Grolier P, Duszka C, Borel P, Alexandre-Gouabau M C, Azais-Braesco V
Unité des Maladies Métaboliques et Micronutriments, CRNH-INRA, Clermont-Ferrand, France.
Arch Biochem Biophys. 1997 Dec 15;348(2):233-8. doi: 10.1006/abbi.1997.0388.
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.
β-胡萝卜素双加氧酶催化哺乳动物组织中维生素A原类胡萝卜素向维生素A的转化。该酶是否还能将非维生素A原类胡萝卜素裂解为具有生物活性的类视黄醇类似物仍不清楚。我们研究了：（i）β-胡萝卜素双加氧酶对维生素A原和非维生素A原类胡萝卜素的底物特异性；（ii）非维生素A原类胡萝卜素对β-胡萝卜素转化为维生素A的潜在拮抗作用。维生素A原底物的活性是β-胡萝卜素的8%至23%。以角黄素或玉米黄质为底物时未检测到极性代谢物；这些化合物分别有效抑制β-胡萝卜素裂解反应71%和40%。动力学研究表明，角黄素为混合抑制（Ki = 1.6 microM），玉米黄质为非竞争性抑制（Ki = 7.8 microM），这表明这两种化合物均未与该酶的活性位点发生显著相互作用。在体内，与分别补充这些化合物的组相比，角黄素和β-胡萝卜素的饮食组合导致肝脏中这两种类胡萝卜素和维生素A的水平降低，且β-胡萝卜素/维生素A比值升高。这支持了高剂量角黄素与β-胡萝卜素竞争肠道吸收并抑制β-胡萝卜素转化为维生素A的观点。因此，我们认为，尽管角黄素不是β-胡萝卜素双加氧酶的底物，但它可能通过与该酶直接相互作用来影响维生素A原类胡萝卜素的活性。
