Pathways of Arsenic Uptake and Efflux

Hung Chi Yang, Hsueh Liang Fu, Yung Feng Lin, Barry P. Rosen*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

159 Scopus citations

Abstract

Arsenic is the most prevalent environmental toxic substance and ranks first on the U.S. Environmental Protection Agency's Superfund List. Arsenic is a carcinogen and a causative agent of numerous human diseases. Paradoxically arsenic is used as a chemotherapeutic agent for treatment of acute promyelocytic leukemia. Inorganic arsenic has two biological important oxidation states: As(V) (arsenate) and As(III) (arsenite). Arsenic uptake is adventitious because the arsenate and arsenite are chemically similar to required nutrients. Arsenate resembles phosphate and is a competitive inhibitor of many phosphate-utilizing enzymes. Arsenate is taken up by phosphate transport systems. In contrast, at physiological pH, the form of arsenite is As(OH) 3 , which resembles organic molecules such as glycerol. Consequently, arsenite is taken into cells by aquaglyceroporin channels. Arsenic efflux systems are found in nearly every organism and evolved to rid cells of this toxic metalloid. These efflux systems include members of the multidrug resistance protein family and the bacterial exchangers Acr3 and ArsB. ArsB can also be a subunit of the ArsAB As(III)-translocating ATPase, an ATP-driven efflux pump. The ArsD metallochaperone binds cytosolic As(III) and transfers it to the ArsA subunit of the efflux pump. Knowledge of the pathways and transporters for arsenic uptake and efflux is essential for understanding its toxicity and carcinogenicity and for rational design of cancer chemotherapeutic drugs.

Original languageEnglish
Title of host publicationCurrent Topics in Membranes
PublisherAcademic Press Inc.
Pages325-358
Number of pages34
DOIs
StatePublished - 2012
Externally publishedYes

Publication series

NameCurrent Topics in Membranes
Volume69
ISSN (Print)1063-5823

Keywords

  • ATPase
  • Aquaglyceroporin
  • Arsenate
  • Arsenic
  • Arsenite
  • Metallochaperone

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