Origin of the Unusual Kinetics of Iron Deposition in Human H-Chain Ferritin
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- 作者：Fadi Bou-Abdallah ; Guanghua Zhao ; Howard R. Mayne ; Paolo Arosio ; and N. Dennis Chasteen
- 刊名：Journal of the American Chemical Society
- 出版年：2005
- 出版时间：March 23, 2005
- 年：2005
- 卷：127
- 期：11
- 页码：3885 - 3893
- 全文大小：267K
- 年卷期：v.127,no.11(March 23, 2005)
- ISSN：1520-5126
文摘
From microorganisms to humans, ferritin plays a central role in the biological management ofiron. The ferritins function as iron storage and detoxification proteins by oxidatively depositing iron as ahydrous ferric hydroxide mineral core within their shell-like structures. The mechanism by which the mineralcore is formed has been the subject of intense investigation for many years. A diiron ferroxidase site locatedon 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 
-peroxodiFe(III) intermediate formed at this siterevealed very unusual kinetics curves, the shape of which depended markedly on the amount of ironpresented to the protein.17 In the present work, a mathematical model for catalysis is developed that explainsthe observed kinetics. The model consists of two sequential mechanisms. In the first mechanism, turnoverof iron at the ferroxidase site is rapid, resulting in steady-state production of the peroxo intermediate withcontinual formation of the mineral core until the available Fe(II) in solution is consumed. At this point, thesecond mechanism comes into play whereby the peroxo intermediate decays and the ferroxidase site ispostulated to vacate its complement of iron. The kinetic data reveal for the first time that Fe(II) in excessof that required to saturate the ferroxidase site promotes rapid turnover of Fe(III) at this site and that theferroxidase site plays a role in catalysis at all levels of iron loading of the protein (48-800 Fe/protein). Thedata also provide evidence for a second intermediate, a putative hydroperoxodiFe(III) complex, that is adecay product of the peroxo intermediate.
-peroxodiFe(III) intermediate formed at this siterevealed very unusual kinetics curves, the shape of which depended markedly on the amount of ironpresented to the protein.17 In the present work, a mathematical model for catalysis is developed that explainsthe observed kinetics. The model consists of two sequential mechanisms. In the first mechanism, turnoverof iron at the ferroxidase site is rapid, resulting in steady-state production of the peroxo intermediate withcontinual formation of the mineral core until the available Fe(II) in solution is consumed. At this point, thesecond mechanism comes into play whereby the peroxo intermediate decays and the ferroxidase site ispostulated to vacate its complement of iron. The kinetic data reveal for the first time that Fe(II) in excessof that required to saturate the ferroxidase site promotes rapid turnover of Fe(III) at this site and that theferroxidase site plays a role in catalysis at all levels of iron loading of the protein (48-800 Fe/protein). Thedata also provide evidence for a second intermediate, a putative hydroperoxodiFe(III) complex, that is adecay product of the peroxo intermediate.