title: β-Carotene and its cleavage enzyme β-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. β-Carotene is the major human dietary provitamin A. β-Carotene-15,15'-oxygenase (CMOI) has been proposed as the main enzyme generating retinoid from β-carotene in vivo. CMOI is expressed in embryonic tissues, suggesting that β-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 β-carotene was not present in any of the mouse diets, we unveiled a novel action of CMOI independent from its β-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 β-carotene can serve as an alternative vitamin A source for the in situ synthesis of retinoids in developing tissues by the action of CMOI.
authors.affiliation: Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901, USA.
authors.forename: Youn-Kyung
authors.initials: YK
authors.lastname: Kim
authors.forename: Lesley
authors.initials: L
authors.lastname: Wassef
authors.forename: Stacey
authors.initials: S
authors.lastname: Chung
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Jiang
authors.forename: Adrian
authors.initials: A
authors.lastname: Wyss
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
authors.forename: Loredana
authors.initials: L
authors.lastname: Quadro
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004622:Embryo, Mammalian / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D012176:Retinoids / Q000378:metabolism*; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics / Q000378:metabolism*
chemical_list: D012176:Retinoids; D012177:Retinol-Binding Proteins; D019207:beta Carotene; D014801:Vitamin A; D014212:Tretinoin; D050559:beta-Carotene 15,15'-Monooxygenase; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase