Some genetic interventions in organophosphates and other insecticides metabolism

Organophosphates represent a very large class of insecticides used in the last decades, together with carbamates and pyrethroids. They act on the nervous system, with various effects, mostly cholinergic signs, but for some compounds, noncholinergic ones. Their metabolism involves esterase enzymes, including here the group of aliesterases (e.g. carboxylesterases), but also arylesterases (e.g. paraoxonase - PON1) and cholinesterases (e.g. butyrcholinesterase), both with a smaller contribution, compared to the first mentioned class. These enzymes act on a specific substrate, although in some cases interchangeable substrates were reported. The content of esterases in various species is different and inside of the individual, the site of action is particular for each enzyme. A typical way of detoxification through reactions of hydrolysis was reported for carboxylesterases, resulting products which are more polar and more easily to be excretable. Two of human carboxylesterases, hCE-1 and hiCE-2 (hCE-2) and their mammalian homologous are known to be involved in various xenobiotic detoxification processes, through this mechanism. When some insecticides, such as malathion-type compounds, are bioactivated, the further detoxification is performed by the paraoxonase (PON1), but also by the albumin and butyrcholinesterase. This paper aims to debate the main enzymes involved in the metabolism of organophosphates, carbamates and other insecticides, discussing comparative genetic aspects in animals and humans.