Umbreit Jay N, Conrad Marcel E, Hainsworth Lucille N, Simovich Marcia
University of South Alabama Cancer Center, Mobile, Alabama 36688, USA.
Am J Physiol Gastrointest Liver Physiol. 2002 Mar;282(3):G534-9. doi: 10.1152/ajpgi.00199.2001.
Inorganic iron can be transported into cells in the absence of transferrin. Ferric iron enters cells utilizing an integrin-mobilferrin-paraferritin pathway, whereas ferrous iron uptake is facilitated by divalent metal transporter-1 (DMT-1). Immunoprecipitation studies using antimobilferrin antibody precipitated the previously described large-molecular-weight protein complex named paraferritin. It was previously shown that paraferritin functions as an intracellular ferrireductase, reducing ferric iron to ferrous iron utilizing NADPH as the energy source. It functions in the pathway for the cellular uptake of ferric iron. This multipeptide protein contains a number of active peptides, including the ferric iron binding protein mobilferrin and a flavin monooxygenase. The immunoprecipitates and purified preparations of paraferritin also contained DMT-1. This identifies DMT-1 as one of the peptides constituting the paraferritin complex. Since paraferritin functions to reduce newly transported ferric iron to ferrous iron and DMT-1 can transport ferrous iron, these findings suggest a role for DMT-1 in conveyance of iron from paraferritin to ferrochelatase, the enzyme utilizing ferrous iron for the synthesis of heme in the mitochondrion.
在没有转铁蛋白的情况下，无机铁可以转运进入细胞。三价铁利用整合素-运铁蛋白-副铁蛋白途径进入细胞，而二价金属转运体1（DMT-1）促进二价铁的摄取。使用抗运铁蛋白抗体进行的免疫沉淀研究沉淀出了先前描述的名为副铁蛋白的大分子蛋白复合物。先前已表明，副铁蛋白作为一种细胞内铁还原酶，以NADPH作为能源将三价铁还原为二价铁。它在三价铁的细胞摄取途径中发挥作用。这种多聚肽蛋白包含许多活性肽，包括三价铁结合蛋白运铁蛋白和一种黄素单加氧酶。副铁蛋白的免疫沉淀物和纯化制剂中也含有DMT-1。这表明DMT-1是构成副铁蛋白复合物的肽之一。由于副铁蛋白的功能是将新转运的三价铁还原为二价铁，且DMT-1可以转运二价铁，这些发现提示DMT-1在铁从副铁蛋白转运至亚铁螯合酶（该酶在线粒体中利用二价铁合成血红素）的过程中发挥作用。
