THE AGEING AND DE-ALKYLATION OF ALKYL ALKYLPHOSPHONOCHOLINESTERASES
Porton technical paper
CHEMICAL DEFENCE EXPERIMENTAL ESTABLISHMENT PORTON DOWN (UNITED KINGDOM)
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A study has been made of the de-alkylation and ageing of several alkyl methylphosphono-acetyl cholinesterases. The rate of de-alkylation was found to vary with the structure of the alkyl group. Ageing, the conversion of the inhibited enzyme into a non-reactivatable form, was found to differ from de-alkylation in a number of instances, and showed a further variation with the oxime used as reactivator. This difference is attributed either to the inability to define ageing in precise chemical terms, or to the involvement of a two-step process. The amount of enzyme activity restored by oximes was always less than that expected from the residual under alkylated enzyme. The important factor in the failure of oxime therapy for nerve gas poisoning is considered to be the fraction of enzyme activity that can be restored under practical conditions. Comparison of rates of half-lives of ageing is not considered satisfactory. The inability of oximes to restore an appreciable amount of the activity of pinacolyl methyl phosphono-acetylcholinesterase GD-inhibited enzyme is attributed to its rapid de-alkylation.
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