APOFERRITIN AS A FERROXIDASE

最近发现，铁蛋白，铁的储存， 蛋白质，能够催化Fe（II）氧化为Fe（III）。 一些 对这种铁氧化酶进行了初步测定 活动，但一个更完整的表征动态 脱铁铁蛋白的作用是必需的。 此外，建议 这种观察到的酶活性代表了 铁蛋白铁掺入。 这里概述的研究计划是 针对铁氧化酶的广泛研究， 脱铁铁蛋白的活性及其在铁掺入中的可能作用。 具体目标是：（1）表征动力学和 铁氧化过程的分子性质（动力学 参数，底物特异性，抑制，氨基酸 修改）。 这将主要通过使用 通过铁结合捕获产物Fe（III）的方法 蛋白质，转铁蛋白;（2）研究分子方面的 铁氧化过程的机理（化学计量，O2和 其他电子受体作为氧化剂，O2还原的命运， （3）比较不同的辅因子， 脱铁铁蛋白作为铁氧化酶的特性及其功能 铁公司 尽管进行了大量的调查， 铁蛋白的铁储存和利用。 铁蛋白已被 作为铁代谢的关键分子， 血清铁蛋白浓度目前用于临床 监测铁水平/利用和疾病的情况 病症，包括缺铁性贫血，实体瘤， 白血病和重金属中毒 然而，在更多 临床上使用的是铁蛋白，我们必须有一个更大的 了解其在铁代谢中的动态作用。 结果 从拟议的研究将提供新的见解， 问题.

It has recently been discovered that ferritin, the iron storage protein, is able to catalyze the oxidation of Fe(II) to Fe(III). Some preliminary measurements have been made of this ferroxidase activity, but a more complete characterization of the dynamic action of apoferritin is essential. Furthermore, it is suggested that this observed enzymatic activity represents the first step in ferritin iron incorporation. The research plan outlined here is directed toward an extensive investigation of the ferroxidase activity of apoferritin and its possible role in iron incorporation. The specific aims are: (1) to characterize the kinetic and molecular properties of the ferroxidation process (kinetic parameters, substrate specificity, inhibition, amino acid modification). This will be achieved primarily by using a procedure for capture of the product, Fe(III), by the iron-binding protein, transferrin; (2) to investigate aspects of the molecular mechanism of the ferroxidation precess (stoichiometry, O2 and other electron acceptors as oxidants, fate of O2 reduction, identity of cofactor(s)); and (3) a comparison of the characteristics of apoferritin as a ferroxidase with its function iron incorporation. In spite of numerous investigations, little is known about the role of ferritin iron storage and utilization. Ferritin has been implicated as a key molecule in iron metabolism and the concentration of serum ferritin is currently used in clinical situations to monitor iron levels/utilization and disease conditions, including iron deficiency anaemia, solid tumors, leukemia, and heavy metal toxicity. However, before more clinical use is made of ferritin, we must have a greater understanding of its dynamic role in iron metabolism. Results from the proposed research will provide new insight into this problem.