INRA, UMR1260 Lipid Nutrients and Prevention of Metabolic Diseases, F-13385 Marseille Cedex 5, France.
Prog Lipid Res. 2011 Oct;50(4):388-402. doi: 10.1016/j.plipres.2011.07.001. Epub 2011 Jul 8.
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.
在过去的十年中，我们对负责肠道水平脂溶性维生素摄取和转运的分子机制的理解有了相当大的进展。一方面，长期以来一直认为维生素 D、E 和β-胡萝卜素（人类饮食中主要的维生素 A 前体胡萝卜素）是通过被动扩散过程吸收的，尽管这不能解释这些分子吸收效率的广泛个体间变异性。另一方面，人们认为预先形成的维生素 A（视黄醇）和维生素 K1（叶绿醌）的吸收是通过能量依赖的过程发生的，但涉及的转运体尚未确定。最近发现能够促进肠细胞摄取和分泌维生素 E 和类胡萝卜素的肠道蛋白，这激发了人们对研究这些微量营养素吸收所涉及的基本机制的重新兴趣。迄今为止鉴定的蛋白包括胆固醇转运蛋白，如 SR-BI（清道夫受体 B 类 I）、CD36（簇分化抗原 36）、NPC1L1（尼曼-匹克 C1 样 1）或 ABCA1（ATP 结合盒 A1），它们具有广泛的底物特异性，但很可能还有其他膜蛋白也参与其中。在概述了人类上胃肠道腔中脂溶性维生素和类胡萝卜素的代谢之后，我们将重点介绍参与这些脂溶性维生素和类胡萝卜素肠内摄取、细胞内转运和基底外侧分泌的假定或已鉴定的蛋白，并概述未来需要探索的不确定性。鉴定参与肠细胞摄取和转运脂溶性维生素和类胡萝卜素的蛋白非常重要，特别是因为其中一些蛋白已经是开发能够减缓胆固醇吸收的药物的靶点。事实上，这些药物也可能干扰脂溶性维生素的摄取。更好地理解脂溶性维生素和类胡萝卜素吸收所涉及的分子机制是优化其生物利用度的优先事项。
