it blocks the binding of acetylcholine to its receptor. Organofluorophosphates are irreversible enzyme inhibitors of many enzymes with active site serine residues. Enzyme is covalently modified after interaction with inhibitor. Modified enzyme is no longer a catalyst. Organofluorophosphates form covalent product with active site serine residues (one residue actually) Mechanism and active site now known to be similar to those of acetylcholinesterase: irreversible inhibitors label chymotrypsin. Diisopropylfluorophosphate (difp) (an organofluorophosphate: the inhibitor becomes covalently bound to active site residues. Suggests what kind of chemistry is involved. Ser 195 is in the enzyme"s active site. Adjacent amino acid residues in active site make ser 195 more reactive.

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