In vitro and in vivo inhibition of beta-carotene dioxygenase activity by canthaxanthin in rat intestine.
beta-Carotene dioxygenase catalyzes the conversion of provitamin A carotenoids to vitamin A in mammalian tissues. Whether the enzyme can also cleave non-provitamin A carotenoids to retinoid analogs with biological activities is still unclear. We investigated (i) substrate specificities of beta-carotene dioxygenase toward provitamin A and non-provitamin A carotenoids and (ii) potential antagonistic effects of non-provitamin A carotenoids on beta-carotene conversion to vitamin A. Provitamin A substrates were 8 to 23% as active as beta-carotene. No polar metabolites were detected with canthaxanthin or zeaxanthin as substrates; these compounds efficiently inhibited the beta-carotene cleavage reaction by 71 and 40%, respectively. Kinetic studies indicated mixed inhibition for canthaxanthin (Ki = 1.6 microM) and non-competitive for zeaxanthin (Ki = 7.8 microM), suggesting that both compounds do not interact significantly with the active site of the enzyme. In vivo, dietary combinations of canthaxanthin and beta-carotene resulted in lower liver levels of both carotenoids and vitamin A and in a higher beta-carotene/vitamin A ratio as compared to groups supplemented with the compounds separately. This supports the view that canthaxanthin at high doses competes with beta-carotene for intestinal absorption and inhibits the conversion of beta-carotene to vitamin A. Thus, we suggest that although canthaxanthin is not a substrate for beta-carotene dioxygenase, it is likely to affect the activity of provitamin A carotenoids by direct interaction with the enzyme.
Grolier
P
P
Unité des Maladies Métaboliques et Micronutriments, CRNH-INRA, Clermont-Ferrand, France.
Duszka
C
C
Borel
P
P
Alexandre-Gouabau
M C
MC
Azais-Braesco
V
V
D000818:Animals; D001665:Binding Sites; D016644:Canthaxanthin / Q000494:pharmacology*; D002338:Carotenoids / Q000378:metabolism; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000201:enzymology*; D007700:Kinetics; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D009929:Organ Size; D010105:Oxygenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity; D014801:Vitamin A / Q000378:metabolism; D024341:Xanthophylls; D065146:Zeaxanthins; D019207:beta Carotene / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D050559:beta-Carotene 15,15'-Monooxygenase
C493357:Bco1 protein, rat; D004791:Enzyme Inhibitors; D024341:Xanthophylls; D065146:Zeaxanthins; D019207:beta Carotene; D014801:Vitamin A; D002338:Carotenoids; D016644:Canthaxanthin; D010105:Oxygenases; D050559:beta-Carotene 15,15'-Monooxygenase