Kinetics, activation, and induction of aortic mono-oxygenases-biotransformation of benzo[a]pyrene

James A. Bond, Curtis J. Omiecinski, Mont R. Juchau

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Aortic aryl hydrocarbon hydroxylase (EC, a cytochrome P-450-dependent mono-oxygenase complex potentially important in the etiology of atherosclerosis, was detected previously in aortic homogenates of humans, monkeys and rabbits [M. R. Juchau, J. A. Bond and E. P. Benditt, Proc. natn. Acad. Sci. U.S.A. 73, 3723 (1976)]. The present study more fully characterizes the mono-oxygenase activity in aortas of treated and untreated New Zealand White rabbits. A 2-fold activation was obtained with NADH (7 × 10-4 M) at saturating concentrations of NADPH. Addition of heme (9 μm) increased the enzymatic activity 2- to 4-fold during a 15-min incubation and over 25-fold during a 2-hr incubation. The results suggest the presence of relatively high concentrations of apoprotein in the aortic tissues. Kinetic studies in the presence of heme yielded an apparent Km of 1 × 10-4 M and Vmax of 15.24 pmoles/mg of protein/min with respect to NADPH. A sigmoidal curve was obtained with varying benzo[a]pyrene concentrations (0.5 to 80 μM), suggesting the possibility of allosterism. Aroclor 1254,3-methylcholanthrene and 5,6-benzoflavone acted to induce the cytochrome P-450-dependent mono-oxygenase, while pheno-barbital and pregnenolone 16α-carbonitrile demonstrated little, if any, induction capacity. Analyses of metabolites formed in induced aortas with high-pressure liquid chromatography revealed the formation (in each case) of primarily the phenolic metabolites of benzo[a]pyrene.

Original languageEnglish (US)
Pages (from-to)305-311
Number of pages7
JournalBiochemical Pharmacology
Issue number2
StatePublished - 1979

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology


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