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CHEMISTRY AND METABOLISM OF A MAMMALIAN SIDEROPHOR

哺乳动物铁载体的化学和代谢

基本信息

批准号：
3152292
负责人：
ROBERT L JONES
金额：
$ 11.15万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-04-01 至 1987-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3152292
关键词：
bioenergetics chelating agents ferritin hemoprotein homeostasis iron disorder iron metabolism macrophage orphan disease /drug transferrin

项目摘要

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.

铁是生物圈中含量最丰富的金属之一，是至关重要的对大多数生物系统都有营养。由于它的特性Fe(II)到 Fe(III)氧化还原电位铁参与了多种重要的生化反应。大多数，如果不是所有的生物体，都进化出了复杂的铁结合、运输和储存分子以维持铁动态平衡。微生物产生低分子铁载体，结合铁，促进生物体的生长。在高等动物中，铁转铁蛋白和铁蛋白等运输和储存蛋白很好的特点。然而，没有很好地描述的是中间体铁在转铁蛋白、铁蛋白和其他铁部位之间的转运系统证词。可实现这一功能的低分子量配体在高等动物中，已经假设了动物，但没有确定。我们有鉴定和纯化了一种约1500分子量的多肽它显示了铁载体的活动。这种化合物，与宿主相关的铁转移因子(HAITF)，是从哺乳动物组织中分离出来的，并已被通过铁的运输促进革兰氏阴性细菌的生长机制。这项提案概述了一项计划，以进一步描述该化合物的化学性质和代谢意义。研究是设计用来确定一级结构、光谱参数与铁结合有关，并阐明铁结合配体分子。新陈代谢研究旨在评估任何可能的作用在细胞内铁的运输中。最后，将继续对HAITF进行研究在疾病状态下，与铁稳态异常相关。这个项目不仅会评估这种化合物作为铁质运输工具的重要性机制，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。