IN-VITRO AND IN-VIVO INHIBITION OF BETA-CAROTENE DIOXYGENASE ACTIVITYBY CANTHAXANTHIN IN RAT INTESTINE

beta-Carotene dioxygenase catalyzes the conversion of provitamin A car otenoids to vitamin A in mammalian tissues. Whether the enzyme can als o cleave non-provitamin A carotenoids to retinoid analogs with biologi cal activities is still unclear. We investigated (i) substrate specifi cities of beta-carotene dioxygenase toward provitamin A and non-provit amin A carotenoids and (ii) potential antagonistic effects of non-prov itamin A carotenoids on beta-carotene conversion to vitamin A. Provita min A substrates were 8 to 23% as active as beta-carotene. No polar me tabolites were detected with canthaxanthin or zeaxanthin as substrates ; these compounds efficiently inhibited the beta-carotene cleavage rea ction by 71 and 40%, respectively. Kinetic studies indicated mixed inh ibition for canthaxanthin (K-i = 1.6 mu M) and non-competitive for zea xanthin (K-i = 7.8 mu M), suggesting that both compounds do not intera ct significantly with the active site of the enzyme. In vivo, dietary combinations of canthaxanthin and beta-carotene resulted in lower live r levels of both carotenoids and vitamin A and in a higher beta-carote ne/vitamin A ratio as compared to groups supplemented with the compoun ds 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 altho ugh canthaxanthin is not a substrate for beta-carotene dioxygenase, it is likely to affect the activity of provitamin A carotenoids by direc t interaction with the enzyme. (C) 1997 Academic Press.