A novel S-adenosyl-L-methionine:arsenic(III) methyltransferase from rat liver cytosol

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line, Transformed
  • Chromatography, Gel
  • Cytosol / enzymology*
  • DNA, Complementary
  • Humans
  • Kinetics
  • Liver / enzymology*
  • Male
  • Methyltransferases / chemistry
  • Methyltransferases / genetics
  • Methyltransferases / isolation & purification*
  • Methyltransferases / metabolism
  • Molecular Sequence Data
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred F344
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Substrate Specificity


  • DNA, Complementary
  • RNA, Messenger
  • Methyltransferases
  • S-adenosyl-L-methionine arsenic(III) methyltransferase

Associated data

  • GENBANK/AF393243