Inhibitory effects of vitamin A and vitamin K on rat cytochrome P4501Al-dependent monooxygenase activity

The inhibitory effects of vitamins A and K toward P4501A1-dependent 7-ethox ycoumarin O-deethylation were examined in the reconstituted system containi ng the microsomal fraction prepared from the recombinant Saccharomyces cere visiae cells producing rat P4501A1 and yeast NADPH-P450 reductase. On vitam ins A, all-trans-retinol, all-trans-retinal, all-trans-retinoic acid and re tinol-palmitate showed competitive inhibition with K-i values of 0.068, 0.0 79, 2.6 and 2.0 mu M, respectively. Judging from the K-i values, the inhibi tory effects of those vitamins A appear to have physiological significance on the basis of their contents in liver, lung and kidney. On vitamins K, vi tamin K-1 showed competitive inhibition with K-i value of 24 mu M, while vi tamin K-2 showed noncompetitive inhibition with K-i value of 60 mu M. Judgi ng 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 t hose of vitamins A. These results suggest that the ingestion of enough amou nts of vitamins A from foods might lead to the inhibition of the activity o f P4501A1 which is known to be induced by smoking, drugs such as omeprazole and lansoprazole, and environmental pollutants like dioxins. (C) 1999 Acad emic Press.