Molecular modifications toxic metabolites

In addition to diffcrence.s in enzyme kinetics contributing to species differences in sensitivity to AChE inhibition, alterations in the AChE enzyme impact its sensitivity to inhibition, Various interspecies, and possibly intraspecies, structural variams of mammalian AChE are synthesized by alternative splicing and posttranslationai modification (Grisaru et ai, 1999 Vidair, 2004). The distribution and molecular forms of AChE in the blood exhibit interspecies differences (Skau, 1985), although the significance to toxicity is not well appreciated, Differences in the physical or molecular properties of AChE influence enzyme and inhibitor interaction. Binding affinity of e parent compound and/or its metabolite for AChE is a major determinant of compound potency and is... 

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