Identification of an S-adenosylmethionine (SAM) dependent arsenic methyltransferase in Danio rerio.

Toxicology and Applied Pharmacology
Mohamad HamdiZijuan Liu

Abstract

Arsenic methylation is an important cellular metabolic process that modulates arsenic toxicity and carcinogenicity. Biomethylation of arsenic produces a series of mono-, di- and tri-methylated arsenic metabolites that can be detected in tissues and excretions. Here we report that zebrafish exposed to arsenite (As(III)) produces organic arsenicals, including MMA(III), MMA(V) and DMA(V) with characteristic tissue ratios, demonstrating that an arsenic methylation pathway exists in zebrafish. In mammals, cellular inorganic arsenic is methylated by a SAM-dependent arsenic methyltransferase, AS3MT. A zebrafish arsenic methyltransferase homolog, As3mt, was identified by sequence alignment. Western blotting analysis showed that As3mt was universally expressed in zebrafish tissues. Prominent expression in liver and intestine correlated with methylated arsenic metabolites detected in those tissues. As3mt was expressed in and purified from Escherichia coli for in vitro functional studies. Our results demonstrated that As3mt methylated As(III) to DMA(V) as an end product and produced MMA(III) and MMA(V) as intermediates. The activity of As3mt was inhibited by elevated concentrations of the substrate As(III) as well as the metalloid selenit...Continue Reading

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Aug 31, 2014·Environmental Science and Pollution Research International·Jorke H KamstraJuliette Legler
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