Journal of Biological Chemistry
Volume 275, Issue 43, 27 October 2000, Pages 33404-33408
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MEMBRANE TRANSPORT STRUCTURE FUNCTION AND BIOGENESIS
The MRP2/cMOAT Transporter and Arsenic-Glutathione Complex Formation Are Required for Biliary Excretion of Arsenic*

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Worldwide, millions of people are exposed to arsenic in drinking water that exceeds the World Health Organization standard of 10 μg/liter by as much as 50–300-fold, yet little is known about the molecular basis for arsenic excretion. Here we show that transport of arsenic into bile depends on the MRP2/cMOAT transporter and that glutathione is obligatory for such transport. Using reversed phase liquid chromatography/mass spectrometry, we demonstrate that two arsenic-glutathione complexes not previously identified in vivo, arsenic triglutathione and methylarsenic diglutathione, account for most of the arsenic in the bile. The structure of the compounds was also confirmed by nuclear magnetic resonance spectroscopy. Our findings may help explain the increased susceptibility of malnourished human populations to arsenic.

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Published, JBC Papers in Press, August 9, 2000, DOI 10.1074/jbc.M007030200

*

This work was supported by National Institutes of Health Grant ES 10389.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.