Lin Shan, Shi Qing, Nix F Brent, Styblo Miroslav, Beck Melinda A, Herbin-Davis Karen M, Hall Larry L, Simeonsson Josef B, Thomas David J
Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
J Biol Chem. 2002 Mar 29;277(13):10795-803. doi: 10.1074/jbc.M110246200. Epub 2002 Jan 14.
S-Adenosyl-l-methionine (AdoMet):arsenic(III) methyltransferase, purified from liver cytosol of adult male Fischer 344 rats, catalyzes transfer of a methyl group from AdoMet to trivalent arsenicals producing methylated and dimethylated arsenicals. The kinetics of production of methylated arsenicals in reaction mixtures containing enzyme, AdoMet, dithiothreitol, glutathione (GSH), and arsenite are consistent with a scheme in which monomethylated arsenical produced from arsenite is the substrate for a second methylation reaction that yields dimethylated arsenical. The mRNA for this protein predicts a 369-amino acid residue protein (molecular mass 41056) that contains common methyltransferase sequence motifs. Its sequence is similar to Cyt19, a putative methyltransferase, expressed in human and mouse tissues. Reverse transcription-polymerase chain reaction detects S-adenosyl-l-methionine:arsenic(III) methyltransferase mRNA in rat tissues and in HepG2 cells, a human cell line that methylates arsenite and methylarsonous acid. S-Adenosyl-l-methionine:arsenic(III) methyltransferase mRNA is not detected in UROtsa cells, an immortalized human urothelial cell line that does not methylate arsenite. Because methylation of arsenic is a critical feature of its metabolism, characterization of this enzyme will improve our understanding of this metalloid's metabolism and its actions as a toxin and a carcinogen.
S-腺苷-L-甲硫氨酸（AdoMet）：砷（III）甲基转移酶，从成年雄性Fischer 344大鼠的肝脏胞质溶胶中纯化得到，催化将AdoMet上的甲基转移至三价砷化合物，生成甲基化和二甲基化的砷化合物。在含有酶、AdoMet、二硫苏糖醇、谷胱甘肽（GSH）和亚砷酸盐的反应混合物中，甲基化砷化合物的生成动力学符合一种机制，即由亚砷酸盐产生的单甲基化砷化合物是第二个甲基化反应的底物，该反应产生二甲基化砷化合物。该蛋白质的mRNA预测有一个369个氨基酸残基的蛋白质（分子量41056），其包含常见的甲基转移酶序列基序。它的序列与在人和小鼠组织中表达的一种假定的甲基转移酶Cyt19相似。逆转录-聚合酶链反应在大鼠组织和HepG2细胞（一种能使亚砷酸盐和甲基亚砷酸甲基化的人细胞系）中检测到S-腺苷-L-甲硫氨酸：砷（III）甲基转移酶mRNA。在UROtsa细胞（一种永生化的人尿道上皮细胞系，不能使亚砷酸盐甲基化）中未检测到S-腺苷-L-甲硫氨酸：砷（III）甲基转移酶mRNA。由于砷的甲基化是其代谢的关键特征，对这种酶的表征将增进我们对这种类金属代谢及其作为毒素和致癌物作用的理解。
