Proteins involved in uptake, intracellular transport and basolateral secretion of fat-soluble vitamins and carotenoids by mammalian enterocytes |
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Authors: | Emmanuelle Reboul Patrick Borel |
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Affiliation: | INRA, UMR1260 “Lipid Nutrients and Prevention of Metabolic Diseases”, F-13385 Marseille Cedex 5, France;INSERM, U1025 “Bioavailability of Micronutrients”, F-13385 Marseille Cedex 5, France;Univ Aix-Marseille, F-13385 Marseille Cedex 5, France |
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Abstract: | Our understanding of the molecular mechanisms responsible for fat-soluble vitamin uptake and transport at the intestinal level has advanced considerably over the past decade. On one hand, it has long been considered that vitamin D and E as well as β-carotene (the main provitamin A carotenoid in human diet) were absorbed by a passive diffusion process, although this could not explain the broad inter-individual variability in the absorption efficiency of these molecules. On the other hand, it was assumed that preformed vitamin A (retinol) and vitamin K1 (phylloquinone) absorption occurred via energy-dependent processes, but the transporters involved have not yet been identified. The recent discovery of intestinal proteins able to facilitate vitamin E and carotenoid uptake and secretion by the enterocyte has spurred renewed interest in studying the fundamental mechanisms involved in the absorption of these micronutrients. The proteins identified so far are cholesterol transporters such as SR-BI (scavenger receptor class B type I), CD36 (cluster determinant 36), NPC1L1 (Niemann–Pick C1-like 1) or ABCA1 (ATP-Binding Cassette A1) displaying a broad substrate specificity, but it is likely that other membrane proteins are also involved. After overviewing the metabolism of fat-soluble vitamins and carotenoids in the human upper gastrointestinal lumen, we will focus on the putative or identified proteins participating in the intestinal uptake, intracellular transport and basolateral secretion of these fat-soluble vitamins and carotenoids, and outline the uncertainties that need to be explored in the future. Identifying the proteins involved in intestinal uptake and transport of fat-soluble vitamins and carotenoids across the enterocyte is of great importance, especially as some of them are already targets for the development of drugs able to slow cholesterol absorption. Indeed, these drugs may also interfere with lipid vitamin uptake. A better understanding of the molecular mechanisms involved in fat-soluble vitamin and carotenoid absorption is a priority to better optimize their bioavailability. |
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Keywords: | Abbreviations: ABCA1, ATP Binding Cassette A1 ABCG1, ATP Binding Cassette G1 ABCG5, ATP Binding Cassette G5 ABCG8, ATP Binding Cassette G8 BBM, brush border membrane CBP, carotenoid-binding protein CD36, cluster determinant 36 CDBP, cytosol vitamin D-binding protein CRBPII, cellular retinol binding protein II FSV& C, fat soluble vitamins and carotenoids GI, gastrointestinal GSTP1, Glutathione S-Transferase Pi 1 HR-LBP, Human Retinal Lutein-Binding Protein IDBP, intracellular vitamin D binding protein Isx, Intestine Specific Homebox L-FABP, Liver Fatty-Acid-Binding Protein LRAT, Lecithin Retinol Acyl Transferase NPC1L1, Niemann&ndash Pick C1-like 1 RBP, retinol binding protein SR-BI, scavenger receptor class B type 1 STRA6, STimulated by Retinoic Acid 6 TAP, tocopherol-associated protein α-TTP, α-tocopherol transfer protein |
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