PMID: 6981647Oct 10, 1982Paper

Kinetic evidence for heterogeneous responsiveness of mixed function oxidase isozymes to inhibition and induction by allylisopropylacetamide in chick embryo liver.

The Journal of Biological Chemistry
A B RifkindH Muschick

Abstract

Changes in hepatic mixed function oxidase kinetics after administration of allylisopropylacetamide (AIA) to chick embryos indicate that the activities of different cytochrome P-450 isozymes, including those participating in the metabolism of the same substrates, can be simultaneously increased and inhibited by a single xenobiotic. Up to 4 h after administration in ovo, or in vitro, AIA exclusively inhibited mixed function oxidases. At 24 h after administration in ovo, AIA simultaneously decreased the Vmax of the isozymes active in 7-ethoxycoumarin deethylation and in biphenyl and antipyrine hydroxylations in control liver and caused new isozymes with higher Km and Vmax values to appear. At the same time, AIA increased the Vmax values for isozymes active in aminopyrine demethylation and decreased the Vmax for benzo(a)pyrene hydroxylation (EC 1.14.14.1). As an inhibitor, AIA did not exhibit substrate selectivity but tended to inhibit isozymes with higher substrate affinity noncompetitively and lower affinity isozymes competitively. Competitive mechanisms and generalized P-450 breakdown could only partially account for the inhibition of mixed function oxidases by AIA. The inhibition at low doses of AIA (0.1 to 0.3 mg/egg) occurred...Continue Reading

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