Inhibitory Effects of Vitamin A and Vitamin K on Rat Cytochrome P4501A1-Dependent Monooxygenase Activity

doi:10.1006/bbrc.1999.1240

Biochemical and Biophysical Research Communications

Volume 262, Issue 2, 27 August 1999, Pages 565-569

https://doi.org/10.1006/bbrc.1999.1240 Get rights and content

Abstract

The inhibitory effects of vitamins A and K toward P4501A1-dependent 7-ethoxycoumarin O-deethylation were examined in the reconstituted system containing the microsomal fraction prepared from the recombinant Saccharomyces cerevisiae cells producing rat P4501A1 and yeast NADPH-P450 reductase. On vitamins A, all-trans-retinol, all-trans-retinal, all-trans-retinoic acid and retinol-palmitate showed competitive inhibition with K_i values of 0.068, 0.079, 2.6 and 2.0 μM, respectively. Judging from the K_i values, the inhibitory effects of those vitamins A appear to have physiological significance on the basis of their contents in liver, lung and kidney. On vitamins K, vitamin K₁ showed competitive inhibition with K_i value of 24 μM, while vitamin K₂ showed noncompetitive inhibition with K_i value of 60 μM. Judging from these K_i values together with the contents of these vitamins K in liver, the inhibitory effects of the vitamins K are not as significant as those of vitamins A. These results suggest that the ingestion of enough amounts of vitamins A from foods might lead to the inhibition of the activity of P4501A1 which is known to be induced by smoking, drugs such as omeprazole and lansoprazole, and environmental pollutants like dioxins.

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^☆: Abbreviation used: P450, cytochrome P450

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Regular ArticleInhibitory Effects of Vitamin A and Vitamin K on Rat Cytochrome P4501A1-Dependent Monooxygenase Activity☆

Abstract

J. Am. Chem. Soc.

Biochim. Biophys. Acta

Proc. Natl. Acad. Sci. USA

J. Natl. Cancer Inst.

J. Biochem.

Acta Biol. Med. Ger.

Eur. J. Biochem.

Biochem. Biophys. Res. Commun.

Arch. Biochem. Biophys.

Biochemistry

J. Biochem.

DNA Cell Biol.

DNA

Biochem. Biophys. Res. Commun.

J. Biochem.

Regular Article
Inhibitory Effects of Vitamin A and Vitamin K on Rat Cytochrome P4501A1-Dependent Monooxygenase Activity☆