Ageing of acetylcholine esterase

 

Ageing of acetylcholine esterase

·         Acetylcholine is the endogenous cholinergic neurotransmitter.

·         Acetylcholine esterase is an enzyme present in the milieu of the synaptic cleft that degrades acetylcholine into acetyl and choline and terminates post synaptic muscarinic receptor stimulation.

·         Acetylcholine esterase inhibitors bind with acetylcholine esterase and prevent degradation of acetylcholine. So cholinergic transmission increases.

·         Acetylcholine inhibitors are of two types-Reversible and Irreversible

·         With reversible acetylcholine inhibitors, the enzyme is regenerated in reasonable time. So cholinergic stimulation is of short duration and shows time bound recovery

·         With irreversible acetylcholine inhibitors, the enzyme is regenerated very slowly. So cholinergic stimulation is prolonged and recovery depends upon synthesis of fresh enzyme.

·         Therefore, poisoning with irreversible inhibitors is much more dangerous than reversible inhibitors.

·         Among the irreversible inhibitors, the organophosphates may lose one of its alkyl groups and the enzyme-organophosphate becomes completely resistant to hydrolysis. The enzyme is not regenerated at all. This is known as “Ageing” of the enzyme. Recovery completely depends upon synthesis of fresh enzyme. Oximes, if administered as antidote, must be administered promptly because after “ageing”, even oximes cannot regenerate the enzymes.