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Profiling of Methyltransferases and Other S-adenosyl-L-homocysteine-binding Proteins by Capture Compound Mass Spectrometry CCMS
Published on: December 20, 2010
As(III) S-adenosylmethionine methyltransferases and other arsenic binding proteins
A Abdul Ajees1, Barry P Rosen2
1Department of Atomic and Molecular Physics, LG-01, Academic Block -5, MIT Campus, Manipal University, Manipal - 576 104, Karnataka, India.
Abstract:
Efflux is by far the most common means of arsenic detoxification is by methylation catalyzed by a family of As(III) S-adenosylmethionine (SAM) methyltransferases (MTs) enzymes designated ArsM in microbes or AS3MT in higher eukaryotes. The protein sequence of more than 5000 AS3MT/ArsM orthologues have been deposited in the NCBI database, mostly in prokaryotic and eukaryotic microbes. As(III) SAM MTs are members of a large superfamily of MTs involved in numerous physiological functions. ArsMs detoxify arsenic by conversion of inorganic trivalent arsenic (As(III)) into mono-, di- and trimethylated species that may be more toxic and carcinogenic than inorganic arsenic. The pathway of methylation remains controversial. Several hypotheses will be examined in this review.
Insights
Arsenic detoxification occurs via methylation by arsenic methyltransferase (AS3MT/ArsM) enzymes. This review examines the controversial methylation pathway and its implications for arsenic toxicity and carcinogenicity.
Area of Science:
- Biochemistry
- Environmental Toxicology
- Molecular Biology
Background:
- Arsenic detoxification primarily occurs through methylation catalyzed by arsenic methyltransferase (AS3MT/ArsM) enzymes.
- AS3MT/ArsM enzymes are part of a larger methyltransferase superfamily with diverse physiological roles.
- Over 5000 AS3MT/ArsM orthologues are documented in the NCBI database, predominantly in microbial organisms.
Purpose of the Study:
- To review the biochemical mechanisms of arsenic methylation.
- To examine the controversial pathway of arsenic methylation by AS3MT/ArsM enzymes.
- To discuss the potential toxicity and carcinogenicity of methylated arsenic species.
Main Methods:
- Literature review of existing research on AS3MT/ArsM enzymes.
- Analysis of protein sequence data from the NCBI database.
- Examination of various hypotheses regarding the arsenic methylation pathway.
Main Results:
- Arsenic detoxification involves the conversion of inorganic arsenic (As(III)) into methylated forms by AS3MT/ArsM.
- Methylated arsenic species may exhibit increased toxicity and carcinogenicity compared to inorganic arsenic.
- The precise methylation pathway remains a subject of ongoing scientific debate.
Conclusions:
- AS3MT/ArsM enzymes play a critical role in arsenic metabolism and detoxification across various organisms.
- Understanding the methylation pathway is crucial for assessing the health risks associated with arsenic exposure.
- Further research is needed to resolve the controversies surrounding the arsenic methylation pathway.
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