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MECHANISM OF IRON REMOVAL FROM TRANSFERRIN BY AMINOPHOSP

氨基磷从转铁蛋白中去除铁的机制

基本信息

批准号：
3446175
负责人：
WESLEY R HARRIS
金额：
$ 5万
依托单位：
UNIVERSITY OF IDAHO
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-08-06 至 1987-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3446175
关键词：
aminoacid aminophosphonate bicarbonates catechols iron disorder iron metabolism ligands phenols polyphosphates sickle cell anemia thalassemia transferrin

项目摘要

One of the puzzles of iron metabolism is the mechanism by which cells are so effective at removing ferric ion from the powerful iron chelating protein transferrin. The mechanism of iron release from transferrin is also highly relevant to the development of a more effective drug for the treatment of iron overload which afflicts victims of Beta-thalassemia and sickle cell anemia. Iron release to low molecular weight ligands has been studied for several types of ligands, including polyphosphates, hydroxamates, amino acids, and catechols, and conflicting mechanisms have been proposed. This project involves a systematic study of the kinetics of iron removal by a series of aminophosphonic acid and phenolic ligands. A major objective of this study is to distinguish between the two most prominent proposed mechanisms for iron removal. This involves a full evaluation of the reaction rate as a function of the concentration of both the competing ligand and bicarbonate, and the determination of the activation parameters for the rate constants for each ligand. In cases where saturation kinetics are observed, the hyperbolic dependence of the rate of iron removal on the concentration of the ligand will be established, and pseudo first order rate constants will be determined for the rate limiting step at high ligand concentrations. Rate constants will also be determined for iron removal from both N-terminal and C-terminal mono(ferric)transferrin. Spectra will also be recorded for mixtures of ferric-transferrin with monodentate ligands such as phosphate, phenol, and acetate to characterize any mixed-ligand complex which may form under conditions where no significant amount of iron removal will occur.

铁新陈代谢的谜题之一是细胞通过什么机制因此，有效地去除铁离子从强大的螯合铁离子蛋白质转铁蛋白。转铁蛋白释放铁的机制是也与开发一种更有效的治疗癌症的药物高度相关 β-地中海贫血患者铁负荷过重的治疗镰状细胞性贫血。铁向低分子量配体的释放研究了几种类型的配体，包括聚磷酸盐，异羟甲酸酯、氨基酸和儿茶酚，以及相互冲突的机制已被提出。该项目涉及到对除铁动力学的系统研究。一系列氨基膦酸类和酚类配体。一个主要目标这项研究的目的是区分两个最突出的建议除铁的机制。这涉及到对反应速率作为两个竞争对手浓度的函数配体和小苏打的作用及活化参数的测定得到了每个配体的速率常数。在饱和动力学的情况下都是观察到的，除铁速度的双曲线依赖于将建立配体的浓度，并将其伪一级对于高配基的速率限制步骤，将确定速率常数浓度。还将确定除铁的速率常数来自N端和C端的单(铁)转铁蛋白。还将记录铁-转铁蛋白与铁的混合物的光谱。单齿配体，如磷酸盐、苯酚和醋酸酯，以表征在不存在的条件下可以形成的任何混合配位络合物将会发生大量的除铁。