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.