The MRP2/cMOAT transporter and arsenic-glutathione complex formation are required for biliary excretion of arsenic

Worldwide, millions of people are exposed to arsenic in drinking water that exceeds the World Health Organization standard of 10 mug/liter by as much as 50-300-fold, yet little is known about the molecular basis for arsenic e xcretion. Here me show that transport of arsenic into bile depends on the M RP2/cMOAT transporter and that glutathione is obligatory for such transport , Using reversed phase liquid chromatography/mass spectrometry, we demonstr ate that two arsenic-glutathione complexes not previously identified in viv o, arsenic tri-glutathione and methylarsenic diglutathione, account for mos t of the arsenic in the bile. The structure of the compounds was also confi rmed by nuclear magnetic resonance spectroscopy, Our findings may help expl ain the increased susceptibility of malnourished human populations to arsen ic.