Mathematical modeling of the dynamic storage of iron in ferritin.
Mathematical modeling of the dynamic storage of iron in ferritin.
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DOI：
10.1186/1752-0509-4-147
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发表时间：
2010-11-03
影响因子：
--
通讯作者：
Nuñez MT
中科院分区：
文献类型：
--
作者：
Salgado JC;Olivera-Nappa A;Gerdtzen ZP;Tapia V;Theil EC;Conca C;Nuñez MT
铁对于维持基本的细胞过程是必不可少的。在调节其细胞水平的过程中，铁蛋白是细胞内主要的铁储存蛋白。在这项工作中，我们提出了铁蛋白在肠道铁吸收过程中铁储存动力学的数学模型。考虑铁蛋白、铁和由各自铁含量定义的离散铁蛋白种群的主反应动力学表达式和质量平衡，建立了一组微分方程。模拟结果显示铁蛋白铁含量随铁脉冲的变化，并与体外培养不同铁水平纯化铁蛋白获得的铁蛋白铁分布的实验数据进行了比较。该模型成功捕获了实验观察到的不同特征，即铁在不同铁含量的铁蛋白纳米笼中的分布模式，以及铁蛋白作为胞质不稳定铁池（cLIP）的控制器的作用。铁蛋白可以在很大范围内稳定细胞内总铁浓度的cLIP，但该模型预测，当铁蛋白的存储容量超过铁蛋白的存储容量时，当铁蛋白的铁含量达到2500 Fe/铁蛋白时，cLIP会呈指数增长。这些结果支持铁蛋白在细胞系统中作为铁缓冲剂的作用。此外，该模型预测了缓冲蛋白的理想特性，如有效去除多余的铁，即使在引入大扰动时也能保持细胞内cLIP水平大致恒定，以及在缺铁情况下可自由获得的铁来源。此外，模拟的铁去除过程的动态非常快，铁蛋白作为第一道防御危险的铁波动的屏障，为细胞激活较慢的转录调节机制和适应铁胁迫条件提供了所需的时间。综上所述，该模型捕捉到了铁-铁蛋白平衡的复杂性，可以用于进一步的理论探索铁蛋白在调节细胞内不稳定铁水平中的作用，特别是在肠铁吸收过程中作为铁转运的相关调节剂。
Iron is essential for the maintenance of basic cellular processes. In the regulation of its cellular levels, ferritin acts as the main intracellular iron storage protein. In this work we present a mathematical model for the dynamics of iron storage in ferritin during the process of intestinal iron absorption. A set of differential equations were established considering kinetic expressions for the main reactions and mass balances for ferritin, iron and a discrete population of ferritin species defined by their respective iron content. Simulation results showing the evolution of ferritin iron content following a pulse of iron were compared with experimental data for ferritin iron distribution obtained with purified ferritin incubated in vitro with different iron levels. Distinctive features observed experimentally were successfully captured by the model, namely the distribution pattern of iron into ferritin protein nanocages with different iron content and the role of ferritin as a controller of the cytosolic labile iron pool (cLIP). Ferritin stabilizes the cLIP for a wide range of total intracellular iron concentrations, but the model predicts an exponential increment of the cLIP at an iron content > 2,500 Fe/ferritin protein cage, when the storage capacity of ferritin is exceeded. The results presented support the role of ferritin as an iron buffer in a cellular system. Moreover, the model predicts desirable characteristics for a buffer protein such as effective removal of excess iron, which keeps intracellular cLIP levels approximately constant even when large perturbations are introduced, and a freely available source of iron under iron starvation. In addition, the simulated dynamics of the iron removal process are extremely fast, with ferritin acting as a first defense against dangerous iron fluctuations and providing the time required by the cell to activate slower transcriptional regulation mechanisms and adapt to iron stress conditions. In summary, the model captures the complexity of the iron-ferritin equilibrium, and can be used for further theoretical exploration of the role of ferritin in the regulation of intracellular labile iron levels and, in particular, as a relevant regulator of transepithelial iron transport during the process of intestinal iron absorption.
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DOI：
10.1152/ajpgi.1997.273.3.g636
发表时间：
1997-09-01
影响因子：
4.5
作者：
Oates, PS;Morgan, EH
通讯作者：
Morgan, EH
DOI：
10.1111/j.1432-1033.1976.tb10569.x
发表时间：
1976-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
HUEBERS, H;HUEBERS, E;CRICHTON, RR
通讯作者：
CRICHTON, RR
DOI：
10.1049/ip-syb:20050104
发表时间：
2006-07-01
期刊：
IEE PROCEEDINGS SYSTEMS BIOLOGY
影响因子：
--
作者：
Flach, E. H.;Schnell, S.
通讯作者：
Schnell, S.
影响因子：
4.8
作者：
Abboud, S;Haile, DJ
通讯作者：
Haile, DJ
影响因子：
4.8
作者：
Liu, Xiaofeng S.;Patterson, Leslie D.;Theil, Elizabeth C.
通讯作者：
Theil, Elizabeth C.