Arsenic Methylation and the S-Adenosyl Methionine Mediated
Transmethylation/Transulfuration Pathway
Joyce M. Donohue Ph.D., R.D., Charles O. Abernathy, Ph.D. US EPA, Washington DC.
Studies of arsenic and its methylated metabolites in human populations suggest that there is
considerable variability in the ability of individuals to methylate arsenic. One biochemical
pathway that may influence the degree of methylation is the S-adenosyl methionine
transmethylation/transulfuration pathway. This pathway is the site of a number of known genetic
defects influencing the fate of methionine and various intermediary metabolites. Although the
homozygous defects are fairly rare, little is known about the distribution of heterozygosity in the
population and its impact on transmethylation reactions. Other factors that influence the pathway
include the presence of competing substrates for methyl groups such as norepinephrine,
cobalamin, phosphatidyl ethanolamine, etc. The fate of intermediary metabolites such as
homocysteine, and the demand for, and dietary adequacy of the sulfur-containing amino acids
(methionine and cysteine) are other determinants that influence pathway function. The
physiological status of the B vitamins, folic acid, cobalamin and Vitamin B-6 can place
additional stress on the methylation efficacy of the pathway. Each of these variables are
considered from the perspective of their ability to influence the methlyation of arsenic either
directly or indirectly. [The opinions expressed in this abstract are those of the authors and not
necessarily those of USEPA.]
CORRESPONDING AUTHOR: Joyce M. Donohue, Ph.D., R.D. U.S. Environmental Protection
Agency, Mail Code 4304, Ariel Rios Building, 1200 Pennsylvania Avenue, NW, Washington,
DC 20460, USA.