Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity
Exposure to arsenic (As) through drinking water is a substantial problem worldwide. The methylation of As, a reactive metalloid, generates monomethyl- (MMA) and dimethyl-arsenical (DMA) species. The biochemical pathway that catalyzes these reactions, one-carbon metabolism, is regulated by folate and...
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Wiley
2012-01-01
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| Series: | Journal of Toxicology |
| Online Access: | http://dx.doi.org/10.1155/2012/595307 |
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| author | Megan N. Hall Mary V. Gamble |
| author_facet | Megan N. Hall Mary V. Gamble |
| author_sort | Megan N. Hall |
| collection | DOAJ |
| description | Exposure to arsenic (As) through drinking water is a substantial problem worldwide. The methylation of As, a reactive metalloid, generates monomethyl- (MMA) and dimethyl-arsenical (DMA) species. The biochemical pathway that catalyzes these reactions, one-carbon metabolism, is regulated by folate and other micronutrients. Arsenic methylation exerts a critical influence on both its urinary elimination and chemical reactivity. Mice having the As methyltransferase null genotype show reduced urinary As excretion, increased As retention, and severe systemic toxicity. The most toxic As metabolite in vitro is MMAIII, an intermediate in the generation of DMAV, a much less toxic metabolite. These findings have raised the question of whether As methylation is a detoxification or bioactivation pathway. Results of population-based studies suggest that complete methylation of inorganic As to DMA is associated with reduced risk for As-induced health outcomes, and that nutrients involved in one-carbon metabolism, such as folate, can facilitate As methylation and elimination. |
| format | Article |
| id | doaj-art-e7510a1972e84ebfa9fcb0bc8a8e56c1 |
| institution | OA Journals |
| issn | 1687-8191 1687-8205 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
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| series | Journal of Toxicology |
| spelling | doaj-art-e7510a1972e84ebfa9fcb0bc8a8e56c12025-08-20T02:21:09ZengWileyJournal of Toxicology1687-81911687-82052012-01-01201210.1155/2012/595307595307Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and ToxicityMegan N. Hall0Mary V. Gamble1Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 West 168th Street, Room T31, New York, NY 10032, USADepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 West 168th Street, Room 1107E, New York, NY 10032, USAExposure to arsenic (As) through drinking water is a substantial problem worldwide. The methylation of As, a reactive metalloid, generates monomethyl- (MMA) and dimethyl-arsenical (DMA) species. The biochemical pathway that catalyzes these reactions, one-carbon metabolism, is regulated by folate and other micronutrients. Arsenic methylation exerts a critical influence on both its urinary elimination and chemical reactivity. Mice having the As methyltransferase null genotype show reduced urinary As excretion, increased As retention, and severe systemic toxicity. The most toxic As metabolite in vitro is MMAIII, an intermediate in the generation of DMAV, a much less toxic metabolite. These findings have raised the question of whether As methylation is a detoxification or bioactivation pathway. Results of population-based studies suggest that complete methylation of inorganic As to DMA is associated with reduced risk for As-induced health outcomes, and that nutrients involved in one-carbon metabolism, such as folate, can facilitate As methylation and elimination.http://dx.doi.org/10.1155/2012/595307 |
| spellingShingle | Megan N. Hall Mary V. Gamble Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity Journal of Toxicology |
| title | Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity |
| title_full | Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity |
| title_fullStr | Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity |
| title_full_unstemmed | Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity |
| title_short | Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity |
| title_sort | nutritional manipulation of one carbon metabolism effects on arsenic methylation and toxicity |
| url | http://dx.doi.org/10.1155/2012/595307 |
| work_keys_str_mv | AT megannhall nutritionalmanipulationofonecarbonmetabolismeffectsonarsenicmethylationandtoxicity AT maryvgamble nutritionalmanipulationofonecarbonmetabolismeffectsonarsenicmethylationandtoxicity |