Inhibitory effects of vitamin A and vitamin K on rat cytochrome P4501A1-dependent monooxygenase activity.
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 microM, 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 K(1) showed competitive inhibition with K(i) value of 24 microM, while vitamin K(2) showed noncompetitive inhibition with K(i) value of 60 microM. 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.
Inouye
K
K
Graduate School of Agriculture, Kyoto University, Kitashirakawa, Oiwake-cho, Sakyo-ku, Kyoto, 606-8502, Japan. inouye@kais.kyoto-u.ac.jp
Mae
T
T
Kondo
S
S
Ohkawa
H
H
D000818:Animals; D003374:Coumarins / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D004224:Diterpenes; D007700:Kinetics; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D009249:NADP / Q000378:metabolism; D010105:Oxygenases / Q000037:antagonists & inhibitors* / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D000084562:Retinyl Esters; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000031:analogs & derivatives / Q000494:pharmacology*; D014812:Vitamin K / Q000494:pharmacology*
D003374:Coumarins; D004224:Diterpenes; D011994:Recombinant Proteins; D000084562:Retinyl Esters; D014801:Vitamin A; D014812:Vitamin K; C014794:retinol palmitate; C017299:7-ethoxycoumarin; D009249:NADP; D014212:Tretinoin; D010105:Oxygenases; D019363:Cytochrome P-450 CYP1A1