Pathways of arsenic biotransformations: The arsenic methylation cycle

B. Rosen, K. Marapakala, A. A. Abdul Salam, C. Packianathan, M. Yoshinaga

Research output: Chapter in Book/Report/Conference proceedingConference contribution

2 Citations (Scopus)

Abstract

Arsenic methylation is catalyzed by the enzyme As(III)-S-adenosylmethionine methyltransferase (AS3MT or ArsM) that transfers up to three methyl groups from SAM to As(III), producing CH 3 As(III), (CH 3) 2MAs(III) and the nontoxic gaseous product (CH 3) 3MAs(III). In liver AS3MT methylates arsenic, which is excreted in urine. This biotransformation is thought to activate arsenic into a carcinogen. A thermophilic orthologue of human AS3MT was crystallized, and its x-ray crystal structure solved to 1.6 å with bound SAM or As(III). Our data support a pathway of methylation in which GSH conjugates are preferred substrates, and arsenic remains trivalent throughout the catalytic cycle. The location of polymorphisms were mapped onto a homology model of human AS3MT, giving insight into their biochemical effects. Finally, a new gene/enzyme that demethylates methylarsenicals was cloned/purified and characterized.

Original languageEnglish
Title of host publicationUnderstanding the Geological and Medical Interface of Arsenic, As 2012 - 4th International Congress
Subtitle of host publicationArsenic in the Environment
Pages185-188
Number of pages4
Publication statusPublished - 16-08-2012
Event4th International Congress on Arsenic in the Environment, As 2012 - Cairns, QLD, Australia
Duration: 22-07-201227-07-2012

Conference

Conference4th International Congress on Arsenic in the Environment, As 2012
CountryAustralia
CityCairns, QLD
Period22-07-1227-07-12

Fingerprint

Methylation
methylation
Arsenic
biotransformation
arsenic
Enzymes
enzyme
S-Adenosylmethionine
Carcinogens
Methyltransferases
carcinogen
Polymorphism
homology
crystal structure
Liver
urine
polymorphism
Genes
Crystal structure
substrate

All Science Journal Classification (ASJC) codes

  • Environmental Chemistry
  • Pollution

Cite this

Rosen, B., Marapakala, K., Abdul Salam, A. A., Packianathan, C., & Yoshinaga, M. (2012). Pathways of arsenic biotransformations: The arsenic methylation cycle. In Understanding the Geological and Medical Interface of Arsenic, As 2012 - 4th International Congress: Arsenic in the Environment (pp. 185-188)
Rosen, B. ; Marapakala, K. ; Abdul Salam, A. A. ; Packianathan, C. ; Yoshinaga, M. / Pathways of arsenic biotransformations : The arsenic methylation cycle. Understanding the Geological and Medical Interface of Arsenic, As 2012 - 4th International Congress: Arsenic in the Environment. 2012. pp. 185-188
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Rosen, B, Marapakala, K, Abdul Salam, AA, Packianathan, C & Yoshinaga, M 2012, Pathways of arsenic biotransformations: The arsenic methylation cycle. in Understanding the Geological and Medical Interface of Arsenic, As 2012 - 4th International Congress: Arsenic in the Environment. pp. 185-188, 4th International Congress on Arsenic in the Environment, As 2012, Cairns, QLD, Australia, 22-07-12.

Pathways of arsenic biotransformations : The arsenic methylation cycle. / Rosen, B.; Marapakala, K.; Abdul Salam, A. A.; Packianathan, C.; Yoshinaga, M.

Understanding the Geological and Medical Interface of Arsenic, As 2012 - 4th International Congress: Arsenic in the Environment. 2012. p. 185-188.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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N2 - Arsenic methylation is catalyzed by the enzyme As(III)-S-adenosylmethionine methyltransferase (AS3MT or ArsM) that transfers up to three methyl groups from SAM to As(III), producing CH 3 As(III), (CH 3) 2MAs(III) and the nontoxic gaseous product (CH 3) 3MAs(III). In liver AS3MT methylates arsenic, which is excreted in urine. This biotransformation is thought to activate arsenic into a carcinogen. A thermophilic orthologue of human AS3MT was crystallized, and its x-ray crystal structure solved to 1.6 å with bound SAM or As(III). Our data support a pathway of methylation in which GSH conjugates are preferred substrates, and arsenic remains trivalent throughout the catalytic cycle. The location of polymorphisms were mapped onto a homology model of human AS3MT, giving insight into their biochemical effects. Finally, a new gene/enzyme that demethylates methylarsenicals was cloned/purified and characterized.

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Rosen B, Marapakala K, Abdul Salam AA, Packianathan C, Yoshinaga M. Pathways of arsenic biotransformations: The arsenic methylation cycle. In Understanding the Geological and Medical Interface of Arsenic, As 2012 - 4th International Congress: Arsenic in the Environment. 2012. p. 185-188