The Human Arsenic Methylation Pathway Grant

abstract

  • The Environmental Protection Agency calls arsenic the most prevalent environmental toxin and carcinogen in the United States (://www.atsdr.cdc.gov/cercla/07list.html). Arsenic causes cardiovascular and peripheral vascular diseases, neurological disorders, diabetes mellitus and various forms of cancer such as skin and bladder cancer. Arsenic is biomethylated by the liver enzyme As (III) S-adenosylmethionine (SAM) methyltransferase (AS3MT) to mono- and dimethylated species. Because the trivalent products methylarsenite (MAs(III)) and dimethylarsenite (DMAs(III)) are more toxic than inorganic arsenite, they have been proposed to be associated with arsenic carcinogenesis and other diseases in humans. Individuals with AS3MT polymorphisms produce increased amounts of methylated species. How methylation contributes to disease depends on the mechanism of human AS3MT and differences between wild type and polymorphic enzymes. The uncertainty over the consequences of methylation makes it imperative to understand how this enzyme works. The overall goal of this study is elucidation of the structure and function of hAS3MT and its polymorphic forms.

date/time interval

  • December 11, 2014 - November 30, 2019

sponsor award ID

  • 1R01ES023779-01A1

local award ID

  • AWD000000004378

contributor

keywords

  • Affect
  • African American
  • American
  • Arsenic
  • Arsenites
  • Binding
  • Binding Sites
  • Biological Models
  • Cardiovascular system
  • Catalysis
  • Cells
  • Code
  • Cysteine
  • Data
  • Diabetes Mellitus
  • Disease
  • Environmental Carcinogens
  • Enzymes
  • European
  • Genes
  • Genetic Polymorphism
  • Genome
  • Glutathione S-Transferase
  • Goals
  • Human
  • Human Genome
  • In Vitro
  • Individual
  • Kinetics
  • Lead
  • Life
  • Liver
  • Malignant Neoplasms
  • Malignant neoplasm of urinary bladder
  • Metabolic Clearance Rate
  • Methylation
  • Methyltransferase
  • Missense Mutation
  • Modeling
  • Mono-S
  • Mutation
  • National Heart, Lung, and Blood Institute
  • Nature
  • Pathway interactions
  • Peripheral Vascular Diseases
  • Physiological
  • Production
  • Property
  • Reaction
  • Reduced Glutathione
  • Reducing Agents
  • Risk
  • Role
  • S-Adenosylmethionine
  • Scheme
  • Skin Cancer
  • Solutions
  • Structure
  • Subarachnoid Hemorrhage
  • Sum
  • Thioredoxin
  • Toxic Environmental Substances
  • Uncertainty
  • United States
  • United States Environmental Protection Agency
  • Variant
  • Work
  • carcinogenesis
  • disulfide bond
  • exome sequencing
  • glutathione S-transferase pi
  • in vivo
  • nervous system disorder
  • oxidation
  • public health relevance
  • repository
  • screening
  • thioredoxin reductase