The formation, occurrence, and function of β-apocarotenoids: β-carotene metabolites that may modulate nuclear receptor signaling

beta-Carotene is the major dietary source of provitamin A. Central cleavage of beta-carotene yields 2 molecules of retinal followed by further oxidation to retinoic acid. Eccentric cleavage of beta-carotene occurs at double bonds other than the central double bond, and the products of these reactions are beta-apocarotenals and beta-apocarotenones. We reviewed recent developments in 3 areas: 1): the enzymatic production of beta-apocarotenoids in higher animals; 2) the occurrence of beta-apocarotenoids in foods and animal tissues; and 3) the biological activity of b-apocarotenoids, particularly on retinoid receptors. HPLC-mass spectrometry techniques were developed to quantify these compounds in mouse serum and tissues and in foods. beta-Apo-10'- and -12'- carotenals were detected in mouse serum and liver. beta-Apo-8'-, beta-apo-10'-, beta-apo-12'-, and beta-apo-14'- carotenals and beta-apo-13-carotenone were detected in orange-fleshed melons. Transactivation assays were performed to see whether apocarotenoids activate or antagonize retinoid X receptor (RXR) alpha. Reporter gene constructs and retinoid receptor (RXR alpha) were transfected into cells, which were used to perform quantitative assays for the activation of this ligand-dependent transcription factor. None of the beta-apocarotenoids significantly activated RXR alpha. However, beta-apo-13-carotenone antagonized the 9-cis-retinoic acid activation of RXR alpha. Competitive radioligand binding assays showed that this antagonist competes directly with the agonist for binding to purified receptor, a finding confirmed by molecular modeling studies. These findings suggest that a possible biological function of beta-apocarotenoids is their ability to interfere with nuclear receptor signaling. Recent work showed that beta-apo-13-carotenone is also a high-affinity antagonist of all 3 retinoic acid receptors (RAR alpha, RAR beta, and RAR gamma). Am J Clin Nutr 2012;96(suppl):1189S-92S.