Carotenoids, beta-Apocarotenoids, and Retinoids: The Long and the Short of It

Naturally occurring retinoids (retinol, retinal, retinoic acid, retinyl esters) are a subclass of beta-apocarotenoids, defined by the length of the polyene side chain. Provitamin A carotenoids are metabolically converted to retinal (beta-apo-15-carotenal) by the enzyme beta-carotene-15,15'-dioxygenase (BCO1) that catalyzes the oxidative cleavage of the central C=C double bond. A second enzyme beta-carotene-9'-10'-dioxygenase cleaves the 9',10' bond to yield beta-apo-10'-carotenal and beta-ionone. Chemical oxidation of the other double bonds leads to the generation of other beta-apocarotenals. Like retinal, some of these beta-apocarotenals are metabolically oxidized to the corresponding beta-apocarotenoic acids or reduced to the beta-apocarotenols, which in turn are esterified to beta-apocarotenyl esters. Other metabolic fates such as 5,6-epoxidation also occur as for retinoids. Whether the same enzymes are involved remains to be understood. beta-Apocarotenoids occur naturally in plant-derived foods and, therefore, are present in the diet of animals and humans. However, the levels of apocarotenoids are relatively low, compared with those of the parent carotenoids. Moreover, human studies show that there is little intestinal absorption of intact beta-apocarotenoids. It is possible that they are generated in vivo under conditions of oxidative stress. The beta-apocarotenoids are structural analogs of the naturally occurring retinoids. As such, they may modulate retinoid metabolism and signaling. In deed, those closest in size to the C-20 retinoids-namely, beta-apo-14'-carotenoids (C-22) and beta-apo-13-carotenone (C-18) bind with high affinity to purified retinoid receptors and function as retinoic acid antagonists in transactivation assays and in retinoic acid induction of target genes. The possible pathophysiologic relevance in human health remains to be determined.