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，人类容易发展RF缺乏。 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的退行性变化。 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。 虽然许多研究都集中在RF摄取的机制，其明确的跨上皮吸收机制是有争议的，仍有待详细定义。RF吸收的细胞内过程，如细胞内稳态，以及RF功能和调节也知之甚少。 目前的建议旨在填补我们对肠道RF吸收知识的这些空白。我们的长期目标是鉴定，分离，克隆和表征这种重要维生素的上皮易位所涉及的蛋白质。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上皮细胞中的吗？2)RF如何在细胞内运输，其储存室的亚细胞定位是什么？3)可溶性血浆RF结合蛋白是否参与RF易位？我们的多学科方法旨在提供新的和综合的信息在功能，细胞和分子水平的射频传输。 这些研究将产生新的和重要的信息，关于一个复杂的上皮运输机制，并提供重要的新见解，其结构特异性和功能。

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.