Barry P. Rosen, Ph.D.
Florida International University
People with certain forms of the enzyme arsenic-3-methyltranferase (AS3MT) may retain arsenic longer in their bodies and may have an increased risk for arsenic-related diseases according to an NIEHS-funded study. The AS3MT enzyme metabolizes arsenic into a form that can be removed from the body. The structure of the enzyme can vary in humans.
The researchers identified eight variants of the human AS3MT enzyme, each of which contained single substitutions in amino acids, the building blocks of proteins. They characterized the properties of the variant enzymes and found that compared with AS3MT with no amino acid substitutions, the variants exhibited lower stability and decreased binding activity, which led to less efficient arsenic metabolism. The researchers predicted that individuals with these variants would have a higher proportion of monomethyl-arsenic, a more toxic arsenic metabolite linked to arsenic-related diseases. They also predicted that individuals with these variants would retain arsenic in their body for more time.
By determining the consequences of the single amino acid substitutions, the authors provided information about how the structure of the enzyme might be used to predict differences in arsenic metabolism. Understanding the variations in AS3MT might help explain why exposure to arsenic may lead to adverse health effects in some people and not in others.
Citation: Li J, Packianathan C, Rossman TG, Rosen BP. 2017. Nonsynonymous polymorphisms in the human AS3MT arsenic methylation gene: implications for arsenic toxicity. Chem Res Toxicol 30(7):1481–1491.