title: Metabolic conversion of fluorenone oxime to phenanthridinone by hepatic enzymes.
abstract: Fluorenone oxime is converted to phenanthridinone by enzymes present in rat liver homogenates. The reaction is analogous to the chemical Beckman rearrangement. The oxime-amide rearrangement enzyme is localized primarily in the microsomes, with some activity in the cytosol. The reaction requires reduced nicotinamide adenine dinucleotide phosphate and observes Michaelis-Menten kinetics. The reaction is relatively slow (Vmax = 7.75 +/- 2.01 nmoles of phenanthridinone formed/100 mg of liver/15 min), but the enzyme reaches maximum velocity at relatively low substrate concentrations (Km = 3.90 +/- 1.85 x 10(-5) M). The reaction is strongly competitively inhibited by 1-decylimidazole (KI = 3.75 +/- 1.77 X 10(-7) M) and inhibited to a lesser extent by the chelating agents bipyridyl (KI = 1.33 +/- 0.21 X 10(-3) M) and ethylenediamine tetraacetate (KI = 1.00 +/- 0.28 X 10(-3) M) and the sulfhydryl binding agent p-chloromercuribenzoate (KI = 2.71 +/- 0.07 X 10(-4) M). Studies also suggest that the reaction mechanism does not involve initial enzymatic substrate esterification through acetylation, glucuronidation, phosphorylation, or sulfation.
mesh_terms: D000818:Animals; D001711:Biotransformation; D005449:Fluorenes / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D010091:Oximes / Q000378:metabolism*; D010617:Phenanthridines / Q000378:metabolism*; D051381:Rats
chemical_list: D005449:Fluorenes; D010091:Oximes; D010617:Phenanthridines