Question

Which ONE of the following is an example of an irreversible inhibitor of acetylcholinesterase enzyme?

• A. Malathion
• B. Donepezil
• C. Carbofuran
• D. Aldicarb

Hint:

AChE Inhibitors:
Irreversible = Organophosphates (Malathion, Parathion, Sarin, DFP).
Reversible = Donepezil, Edrophonium, Neostigmine.

Answer 1

The Correct Option is A

Step 1: Understanding the Concept:
Neurotoxic anticholinesterases are divided into reversible carbamate/piperidine inhibitors and irreversible covalent organophosphorus compounds.
Key Formula or Approach:
\[ \text{AChE-Ser-OH} + \text{Organophosphate} \longrightarrow \text{AChE-Ser-O-Phosphoryl (Irreversible Aging)} \]

Step 2: Detailed Explanation:
Evaluating acetylcholinesterase (AChE) inhibitors:
1. Malathion (Organophosphate): Metabolized in vivo to malaoxon, which covalently phosphorylates the active-site catalytic serine hydroxyl group of AChE. The phosphorylated enzyme undergoes an 'aging' dealkylation reaction that renders the covalent inhibition permanent and irreversible.
2. Donepezil: Reversible, non-covalent competitive AChE inhibitor used in Alzheimer's.
3. Carbofuran Aldicarb: Carbamates that form carbamoylated enzyme intermediates which spontaneously hydrolyze over hours (reversible pseudo-irreversible).

Step 3: Final Answer:
Therefore, Malathion is an irreversible inhibitor of acetylcholinesterase, corresponding to option (A).