β-Carotene and its cleavage enzyme β-carotene-15,15′-oxygenase (CMOI) affect retinoid metabolism in developing tissues

The mammalian embryo relies on maternal circulating retinoids (vitamin A derivatives) for development. beta-Carotene is the major human dietary provitamin A. beta-Carotene-15,15'-oxygenase (CMOI) has been proposed as the main enzyme generating retinoid from beta-carotene in vivo. CMOI is expressed in embryonic tissues, suggesting that beta-carotene provides retinoids locally during development. We performed loss of CMOI function studies in mice lacking retinol-binding protein (RBP), an established model of embryonic vitamin A deficiency (VAD). We show that, unexpectedly, lack of CMOI in the developing tissues further exacerbates the severity of VAD and thus the embryonic malformations of RBP(-/-) mice. Since beta-carotene was not present in any of the mouse diets, we unveiled a novel action of CMOI independent from its beta-carotene cleavage activity. We also show for the first time that CMOI exerts an additional function on retinoid metabolism by influencing retinyl ester formation via modulation of lecithin: retinol acyltransferase (LRAT) activity, at least in developing tissues. Finally, we demonstrate unequivocally that beta-carotene can serve as an alternative vitamin A source for the in situ synthesis of retinoids in developing tissues by the action of CMOI.-Kim, Y.-K., Wassef, L., Chung, S., Jiang, H., Wyss, A., Blaner, W. S., Quadro, L. beta-Carotene and its cleavage enzyme beta-carotene-15,15'-oxygenase (CMOI) affect retinoid metabolism in developing tissues. FASEB J. 25, 1641-1652 (2011). www.fasebj.org