ArticleChemical research in toxicology2014
Pathway of human AS3MT arsenic methylation.
Article in Chemical research in toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Provision of folic acid for reducing arsenic toxicity in arsenic-exposed children and adults.The Cochrane database of systematic reviews · 2021Pooled it
- Arsenic exposure and skin cancer: Mechanisms, clinical evidence and public health implications (Review).International journal of molecular medicine · 2026Review
- Synergistic function of ars genes in arsenic detoxification and biosynthesis of organoarsenicals.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Hepatotoxicity induced by arsenic trioxide: clinical features, mechanisms, preventive and potential therapeutic strategies.Frontiers in pharmacology · 2025Review
- A Computational Model of Endogenous Hydrogen Peroxide Metabolism in Hepatocytes, Featuring a Critical Role for GSH.Computational toxicology (Amsterdam, Netherlands) · 2024Article
- Temporal dynamics in a red alga dominated geothermal feature in Yellowstone National Park.ISME communications · 2024Article
- Two-tiered mutualism improves survival and competitiveness of cross-feeding soil bacteria.The ISME journal · 2023Article
- Effects of Dietary Intake of Arsenosugars and Other Organic Arsenic Species on Studies of Arsenic Methylation Efficiency in Humans.Environment & health (Washington, D.C.) · 2023Review
- Impact of lowering the US maximum contaminant level on arsenic exposure: Differences by race, region, and water arsenic in NHANES 2003-2014.Environmental pollution (Barking, Essex : 1987) · 2023Article
- Cross-sectional associations between drinking water arsenic and urinary inorganic arsenic in the United States: NHANES 2003-2014.Environmental research · 2023Article
- Arsenic in medicine: past, present and future.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Review
- ArsZ from Ensifer adhaerens ST2 is a novel methylarsenite oxidase.Environmental microbiology · 2022Article
- Functional characterization of the schizophrenia associated gene AS3MT identifies a role in neuronal development.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2022Article
- Arsenic Exposure through Dietary Intake and Associated Health Hazards in the Middle East.Nutrients · 2022Review
- Arsenic 3 methyltransferase (AS3MT) automethylates on cysteine residues in vitro.Archives of toxicology · 2022Article
- Glutathione Is Involved in the Reduction of Methylarsenate to Generate Antibiotic Methylarsenite in Enterobacter sp. Strain CZ-1.Applied and environmental microbiology · 2022Article
- Differential metabolism of arsenicals regulates Fps1-mediated arsenite transport.The Journal of cell biology · 2022Article
- Functional characterization of the methylarsenite-inducible arsRM operon from Noviherbaspirillum denitrificans HC18.Environmental microbiology · 2022Article
- Organoarsenical tolerance in Sphingobacterium wenxiniae, a bacterium isolated from activated sludge.Environmental microbiology · 2022Article
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Abstract
A synthetic gene encoding human As(III) S-adenosylmethionine (SAM) methyltransferase (hAS3MT) was expressed, and the purified enzyme was characterized. The synthetic enzyme is considerably more active than a cDNA-expressed enzyme using endogenous reductants thioredoxin (Trx), thioredoxin reductase (TR), NADPH, and reduced glutathione (GSH). Each of the seven cysteines (the four conserved residues, Cys32, Cys61, Cys156, and Cys206, and nonconserved, Cys72, Cys85, and Cys250) was individually changed to serine. The nonconserved cysteine derivates were still active. None of the individual C32S, C61S, C156S, and C206S derivates were able to methylate As(III). However, the C32S and C61S enzymes retained the ability to methylate MAs(III). These observations suggest that Cys156 and Cys206 play a different role in catalysis than that of Cys32 and Cys61. A homology model built on the structure of a thermophilic orthologue indicates that Cys156 and Cys206 form the As(III) binding site, whereas Cys32 and Cys61 form a disulfide bond. Two observations shed light on the pathway of methylation. First, binding assays using the fluorescence of a single-tryptophan derivative indicate that As(GS)3 binds to the enzyme much faster than inorganic As(III). Second, the major product of the first round of methylation is MAs(III), not MAs(V), and remains enzyme-bound until it is methylated a second time. We propose a new pathway for hAS3MT catalysis that reconciles the hypothesis of Challenger ((1947) Sci. Prog., 35, 396-416) with the pathway proposed by Hayakawa et al. ((2005) Arch. Toxicol., 79, 183-191). The products are the more toxic and more carcinogenic trivalent methylarsenicals, but arsenic undergoes oxidation and reduction as enzyme-bound intermediates.
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