Phorate (O,O-diethyl S-ethylthiomethyl phosphorodithioate) is a toxic organophosphate anticholinesterase insecticide. Organophosphate insecticides can cause respiratory depression and seizures due to acetylcholinesterase inhibition. Inhibited acetylcholinesterase cannot break down the neurotransmitter, acetylcholine; thus, causing an overload of acetylcholine in synapses and neuromuscular junctions. Oxidative desulfuration, from metabolism by cytochrome P450 enzymes, converts the P=S phosphorothionate group on phorate to the P=O oxon group. Electrophilic oxon groups attack the active site on acetylcholinesterase, inducing the toxicity associated with organophosphate insecticides. Possible further bioactivation to phorate-oxon-sulfoxide and phorate-oxon-sulfone near the site of acetylcholinesterase in the brain may increase acetylcholinesterase inhibitory potency. Adult male Sprague-Dawley rat brain and liver microsomes were used to determine the proportions of the phorate metabolites formed through bioactivation. Phorate-sulfoxide was produced in much greater proportion than any other metabolite, which may contribute to the delay observed in phorate toxicity as it takes longer to produce phorate-oxon, phorate-oxon-sulfoxide, or phorate-oxon-sulfone metabolites.
| Identifer | oai:union.ndltd.org:MSSTATE/oai:scholarsjunction.msstate.edu:td-1927 |
| Date | 07 August 2020 |
| Creators | Lucento, Marissa |
| Publisher | Scholars Junction |
| Source Sets | Mississippi State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
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