Chrastil J, Wilson J T
J Pharmacol Exp Ther. 1975 May;193(2):631-8.
Time course studies of rho-nitroanisole O-demethylation revealed formaldehyde production in excess of rho-nitrophenol (PNP) and 4-nitrocatechol (NTC) formation by rat liver microsomes. This indicated that these products (PNP, NTC) were metabolised further. The hydroxylation reaction PNP yields NTC showed substrate and product inhibition and a requirement for reduced nicotinamide adenine dinucleotide phosphate and O2 and was localized in liver microsomes. It was strongly activated by ascorbic acid, cysteine, adenosine triphosphate or hydroxylamine in vitro and enhanced by phenobarbital treatment in vivo. Mercapturic derivatives were metabolized to the corresponding hydroxy compounds with the same speed as their parent compounds. Both PNP and NTC were metabolized to the corresponding glucuronide and sulfate conjugates. On the other hand, the PNP or NTC glucuronides and sulfates were metabolized with liver microsomes to PNP and NTC.
对ρ-硝基苯甲醚O-去甲基化的时程研究表明，大鼠肝微粒体产生的甲醛量超过了ρ-硝基苯酚（PNP）和4-硝基邻苯二酚（NTC）的生成量。这表明这些产物（PNP、NTC）会进一步代谢。PNP生成NTC的羟基化反应表现出底物和产物抑制作用，且需要还原型烟酰胺腺嘌呤二核苷酸磷酸和O2，该反应定位于肝微粒体中。在体外，它可被抗坏血酸、半胱氨酸、三磷酸腺苷或羟胺强烈激活，在体内可被苯巴比妥处理增强。硫醇尿酸衍生物代谢为相应羟基化合物的速度与其母体化合物相同。PNP和NTC均可代谢为相应的葡糖醛酸和硫酸盐结合物。另一方面，PNP或NTC的葡糖醛酸和硫酸盐与肝微粒体一起代谢为PNP和NTC。
