PMID: 37321Jul 1, 1979

Metabolic conversion of fluorenone oxime to phenanthridinone by hepatic enzymes

Journal of Pharmaceutical Sciences
Y Golander, L Sternson

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.

References

Aug 15, 1977·Experientia·L Sternson, F Hincal

Citations

Nov 7, 1986·Biochimica Et Biophysica Acta·J B MangoldA Spina
Mar 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Satoko SugawaraHiroyuki Kasahara

Related Concepts

Metabolic Biotransformation
Fluorenes
Hydrogen-Ion Concentration
Liver
Ketoximes
Phenanthridines

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