Mammalian glucose permease GLUT1 facilitates transport of arsenic trioxide and methylarsonous acid.

Abstract

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.

• Authors: Zijuan Liu, Marco A Sanchez, Xuan Jiang, Eckhard Boles, Scott M Landfear, Barry P Rosen
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 351 Issue 2 Pg. 424-30 (Dec 15 2006) ISSN: 0006-291X [Print] United States
• PMID: 17064664 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Arsenicals
• Glucose Transport Proteins, Facilitative
• Glucose Transporter Type 1
• HXT1 protein, S cerevisiae
• Hexoses
• Monosaccharide Transport Proteins
• Oxides
• SLC2A1 protein, human
• Saccharomyces cerevisiae Proteins
• Slc2a1 protein, rat
• Colforsin
• Cytochalasin B
• monomethylarsonic acid
• Arsenic Trioxide

Topics

• Animals
• Arsenic Trioxide
• Arsenicals (metabolism)
• Biological Transport, Active
• Cloning, Molecular
• Colforsin (pharmacology)
• Cytochalasin B (pharmacology)
• Female
• Glucose Transport Proteins, Facilitative
• Glucose Transporter Type 1 (physiology)
• Hexoses (pharmacology)
• Humans
• In Vitro Techniques
• Monosaccharide Transport Proteins (metabolism)
• Oocytes (metabolism)
• Oxides (metabolism)
• Rats
• Saccharomyces cerevisiae (metabolism)
• Saccharomyces cerevisiae Proteins (metabolism)
• Xenopus laevis