Dark side to beta-carotene; implications for golden rice
The scientists who did this study say it may have implications for golden rice: "A concern is that if you engineer these crops to have unusually high levels of beta-carotene, they might also have high levels of these [Vitamin A-blocking] compounds."
For our backgrounder on golden rice see:
Naturally Occurring Eccentric Cleavage Products of Provitamin A Î²-Carotene Function as Antagonists of Retinoic Acid Receptors
Abdulkerim Eroglu, Damian P. Hruszkewycz, Carlo dela Sena, Sureshbabu Narayanasamy, Ken M. Ried, Rachel E. Kopec”–, Steven J. Schwart, Robert W. Curley Jr. and Earl H. Harrison
The Journal of Biological Chemistry
© 2012 by The American Society for Biochemistry and Molecular Biology
Î²-Carotene is the major dietary source of provitamin A. Central cleavage of Î²-carotene catalyzed by Î²-carotene oxygenase 1 yields two molecules of retinaldehyde. Subsequent oxidation produces all-trans-retinoic acid (ATRA), which functions as a ligand for a family of nuclear transcription factors, the retinoic acid receptors (RARs). Eccentric cleavage of Î²-carotene at non-central double bonds is catalyzed by other enzymes and can also occur non-enzymatically. The products of these reactions are Î²-apocarotenals and Î²-apocarotenones, whose biological functions in mammals are unknown. We used reporter gene assays to show that none of the Î²-apocarotenoids significantly activated RARs. Importantly, however, Î²-apo-14”²-carotenal, Î²-apo-14”²-carotenoic acid, and Î²-apo-13-carotenone antagonized ATRA-induced transactivation of RARs. Competitive radioligand binding assays demonstrated that these putative RAR antagonists compete directly with retinoic acid for high affinity
to purified receptors. Molecular modeling studies confirmed that Î²-apo-13-carotenone can interact directly with the ligand binding site of the retinoid receptors. Î²-Apo-13-carotenone and the Î²-apo-14”²-carotenoids inhibited ATRA-induced expression of retinoid responsive genes in Hep G2 cells. Finally, we developed an LC/MS method and found 3 5 nM Î²-apo-13-carotenone was present in human plasma. These findings suggest that Î²-apocarotenoids function as naturally occurring retinoid antagonists. The antagonism of retinoid signaling by these metabolites may have implications for the activities of dietary Î²-carotene as a provitamin A and as a modulator of risk for cardiovascular disease and cancer.