Arsenic Methyltransferases

Enzymology of Arsenic Methylation 1. Characteristics of Arsenic Methyltransferases 

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Hayakawa, T Kobayashi, Y Cui, X. and Hirano, S. (2005) A new metabolic pathway of arsenite arsenic-glutathione complexes are substrates for human arsenic methyltransferase Cytl9. Archives of Toxicology, 79(4), 183-91. 

Waters, S.B., Devesa, V., Del Razo, L.M. et al. (2004a) Endogenous reductants support the catalytic function of recombinant rat Cytl9, an arsenic methyltransferase. Chemical Research in Toxicology, 17(3), 404-9. 

Figure 4.1 Sequence alignments for Homo sapiens (human), Rattus norvegicus (rat), and Mus musculus (mouse) arsenic (+3 oxidation state) methyltransferase (AS3MT). Positions of conserved nonnucleic acid sequence motifs (I, V, II, and III) indicated. Cysteinyl residues conserved in all three sequences marked with C. Accession numbers for sequences from NCBI GenBank H. sapiens (Q9HBK9) R. norvegicus (NP.5431 66) M. musculus (AAH13468).

Drobna, Z., Waters, S.B., Devesa, V. et al. (2005) Metabolism and toxicity of arsenic in human urothelial cells expressing rat arsenic (+3 oxidation state)-methyltransferase. Toxicology and Applied Pharmacology, 207(2), 147-59. 

Lin, S., Shi, Q., Brent Nix, F. et al. (2002) A novel S-adenosyl-L-methionine arsenic(HI) methyltransferase from rat liver cytosol. Journal of Biological Chemistry, 277(13), 10795-803. 

Wildfang, E., Zakharyan, R.A. and Aposhian, H.V. (1998) Enzymatic methylation of arsenic compounds VI. Characterization of hamster liver arsenite and methylarsonic acid methyltransferase activities in vitro. Toxicology and Applied Pharmacology, 152(2), 366-75. 

Zakharyan, R.A., Ayala-Fierro, F., Cullen, W.R. et al. (1999) Enzymatic methylation of arsenic compounds. VII. Monomethylarsonous acid (MMA(III)) is the substrate for MMA methyltransferase of rabbit liver and human hepatocytes. Toxicology and Applied Pharmacology, 158(1), 9-15. 

Zakharyan, R., Wu, Y., Bogdan, G.M. and Aposhian, H.V. (1995) Enzymatic methylation of arsenic compounds Assay, partial purification, and properties of arsenite methyltransferase and monomethylarsonic acid methyltransferase of rabbit liver. Chemical Research in Toxicology, 8(8), 1029-38. 

Studies of microbial systems have shown that the prodnc-tion of trimethylarsine from the various methylarsonates is more rapid than their respective thioarsinites, for example, Me2AsSR, MeAs(SR)2. However, there is a possible role for the thioarsinite in arsenic methylation. Studies on the binding of arsenic to the methyltransferase enzyme suggest that prior to the transfer of the methyl group the arsine oxide becomes bound to a thiolate at the active site. In this way it is possible to assist the binding of the softer arsenic substrate prior to... 

Methyl transferases AS3MT Arsenic (+3 oxidation state) methyltransferase 10q24.32... 

For example, arsenic exposure can lead to lung cancer, skin cancer, or non-cancerous effects to the skin. Arsenic is a naturally occurring element, and historically was used in insecticides. Absorbed arsenic will reach the liver. Once in the liver, the arsenic is converted to a nontoxic form by an enzyme, known as methyltransferase, and is then excreted from the body. 

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