Author
Uthus, Eric |
Submitted to: International Society For Trace Elements Research In Humans
Publication Type: Abstract Only Publication Acceptance Date: 9/15/2001 Publication Date: 10/1/2001 Citation: Uthus, E.O. 2001. Arsenic essentiality: a role affecting methionine metabolism [abstract]. Journal of Trace Elements in Experimental Medicine. 14:368. Interpretive Summary: Technical Abstract: Although there is no known biological function of arsenic, circumstantial evidence indicates that arsenic has a physiological role related to methionine metabolism. In early studies using amino acid-based diets, it was found that arsenic deprivation had little effect on growth in rats fed adequate methionine. However, in rats fed deficient methionine, arsenic deprivation resulted in a significant reduction in body weight. Other studies showed that feeding methyl depletors caused signs of arsenic deprivation to be more severe. Because it was found that alteration in methionine status or methyl metabolism affected signs of arsenic deprivation and that many of these signs were related to methionine or methyl metabolism, it was hypothesized that arsenic has a physiological role affecting methionine metabolism. In animal studies testing this hypothesis, it was shown that arsenic deprivation reduces the hepatic concentration of S-adenosylmethionine(SAM) and increases the concentration of S-adenosylhomocysteine (SAH) resulting in a decreased SAM/SAH ratio. A decreased ratio of SAM/SAH is associated with DNA hypomethylation. Recent studies have shown that arsenic status can affect DNA methylation in animal and cell culture models; very low or high doses of arsenic, compared to control amounts, result in an apparent hypomethylation of DNA. Arsenic deprivation has also been shown to significantly alter the specific activity of betaine homocysteine methyltransferase depending on the folate status of the animal. Although many findings indicate that arsenic plays a role in methionine/methyl metabolism, the site of action of arsenic remains unknown. |