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 microg/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.
Departments of Pathology and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
S V
SV
Kala
M W
MW
Neely
G
G
Kala
C I
CI
Prater
D W
DW
Atwood
J S
JS
Rice
M W
MW
Lieberman
D000818:Animals; D027321:Anion Transport Proteins; D001151:Arsenic / Q000378:metabolism*; D001152:Arsenicals / Q000378:metabolism*; D001646:Bile / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000502:physiology*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D017208:Rats, Wistar
D027321:Anion Transport Proteins; D001152:Arsenicals; D002352:Carrier Proteins; C571174:methylarsenic diglutathione; D005978:Glutathione; D001151:Arsenic