Nagao A.

National Food Research Institute, Tsukuba, Ibaraki 305-8642, Japan.

In vertebrates, provitamin A carotenoids are converted to retinal by beta-carotene-15,15'-dioxygenase. The enzyme activity is expressed specifically in intestinal epithelium and in liver. The intestinal enzyme not only plays an important role in providing animals with vitamin A, but also determines whether provitamin A carotenoids are converted to vitamin A or circulated in the body as intact carotenoids. We have found that a high fat diet enhanced the beta-carotene dioxygenase activity together with the cellular retinol binding protein type II level in rat intestines. Flavonols with a catechol structure in the B-ring and 2,6-di-tert-butyl-4-methylphenol inhibited the dioxygenase activity of pig intestinal homogenates and the conversion of beta-carotene to retinol in Caco-2 human intestinal cells. Thus, the bioavailability of dietary provitamin A carotenoids might be modulated by the other food components ingested. Regulation of the dioxygenase activity and its relation to the retinoid metabolism as well as to lipid metabolism deserve further study. In contrast to enzymatic cleavage, it is known that both retinal and beta-apocarotenals are formed in vitro from beta-carotene by chemical transformation, which cleaves conjugated double bonds at random positions under various oxidative conditions. Moreover, recent studies have indicated that the oxidation products formed by chemical transformation might have specific actions on the proliferation of certain cancer cells. We have found that lycopene, a typical nonprovitamin A carotenoid, was cleaved in vitro to acycloretinal, acycloretinoic acid and apolycopenals in a nonenzymatic manner, and that the mixture of oxidation products of lycopene induced apoptosis of HL-60 human promyelocytic leukemia cells. Thus, it is worth evaluating the formation of oxidation products and their biological actions, in order to elucidate the underlying mechanisms of the beneficial effects of carotenoids on human health.