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Biochemistry · Enzyme inhibition: organophosphate poisoning
Sample itemA farmer after spraying a pesticide has miosis, salivation, bradycardia and fasciculations, and red cell cholinesterase is low. What is the mechanism of enzyme inhibition?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
C. Irreversible phosphorylation of a serine at the active site of acetylcholinesterase
Organophosphates phosphorylate the active-site serine of acetylcholinesterase, so acetylcholine accumulates at muscarinic and nicotinic synapses. The bond becomes irreversible after ageing, so oximes such as pralidoxime work best when given early, with atropine to block muscarinic effects. Carbamates inhibit in a reversible, carbamylating way.
Option by option
A. Reversible competitive binding that is overcome by excess substrate
Reversible competitive inhibition describes drugs such as edrophonium, not organophosphates.
B. Binding of an allosteric inhibitor that changes enzyme shape
Allosteric inhibition is not the mechanism, since the inhibitor attacks the catalytic serine.
C. Irreversible phosphorylation of a serine at the active site of acetylcholinesterase (correct)
Correct. Covalent phosphorylation of the active-site serine inhibits irreversibly.
D. Reduced synthesis of acetylcholinesterase by transcriptional repression
Organophosphates do not act by repressing transcription of the enzyme.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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