Origin of the unusual kinetics of iron deposition in human H-chain ferritin
Origin of the unusual kinetics of iron deposition in human H-chain ferritin
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DOI：
10.1021/ja044355k
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发表时间：
2005-03-23
影响因子：
15
通讯作者：
Chasteen, ND
中科院分区：
文献类型：
--
作者：
Bou-Abdallah, F;Zhao, GH;Chasteen, ND
从微生物到人类，铁蛋白在铁的生物管理中起着核心作用。铁蛋白通过在其壳状结构内氧化沉积铁作为含水氢氧化铁矿物核，发挥铁储存和解毒蛋白质的作用。矿物岩心形成的机制多年来一直是人们深入研究的课题。位于脊椎动物铁蛋白h链亚基上的二铁氧化酶位点催化铁（II）被分子氧氧化为铁（III）。先前对在该位点形成的瞬态过氧化物（III）中间体的停流动力学研究揭示了非常不寻常的动力学曲线，其形状明显取决于提供给蛋白质的铁的量。在目前的工作中，建立了一个催化的数学模型来解释观察到的动力学。该模型由两个顺序机制组成。在第一种机制中，铁在氧化铁酶位点的周转很快，导致过氧化物中间体的稳态生产，并不断形成矿物核，直到溶液中可用的铁（II）被消耗掉。在这一点上，第二种机制开始发挥作用，即过氧化物中间体衰变和铁氧化酶位点被假定为空出其铁补体。动力学数据首次揭示，超过铁氧化酶位点饱和所需的铁（II）可促进该位点的铁（III）快速周转，并且铁氧化酶位点在蛋白质的所有铁负载水平（48-800 Fe/protein）中起催化作用。该数据还为第二种中间体提供了证据，即一种假定的氢过氧化物（III）配合物，它是过氧化物中间体的衰变产物。
From microorganisms to humans, ferritin plays a central role in the biological management of iron. The ferritins function as iron storage and detoxification proteins by oxidatively depositing iron as a hydrous ferric hydroxide mineral core within their shell-like structures. The mechanism by which the mineral core is formed has been the subject of intense investigation for many years. A diiron ferroxidase site located on the H-chain subunit of vertebrate ferritins catalyzes the oxidation of Fe(II) to Fe(III) by molecular oxygen. A previous stopped-flow kinetics study of a transient mu-peroxodise(III) intermediate formed at this site revealed very unusual kinetics curves, the shape of which depended markedly on the amount of iron presented to the protein.(17) In the present work, a mathematical model for catalysis is developed that explains the observed kinetics. The model consists of two sequential mechanisms. In the first mechanism, turnover of iron at the ferroxidase site is rapid, resulting in steady-state production of the peroxo intermediate with continual formation of the mineral core until the available Fe(II) in solution is consumed. At this point, the second mechanism comes into play whereby the peroxo intermediate decays and the ferroxidase site is postulated to vacate its complement of iron. The kinetic data reveal for the first time that Fe(II) in excess of that required to saturate the ferroxidase site promotes rapid turnover of Fe(III) at this site and that the ferroxidase site plays a role in catalysis at all levels of iron loading of the protein (48-800 Fe/protein). The data also provide evidence for a second intermediate, a putative hydroperoxodise(III) complex, that is a decay product of the peroxo intermediate.