Document Detail


Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotype.
MedLine Citation:
PMID:  15808521     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inorganic arsenic is enzymatically methylated; hence, its ingestion results in exposure to the parent compound and various methylated arsenicals. Both experimental and epidemiological evidences suggest that some of the adverse health effects associated with chronic exposure to inorganic arsenic may be mediated by these methylated metabolites. If iAs methylation is an activation process, then the phenotype for inorganic arsenic methylation may determine risk associated with exposure to this metalloid. We examined inorganic arsenic methylation phenotypes and arsenic (+3 oxidation state) methyltransferase genotypes in four species: three that methylate inorganic arsenic (human (Homo sapiens), rat (Rattus norwegicus), and mouse (Mus musculus)) and one that does not methylate inorganic arsenic (chimpanzee, Pan troglodytes). The predicted protein products from arsenic (+3 oxidation state) methyltransferase are similar in size for rat (369 amino acid residues), mouse (376 residues), and human (375 residues). By comparison, a 275-nucleotide deletion beginning at nucleotide 612 in the chimpanzee gene sequence causes a frameshift that leads to a nonsense mutation for a premature stop codon after amino acid 205. The null phenotype for inorganic arsenic methylation in the chimpanzee is likely due to the deletion in the gene for arsenic (+3 oxidation state) methyltransferase that yields an inactive truncated protein. This lineage-specific loss of function caused by the deletion event must have occurred in the Pan lineage after Homo-Pan divergence about 5 million years ago.
Authors:
Jiaxin Li; Stephen B Waters; Zuzana Drobna; Vicenta Devesa; Miroslav Styblo; David J Thomas
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  204     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-04-05     Completed Date:  2005-05-20     Revised Date:  2009-10-01    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  164-9     Citation Subset:  IM    
Affiliation:
Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arsenic / metabolism*
Base Sequence / genetics
Chromosomes, Human, Pair 8 / genetics
Cysteine / chemistry,  genetics
Evolution, Molecular
Gene Deletion
Gene Expression Profiling / methods
Genotype
Humans
Methylation*
Methyltransferases / genetics*,  metabolism*
Mice
Models, Molecular
Molecular Sequence Data
Oxidation-Reduction
Pan troglodytes / genetics,  metabolism
Phenotype*
Rats
Species Specificity
Time Factors
Grant Support
ID/Acronym/Agency:
DK 56350/DK/NIDDK NIH HHS; ES010845/ES/NIEHS NIH HHS; R01 ES010845-05/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
52-90-4/Cysteine; 7440-38-2/Arsenic; EC 2.1.1.-/Methyltransferases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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