Nature of non-transferrin-bound iron: studies on iron citrate complexes and thalassemic sera
Nature of non-transferrin-bound iron: studies on iron citrate complexes and thalassemic sera
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DOI：
10.1007/s00775-007-0297-8
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发表时间：
2008-01-01
影响因子：
3
通讯作者：
Hider, Robert C.
中科院分区：
文献类型：
--
作者：
Evans, Robert W.;Rafique, Roozina;Hider, Robert C.
尽管其在铁超载疾病中的重要性，但对血浆非转铁蛋白结合铁（NTBI）的组成知之甚少。使用30 kDa超滤，地中海贫血患者的血浆由可过滤和不可过滤的NTBI组成，可过滤部分代表小于10%的NTBI。低过滤性可能由蛋白质结合或NTBI物质超过30 kDa导致。因此，研究了柠檬酸铁的性质及其与白蛋白的相互作用，因为这些可能代表NTBI物质。铁渗透5-或12-kDa的超滤单位完全复合物新鲜制备时，柠檬酸超过铁的10倍，而与30-kDa的超滤单位，渗透接近100%，在所有的摩尔比。一个g = 4.3的电子顺磁共振信号，单核铁的特征，是可检测的，只有与铁柠檬酸盐的比例高于1：100。去铁胺和1，2-二甲基-3-羟基吡啶-4-酮螯合柠檬酸铁络合物中的铁的能力也随着柠檬酸盐与铁的比率的增加而增加。因此，柠檬酸盐的摩尔过量增加有利于可螯合的较低分子量铁低聚物、二聚物和最终单体的逐渐出现。在存在白蛋白的情况下过滤柠檬酸铁显示出在广泛的铁与柠檬酸盐比率范围内与白蛋白的大量结合，并且还增加了铁对螯合剂的可及性，反映了向较小的低聚物种类的转变。然而，在体外实验中使用免疫耗竭或吸收白蛋白的汽巴蓝-琼脂糖凝胶表明，铁只是松散地结合在铁柠檬酸盐-白蛋白复合物和NTBI是不太可能的白蛋白结合到任何显着的程度在地中海贫血血清。
Despite its importance in iron-overload diseases, little is known about the composition of plasma non-transferrin-bound iron (NTBI). Using 30-kDa ultrafiltration, plasma from thalassemic patients consisted of both filterable and non-filterable NTBI, the filterable fraction representing less than 10% NTBI. Low filterability could result from protein binding or NTBI species exceeding 30 kDa. The properties of iron citrate and its interaction with albumin were therefore investigated, as these represent likely NTBI species. Iron permeated 5- or 12-kDa ultrafiltration units completely when complexes were freshly prepared and citrate exceeded iron by tenfold, whereas with 30-kDa ultrafiltration units, permeation approached 100% at all molar ratios. A g = 4.3 electron paramagnetic resonance signal, characteristic of mononuclear iron, was detectable only with iron-to-citrate ratios above 1:100. The ability of both desferrioxamine and 1,2-dimethyl-3-hydroxypyridin-4-one to chelate iron in iron citrate complexes also increased with increasing ratios of citrate to iron. Incremental molar excesses of citrate thus favour the progressive appearance of chelatable lower molecular weight iron oligomers, dimers and ultimately monomers. Filtration of iron citrate in the presence of albumin showed substantial binding to albumin across a wide range of iron-to-citrate ratios and also increased accessibility of iron to chelators, reflecting a shift towards smaller oligomeric species. However, in vitro experiments using immunodepletion or absorption of albumin to Cibacron blue-Sepharose indicate that iron is only loosely bound in iron citrate-albumin complexes and that NTBI is unlikely to be albumin-bound to any significant extent in thalassemic sera.