Aging, phosphorylated acetylcholinesterase

This process of aging is believed to be critical in the development of delayed neuropathy, after NTE has been phosphorylated by an OP (see Chapter 10, Section 10.2.4). It is believed that most, if not all, of the B-esterases are sensitive to inhibition by OPs because they, too, have reactive serine at their active sites. It is important to emphasize that the interaction shown in Fignre 2.11 occurs with OPs that contain an oxon group. Phosphorothionates, which contain instead a thion group, do not readily interact in this way. Many OP insecticides are phosphorothionates, but these need to be converted to phosphate (oxon) forms by oxidative desulfuration before inhibition of acetylcholinesterase can proceed to any significant extent (see Section 2.3.2.2). 

Recovery of phosphinylated acetylcholinesterase was also greatly enhanced in our studies of methyl parathion-resistant tobacco budworm larvae (Figure 5). Phosphinylated acetylcholinesterase recovery can be measured without the complication of "aging" which occurs with phosphorylated enzyme (Figure 6). Activity was totally inhibited with 4-nitrophenyl methyl(phenyl)phosphinate. Excess inhibitor was removed by solid phase extraction and recovering activity at 30°C was monitored in aliquots. We have confirmed this insensitivity with individual heads of adults from these strains and we are investigating inheritance of this trait. 

Wallace. K., and Herzberg, U. (1988). Reactivation and aging of phosphorylated brain acetylcholinesterase from fish and rodents. Toxicol, Appl. Pharmacol. 92, 307-314. 

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