CHEMISTRY AND METABOLISM OF A MAMMALIAN SIDEROPHOR

铁是生物圈中最丰富的金属之一，是一种重要的金属 大多数生物系统的营养物质。 由于 Fe(II) 的特性， Fe(III) 氧化还原电位铁参与广泛的关键反应 生化反应。 大多数（如果不是全部）生物体都进化出了复杂的 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， 结合铁并促进生物体的生长。 在高等动物中，铁 转运蛋白和铁蛋白等运输和储存蛋白 特征良好。 然而，中间的特征还没有得到很好的表征 转铁蛋白、铁蛋白和其他铁位点之间的铁转运系统 沉积。 可以实现此功能的低分子量配体 高等动物中的这种现象已被假设但尚未确定。 我们有 鉴定并纯化了大约 1500 分子量的肽 显示铁载体活性。 这种化合物，宿主相关铁 转移因子（HAITF）是从哺乳动物组织中分离出来的 显示可通过铁转运促进革兰氏阴性菌的生长 机制。 该提案概述了进一步表征的计划 该化合物的化学性质和代谢意义。 研究是 旨在确定主要结构、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，HAITF的研究还将继续 在疾病状态下，与铁稳态异常有关。 这个项目 不仅会评估该化合物作为铁运输的重要性 机制，但应该为铁的调节提供新的见解 与铁稳态异常相关的代谢和机制。

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.