Pathways of arsenic biotransformations: The arsenic methylation cycle

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

Pathways of arsenic biotransformations: The arsenic methylation cycle

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

Department of Atomic and Molecular Physics, Manipal

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

4 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 language	English
Title of host publication	Understanding the Geological and Medical Interface of Arsenic, As 2012 - 4th International Congress
Subtitle of host publication	Arsenic in the Environment
Pages	185-188
Number of pages	4
Publication status	Published - 16-08-2012
Event	4th International Congress on Arsenic in the Environment, As 2012 - Cairns, QLD, Australia Duration: 22-07-2012 → 27-07-2012

Conference

Conference	4th International Congress on Arsenic in the Environment, As 2012
Country/Territory	Australia
City	Cairns, QLD
Period	22-07-12 → 27-07-12

All Science Journal Classification (ASJC) codes

Environmental Chemistry
Pollution

Cite this

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title = "Pathways of arsenic biotransformations: The arsenic methylation cycle",

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 {\aa} 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.",

author = "B. Rosen and K. Marapakala and {Abdul Salam}, {A. A.} and C. Packianathan and M. Yoshinaga",

year = "2012",

month = aug,

day = "16",

language = "English",

isbn = "9780415637633",

pages = "185--188",

booktitle = "Understanding the Geological and Medical Interface of Arsenic, As 2012 - 4th International Congress",

note = "4th International Congress on Arsenic in the Environment, As 2012 ; Conference date: 22-07-2012 Through 27-07-2012",

}

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.

TY - GEN

T1 - Pathways of arsenic biotransformations

T2 - 4th International Congress on Arsenic in the Environment, As 2012

AU - Rosen, B.

AU - Marapakala, K.

AU - Abdul Salam, A. A.

AU - Packianathan, C.

AU - Yoshinaga, M.

PY - 2012/8/16

Y1 - 2012/8/16

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.

AB - 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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M3 - Conference contribution

AN - SCOPUS:84864874053

SN - 9780415637633

SP - 185

EP - 188

BT - Understanding the Geological and Medical Interface of Arsenic, As 2012 - 4th International Congress

Y2 - 22 July 2012 through 27 July 2012

ER -

Pathways of arsenic biotransformations: The arsenic methylation cycle

Abstract

Conference

All Science Journal Classification (ASJC) codes

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