title: Vitamin A: overlapping delivery pathways to tissues from the circulation.
abstract: Although retinol bound to retinol-binding protein (RBP) is the most abundant retinoid form present in the circulations of humans and most mammals, other retinoid and proretinoid forms are also present in the blood. We are interested in understanding to what extent each of these circulating retinoid forms contributes towards retinoid actions within cells and tissues. Here we report two studies focused on this question. First, we examined retinoid transport and storage in RBP-deficient mice that lack circulating RBP. These mice under normal laboratory conditions are phenotypically normal except for a visual impairment early in life that is corrected if the mice are maintained on a vitamin A-sufficient diet throughout life. The RBP-deficient mice take up vitamin A from the diet into most tissues at least as well as wild type mice. Compared to wild type mice, mice lacking RBP accumulate excess vitamin A in the liver, since there is no RBP to facilitate mobilization of stored retinol from hepatic stores. In a second study, we explored in vitro the actions of carotene cleavage enzyme (CCE) in facilitating beta-carotene cleavage to retinoid in the testis. CCE is most highly expressed in the testis. Pull-down experiments coupled with MALDI-MS analysis showed that mouse testis CCE is able to interact with the testis-specific lactate dehydrogenase-C (LDH-C) isoform. This may suggest that CCE and LDH-C act in concert to catalyze beta-carotene cleavage.
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: Jisun
authors.initials: J
authors.lastname: Paik
authors.forename: Silke
authors.initials: S
authors.lastname: Vogel
authors.forename: Loredana
authors.initials: L
authors.lastname: Quadro
authors.forename: Roseann
authors.initials: R
authors.lastname: Piantedosi
authors.forename: Max
authors.initials: M
authors.lastname: Gottesman
authors.forename: Katherine
authors.initials: K
authors.lastname: Lai
authors.forename: Leora
authors.initials: L
authors.lastname: Hamberger
authors.forename: Milena de Morais
authors.initials: Mde M
authors.lastname: Vieira
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
mesh_terms: D000818:Animals; D001692:Biological Transport; D004032:Diet; D005982:Glutathione Transferase / Q000235:genetics; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D012177:Retinol-Binding Proteins / Q000172:deficiency / Q000378:metabolism; D013737:Testis / Q000201:enzymology; D014801:Vitamin A / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism; D050559:beta-Carotene 15,15'-Monooxygenase
chemical_list: D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D012177:Retinol-Binding Proteins; D019207:beta Carotene; D014801:Vitamin A; D007770:L-Lactate Dehydrogenase; D010105:Oxygenases; D050559:beta-Carotene 15,15'-Monooxygenase; D005982:Glutathione Transferase