Carotenes are one of the few food components for which there is strong evidence for an anti-carcinogenic role. However, the mechanism(s) by which carotenes work is uncertain. In part, this uncertainty is due to a lack in understanding of the normal metabolism of carotene. One possibility is that carotenoids such as beta-carotene are efficiently converted to retinoic acid, a molecule which has been shown to have profound cellular regulatory functions. The biochemical mechanism(s) whereby retinoic acid is produced will be determined. Using citral as a specific inhibitor of retinaldehyde oxidase, we will be able to examine the importance of central cleavage vs. excentric cleavage of beta-carotene for the generation of retinoic acid. There has been no suitable laboratory model in which to study carotene metabolism under controlled conditions. In this proposal, we will use the ferret as an in vivo model for human carotenoid metabolism. The ferret (like the human) absorbs a certain amount of intact beta- carotene and stores it in peripheral tissues. Homogenates of ferret, rat, and human tissue will be compared for their ability to metabolize beta- carotene to specific end products (e.g. retinoic acid). MOst beta-carotene conversion to retinoids takes place in the small intestine. In vivo experiments will be performed on ferrets using perfused gut segments to quantitate the absorption of intact beta-carotene and intestinally derived beta-apo-carotenoids and retinoids. recent observations that intestinal tissue significantly metabolizes beta-carotene to retinoic acid is of particular interest since this may be a partial explanation of carotene's anti-carcinogenic activity. The ferret model will enable future studies on the mechanisms involved in beta-carotene metabolism and factors which influence the metabolism of beta-carotene to beta-apo-carotenals and retinoic acid (e.g. vitamin E).
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