Metabolism, organophosphorus ester

Inhibition of the cholinesterase enzymes depends on blockade of the active site of the enzyme, specifically the site that binds the ester portion of acetylcholine (Fig. 7.48). The organophosphorus compound is thus a pseudosubstrate. However, in the case of some compounds such as the phosphorothionates (parathion and malathion, for example), metabolism is necessary to produce the inhibitor. 

The O-dealkylation of organophosphorus triesters differs from the above reactions in that it involves the dealkylation of an ester rather than an ether. The reaction was first described for the insecticide chlorfenvinphos (Figure 10.2B), but is now known to occur with a wide variety of vinyl, phenyl, phenylvinyl, and naphthyl phosphates and the thionophosphate triesters. At least one phosphonate, O-ethyl O-p-nitrophenyl phenylphosphonate (EPNO), is also metabolized by this mechanism. 

---