Open AccessNAD-Coupled Enzymatic Oxidation of O-Ethyl O-p-Nitrophenyl Phenylphosphonothioate (EPN) to Its Oxygen Analog with Liver Microsomes of Rats
Author(s) -
S Sugiyama,
Takashi Isobe,
Koichi Ueno,
Tetsuo Satoh,
Haruo Kitagawa
Publication year - 1985
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.37.245
Subject(s) - nad+ kinase , chemistry , microsome , cytochrome , cofactor , carboxylesterase , enzyme , biochemistry , monooxygenase , cytochrome p450
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.