NAD-coupled enzymatic oxidation of O-ethyl O-p-nitrophenyl phenylphosphonothioate (EPN) to its oxygen analog with liver microsomes of rats.
O-Ethyl O-p-nitrophenyl phenylphosphonothioate (EPN)-induced inhibition of rat liver microsomal carboxylesterase (CEase) and formation of O-ethyl O-p-nitrophenyl phenylphosphonate (EPNoxon), an oxygen analog of EPN, were enhanced remarkably by addition of NAD in vitro. This potentiation of the anti-CEase action of EPN by NAD was significantly inhibited by addition of SKF 525-A or potassium thiocyanate (KSCN); and a simultaneous decrease in cytochrome P-450 contents were also observed. Addition of N-ethylmaleimide (NEM) at various concentrations inhibited potentiation of the anti-CEase action of EPN by NAD in parallel with inhibition of liver microsomal dehydrogenase activities. In conclusion, NAD was enzymatically reduced to NADH, a cofactor of microsomal dehydrogenase(s), and then formation of EPNoxon through microsomal cytochrome P-450-coupled monooxygenase was accelerated. Consequently, inhibition of CEase by EPN was potentiated.
D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002802:Cholinesterases / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004221:Disulfiram / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005233:Fatty Alcohols / Q000494:pharmacology; D066298:In Vitro Techniques; D007306:Insecticides / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D004849:Phenylphosphonothioic Acid, 2-Ethyl 2-(4-Nitrophenyl) Ester / Q000031:analogs & derivatives / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D005233:Fatty Alcohols; D007306:Insecticides; D009243:NAD; C032085:EPN oxon; D004849:Phenylphosphonothioic Acid, 2-Ethyl 2-(4-Nitrophenyl) Ester; D003577:Cytochrome P-450 Enzyme System; C005031:cetyl alcohol; D006899:Mixed Function Oxygenases; D000444:Aldehyde Dehydrogenase; D002265:Carboxylic Ester Hydrolases; D002802:Cholinesterases; D005033:Ethylmaleimide; D004221:Disulfiram