Epithelial Transport and Function of Riboflavin

核黄素(RF)是一种水溶性维生素，对细胞的正常功能和生长是必不可少的。在饮食剥夺或生理和病理压力期间，人类容易患上射频缺乏症。这会导致各种临床异常，包括生长迟缓、贫血、皮肤损害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。虽然许多研究都集中在射频吸收的机制上，但其确切的跨上皮吸收机制仍存在争议，仍有待详细定义。对RF吸收的细胞内过程，如细胞内稳态，以及RF的功能和调节也知之甚少。目前的建议旨在填补我们对肠道射频吸收知识的这些空白。我们的长期目标是识别、分离、克隆和鉴定与这种重要维生素的TE上皮转位有关的蛋白质(S)。我们的具体目标是：1)核黄素是通过受体和/或载体介导的途径转运到肠细胞中的？2)RF是如何在细胞内运输的？其储存室的亚细胞定位是什么？3)可溶性血浆RF结合蛋白是否参与了RF的转运？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和集成的信息。这些研究将产生关于复杂的上皮运输机制的新的和重要的信息，并对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.