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A direct comparison of divalent metal-ion transporter (DMT1) and hinokitiol, a potential small molecule replacement.
Biometals ( IF 4.1 ) Pub Date : 2019-07-31 , DOI: 10.1007/s10534-019-00207-2
Michael D Garrick 1, 2 , Laura M Garrick 1 , Lin Zhao 1 , James F Collins 3 , Joleen Soukup 4 , Andrew J Ghio 4
Affiliation  

Hinokitiol, a natural lipophilic chelator, appears capable of replacing several iron transporters after they have been genetically ablated. Divalent metal-ion transporter (DMT1) is the major iron importer in enterocytes and erythroblasts. We have compared DMT1 and hinokitiol in multiple fashions to learn if the smaller molecule is a suitable substitute using two HEK293 cell lines engineered to overexpress different isoforms of DMT1. Both the macromolecule and the lipophilic chelator enable import of ferrous ions into HEK293 cells. Hinokitiol also mediates ferric ion import but DMT1 cannot do so. While DMT1 can also import Mn2+ ions, hinokitiol lacks this ability. The Michaelis-Menten analysis for kinetics of macromolecular catalysis is also suitable for hinokitiol-supported iron import. To compare hinokitiol to DMT1 relative to other metal ions that DMT1 can transport, we employed an organic extraction procedure with which we initially matched the results obtained for Fe2+, Fe3+ and Mn2+, and then showed that multiple other cations were unlikely to enter via hinokitiol. The small chelator thus shares some functional properties with DMT1, but distinct difference were also noted.

中文翻译:

直接比较二价金属离子转运蛋白(DMT1)和扁柏酚,一种潜在的小分子替代物。

Hinokitiol是一种天然的亲脂性螯合剂,经过基因消融后,似乎能够替代几种铁转运蛋白。二价金属离子转运蛋白(DMT1)是肠上皮细胞和成红细胞中主要的铁进口者。我们已经以多种方式比较了DMT1和扁柏酚,以了解较小的分子是否适合使用两种工程改造为过表达DMT1不同异构体的HEK293细胞系。大分子和亲脂性螯合剂均可将亚铁离子导入HEK293细胞。Hinokitiol也介导铁离子的导入,但DMT1不能这样做。虽然DMT1也可以导入Mn2 +离子,但是扁柏酚缺乏这种能力。Michaelis-Menten对大分子催化动力学的分析也适用于由扁柏酚支撑的铁的进口。为了相对于DMT1可以转运的其他金属离子比较扁柏酚与DMT1,我们采用了有机萃取程序,我们首先将获得的Fe2 +,Fe3 +和Mn2 +的结果进行了匹配,然后表明其他多种阳离子不太可能通过扁柏酚进入。因此,小螯合剂与DMT1具有一些功能特性,但也注意到了明显的差异。
更新日期:2019-07-31
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