Which amino acid is targeted by diisopropyl fluorophosphate in the inhibition of acetylcholinesterase?

• A. Cysteine
• B. Histidine
• C. Serine
• D. Tyrosine

Answer: (C)

Diisopropyl fluorophosphate (DFP) is a potent organophosphate that irreversibly inhibits the enzyme acetylcholinesterase by specifically targeting a serine residue in the enzyme's active site. The active site of acetylcholinesterase has a catalytic triad, which includes serine, histidine, and aspartate. Serine plays a crucial role in the enzymatic reaction that hydrolyzes acetylcholine, leading to the termination of its action at the neuromuscular junction and synapses in the central nervous system.

When DFP interacts with acetylcholinesterase, it forms a stable bond with the hydroxyl group of the serine residue, thus preventing the enzyme from functioning effectively. This inhibition leads to an accumulation of acetylcholine, causing prolonged stimulation of the postsynaptic receptors, which can lead to symptoms such as muscle twitching, paralysis, and potentially respiratory failure if left untreated.

Understanding the mechanism of DFP's action highlights the critical role of serine in enzymatic activity and the importance of acetylcholinesterase in neurotransmission.