Brissot P, Wright T L, Ma W L, Weisiger R A
J Clin Invest. 1985 Oct;76(4):1463-70. doi: 10.1172/JCI112125.
In hemochromatosis and other disorders associated with iron overload, a significant fraction of the total iron in plasma circulates in the form of low molecular weight complexes not bound to transferrin. Efficient and unregulated clearance of this form of iron by the liver may account for the hepatic iron loading and toxicity that characterize these diseases. We tested this possibility by examining the hepatic removal process for representative iron complexes in the single-pass perfused rat liver. Hepatic uptake of both ferrous and ferric 55Fe from ultrafiltered human serum was found to be highly efficient and effectively irreversible (single-pass extraction of 1 microM iron, 58-75%). Similar high efficiencies were seen for iron complexed to specific physiologic and nonphysiologic coordinators, including histidine, citrate, fructose, oxalate and glutamate, and tricine. Because of lower plasma flow rates, single-pass extraction of these iron complexes in vivo should be even greater. Autoradiography confirmed that most iron had been removed by parenchymal cells. Hepatic removal from Krebs-tricine buffer was saturable with similar kinetic parameters for ferrous and ferric iron (apparent Km, 14-22 microM; V max, 24-38 nmol min-1 g liver-1). These findings suggest that high levels of non-transferrin-bound iron in plasma may be an important cause of hepatic iron loading in iron overload states.
在血色素沉着症及其他与铁过载相关的疾病中，血浆中相当一部分总铁以未与转铁蛋白结合的低分子量复合物形式循环。肝脏对这种形式的铁进行高效且不受调控的清除，可能是这些疾病所特有的肝脏铁负荷及毒性的原因。我们通过研究单次灌注大鼠肝脏中代表性铁复合物的肝脏清除过程来检验这种可能性。发现从超滤人血清中摄取亚铁和铁55Fe的效率都很高且实际上是不可逆的（1 microM铁的单次通过提取率为58 - 75%）。对于与特定生理和非生理配位体络合的铁，包括组氨酸、柠檬酸盐、果糖、草酸盐、谷氨酸盐以及三（羟甲基）甲基甘氨酸，也观察到了类似的高效率。由于体内血浆流速较低，这些铁复合物在体内的单次通过提取率应该更高。放射自显影证实大部分铁已被实质细胞清除。从Krebs - 三（羟甲基）甲基甘氨酸缓冲液中进行肝脏清除对于亚铁和铁具有相似的动力学参数且具有饱和性（表观Km为14 - 22 microM；Vmax为24 - 38 nmol min-1 g肝脏-1）。这些发现表明，血浆中高水平的非转铁蛋白结合铁可能是铁过载状态下肝脏铁负荷的一个重要原因。
