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Hydroxylation of acetone by ethanol‐ and acetone‐inducible cytochrome P‐450 in liver microsomes and reconstituted membranes
Author(s) -
Johansson Inger,
Eliasson Erik,
Norsten Carina,
Ingelman-Sundberg Magnus
Publication year - 1986
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(86)80214-9
Subject(s) - acetone , microsome , chemistry , hydroxylation , cytochrome , ethanol , membrane , cytochrome p450 , biochemistry , chromatography , metabolism , enzyme
Acetone oxidation in rat liver microsomes was induced 5‐ or 8‐fold by the treatment of the animals with ethanol or acetone, respectively. The apparent K m of the reaction was 0.9 mM, a value lower than the concentration reported for plasma acetone under starvation conditions. The major acetone metabolite was identified as acetol by GC‐MS. Acetone oxidation in microsomes was inhibited by typical P‐450 inhibitors as well as by compounds (e.g. imidazole) known to interact with the ethanol‐inducible P‐450 form. Antibodies against this P‐450 isozyme were inhibitory for the reaction in rabbit liver microsomes and this isozyme was the only one that showed acetone hydroxylation activity in reconstituted membranes. Imidazole inhibited the conversion of [ 14 C]acetone into low‐ M r compounds (e.g. glucose) in vivo. It is suggested that the ethanol‐and acetone‐inducible P‐450 make use of acetone as an endogenous substrate in the utilization of the compound for, e.g. glucose production under conditions of starvation and diabetic ketoacidosis.