Epithelial Transport and Function of Riboflavin

核黄素（RF）是一种水溶性维生素，对正常细胞功能和生长至关重要。在饮食剥夺或生理和病理应激期间，人类容易发生RF缺乏症。这导致各种临床异常，包括生长迟缓，贫血，皮肤病变和神经系统退行性变化。人类不能生物合成RF，因此必须通过小肠吸收从饮食中获得维生素。尽管许多研究都集中在射频吸收的机制上，但其确切的经上皮吸收机制仍存在争议，有待详细定义。射频吸收的细胞内过程，如细胞稳态，射频功能和调节也知之甚少。目前的建议旨在弥补我们对肠道射频吸收知识的这些空白。我们的长期目标是鉴定、分离、克隆和表征参与这种重要维生素上皮易位的蛋白质。我们的具体目标是：1)核黄素是通过受体介导和/或载体介导的途径转运到肠细胞的吗？2)射频是如何在细胞内运输的，它的储存空间的亚细胞定位是什么？3)可溶血浆RF结合蛋白是否参与RF易位？我们的多学科方法旨在提供射频传输的功能、细胞和分子水平的新的综合信息。这些研究将为复杂上皮运输机制提供新的重要信息，并为其结构特异性和功能提供重要的新见解。

Riboflavin (RF), a water-soluble vitamin, is essential for normal cellular functions and growth. During periods of dietary deprivation or physiological and pathological stress humans are vulnerable to developing RF deficiency. This results in a variety of clinical abnormalities, including growth retardation, anemia, skin lesions and degenerative changes in the nervous system. Humans cannot biosynthesize RF and, thus, must obtain the vitamin from the diet through absorption in the small intestine. Although many studies have focused on the mechanism of RF uptake, its definitive transepithelial absorption mechanism is controversial and remains to be defined in detail. Intracellular processes in RF absorption, such as cellular homeostasis, and RF function and regulation are also poorly understood. The current proposal aims to close these gaps in our knowledge of intestinal RF absorption. Our long-term objectives aim to identify, isolate, clone, and characterize the protein(s) involved in te epithelial translocation of this important vitamin. Our specific aims are: 1) Is riboflavin transported into enterocytes by a receptor- mediated and/or a carrier-mediated pathway? 2) How is RF trafficked within the cell and what is the subcellular localization of its storage compartment? 3) Is a soluble plasma RF-binding protein involved in RF translocation? Our multidisciplinary approach is designed to provide new and integrated information at the functional, cellular and molecular levels of RF transport. These studies will yield new and important information regarding a complex epithelial transport mechanism and provide important new insights in its structural specificity and function.