?-Carotene and its cleavage enzyme ?-carotene-15,15'-oxygenase (CMOI) affect retinoid metabolism in developing tissues.

ABSTRACT: The mammalian embryo relies on maternal circulating retinoids (vitamin A derivatives) for development. ?-Carotene is the major human dietary provitamin A. ?-Carotene-15,15'-oxygenase (CMOI) has been proposed as the main enzyme generating retinoid from ?-carotene in vivo. CMOI is expressed in embryonic tissues, suggesting that ?-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 ?-carotene was not present in any of the mouse diets, we unveiled a novel action of CMOI independent from its ?-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 ?-carotene can serve as an alternative vitamin A source for the in situ synthesis of retinoids in developing tissues by the action of CMOI.

SUBMITTER: Kim YK 

PROVIDER: S-EPMC3079298 | biostudies-other | 2011 May

REPOSITORIES: biostudies-other