NAD-coupled enzymatic oxidation of O-ethyl O-p-nitrophenyl phenylphosphonothioate (EPN) to its oxygen analog with liver microsomes of rats.

S Sugiyama, T Igarashi, K Ueno, T Satoh, H Kitagawa

Index: Jpn. J. Pharmacol. 37(3) , 245-52, (1985)

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Abstract

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.