Nadh synergism of microsomal aniline metabolism in the presence of enhancing agents

Stimulation of the mouse hepatic microsomal aniline p-hydroxylases by acetone and polyamines

“…Consistant with previous reports (Anders, 1968(Anders, , 1969(Anders, , 1972Anders and Gander, 1979;Vianio and Hanninen, 1972;Powis et al, 1977;Bidlack and Lowery, 1982) acetone alone was found to stimulate TAH ( Fig. 1).…”

“…Similarly, Anders and Gander (1979) reported a marked dependence of acetone enhancement on aniline concentration and the stimulation, in general, was greater in NADPH/oxygen as well as cumene hydroperoxide supported reactions when lower aniline concentrations were used. Although in all the previous investigations (Anders, 1968(Anders, , 1969(Anders, , 1972Anders and Gander, 1979;Vianio and Hanninen, 1972;Powis et al, 1977;Bidlack and Lowery, 1982), only the stimulatory effect of acetone had been the focal point of proposed mechanisms, our data (Figs 1-3) indicate that at higher acetone concentrations, the activity-response curves for TAH, AH-I as well as AH-II do not plateau but rather exhibit a gradual decline in stimulation. This was also noted by Anders (1968) with rat liver microsomes and by Kitada et al (1983) in the reconstituted systems.…”

“…It is currently believed that acetone enhancement of aniline p-hydroxylation probably involves either facilitated introduction of second electron (Powis et al, 1977), a site for formation or insertion of activated oxygen into the substrate (Anders and Gander, 1979) and/or multiple forms of aniline p-hydroxylase Fig. 3.…”

Inhibition of p-Aminophenol Metabolism: a Possible Mechanism of Enhancement of Aniline Hydroxylation

“…Moreover, Prowis and Boobis (30) feel that enhancement involves interaction with a type I binding site. They postulated that enhancement occurs through facilitation of transfer of the second electron to the enzyme-substrate com plex ( 10). Furthermore, they reported that PAP formation from aniline was unaffected by cyanide, which would be anticipated to increase the recovery effect of PAP through inhibition of its metabolism by cyanide-sensitive factor.…”

“…For example, the combination of acetone and ethyl isocyanide enhanced aniline metabolism above the maximum level produced by acetone alone. Proposed mechanisms for enhancement in clude: (a) an increased rate of reduction of cytochrome P-450 in the presence of ethyl isocyanide (2); (b) uncompetitive activation of aniline hydroxylase by acetone (1); (c) inter action of metyrapone with substrate binding sites (9), and (d) facilitation of transfer of the second electron to the cytochrome P-450 sub strate complex (10).…”