CHEMISTRY AND METABOLISM OF A MAMMALIAN SIDEROPHOR

铁是生物圈中最丰富的金属之一， 对大多数生物系统的营养。 由于其特征Fe（II）， Fe（III）的氧化还原电位铁参与了广泛的关键 生化反应。 即使不是所有的生物体， 铁结合，运输和储存分子，以维持铁 体内平衡 微生物产生低分子量铁载体， 结合铁并促进有机体的生长。 在高等动物中，铁 运输和储存蛋白如转铁蛋白和铁蛋白已经被 很好的描述。 然而，中间体没有得到很好的表征， 转铁蛋白、铁蛋白和铁的其它位点之间的铁转运系统 证词 可实现该功能的低分子量配体 在高等动物中已经被假设，但尚未确定。 我们有 鉴定并纯化了约1500分子量的肽 其显示铁载体活性。 这种化合物， 转移因子（HAITF）是从哺乳动物组织中分离出来的， 显示通过铁转运促进革兰氏阴性细菌生长 机制 该提案概述了一项计划， 这种化合物的化学性质和代谢意义 研究是 用来确定一级结构光谱参数 与铁结合相关，并阐明铁结合配体 分子。 代谢研究旨在评估任何可能的作用 在细胞内铁转运中。 最后，将继续对HAITF进行研究 在疾病状态下，与异常铁稳态有关。 这个项目 将不仅评估这种化合物作为铁运输的重要性， 机制，但应提供新的见解，铁的调节 与异常铁稳态相关的代谢和机制。

Iron, one of the most abundant metals in the biosphere, is a critical nutrient to most biological systems. Due to its characteristic Fe(II) to Fe(III) redox potential iron participates in a wide range of crucial biochemical reactions. Most, if not all organisms have evolved complex iron binding, transport, and storage molecules to maintain iron homeostasis. Microbes manufacture low molecular weight siderophores which bind iron and promote the growth of the organism. In higher animals, iron transport and storage proteins such as transferrin and ferritin have been well characterized. Not well characterized, however, is the intermediate iron transport system between transferrin, ferritin and other sites of iron deposition. Low molecular weight ligands which may fulfill this function in higher animals have been hypothesized but not identified. We have identified and purified a peptide of approximately 1500 molecular weight which displays siderophore activity. This compound, Host Associated Iron Transfer Factor (HAITF), was isolated from mammalian tissue and has been shown to promote growth of gram negative bacteria by an iron transport mechanism. This proposal outlines a plan for further characterizing the chemical nature and metabolic significance of this compound. Studies are designed to determine the primary structure, spectroscopic parameters associated with iron binding and to elucidate the iron binding ligands on the molecule. Metabolic studies are designed to assess any possible role in intracellular iron transport. Finally, studies of HAITF will continue in disease states, associated with abnormal iron homeostasis. This project will not only assess the significance of this compound as an iron transport mechanism, but should provide new insight into the regulation of iron metabolism and mechanisms associated with abnormal iron homeostasis.