Liu Zijuan, Sanchez Marco A, Jiang Xuan, Boles Eckhard, Landfear Scott M, Rosen Barry P
Department of Biochemistry and Molecular Biology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
Biochem Biophys Res Commun. 2006 Dec 15;351(2):424-30. doi: 10.1016/j.bbrc.2006.10.054. Epub 2006 Oct 17.
Arsenic exposure is associated with hypertension, diabetes, and cancer. Some mammals methylate arsenic. Saccharomyces cerevisiae hexose permeases catalyze As(OH)(3) uptake. Here, we report that mammalian glucose transporter GLUT1 catalyzes As(OH)(3) and CH(3)As(OH)(2) uptake in yeast or in Xenopus laevis oocytes. Expression of GLUT1 in a yeast lacking other glucose transporters allows for growth on glucose. Yeast expressing yeast HXT1 or rat GLUT1 transport As(OH)(3) and CH(3)As(OH)(2). The K(m) of GLUT1 is to 1.2mM for CH(3)As(OH)(2), compared to a K(m) of 3mM for glucose. Inhibition between glucose and CH(3)As(OH)(2) is noncompetitive, suggesting differences between the translocation pathways of hexoses and arsenicals. Both human and rat GLUT1 catalyze uptake of both As(OH)(3) and CH(3)As(OH)(2) in oocytes. Thus GLUT1 may be a major pathway uptake of both inorganic and methylated arsenicals in erythrocytes or the epithelial cells of the blood-brain barrier, contributing to arsenic-related cardiovascular problems and neurotoxicity.
砷暴露与高血压、糖尿病和癌症有关。一些哺乳动物会使砷甲基化。酿酒酵母己糖转运蛋白催化亚砷酸（As(OH)(3)）的摄取。在此，我们报告哺乳动物葡萄糖转运蛋白1（GLUT1）在酵母或非洲爪蟾卵母细胞中催化亚砷酸（As(OH)(3)）和甲基亚砷酸（CH(3)As(OH)(2)）的摄取。在缺乏其他葡萄糖转运蛋白的酵母中表达GLUT1可使其在葡萄糖上生长。表达酵母己糖转运蛋白1（HXT1）或大鼠GLUT1的酵母可转运亚砷酸（As(OH)(3)）和甲基亚砷酸（CH(3)As(OH)(2)）。GLUT1对甲基亚砷酸（CH(3)As(OH)(2)）的米氏常数（K(m)）为1.2mM，而对葡萄糖的米氏常数为3mM。葡萄糖与甲基亚砷酸（CH(3)As(OH)(2)）之间的抑制作用是非竞争性的，这表明己糖和砷化合物的转运途径存在差异。人源和大鼠源的GLUT1均在卵母细胞中催化亚砷酸（As(OH)(3)）和甲基亚砷酸（CH(3)As(OH)(2)）的摄取。因此，GLUT1可能是红细胞或血脑屏障上皮细胞摄取无机砷和甲基化砷化合物的主要途径，这可能导致与砷相关的心血管问题和神经毒性。
