Pharmacogenetic and structural investigation of the Omega class glutathione transferases

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Members of the family of enzymes known as glutathione transferases are known to be responsible for the metabolism and detoxification of a wide range of compounds including therapeutic drugs and cancer causing chemicals. Genetic variation in an individual's compliment of glutathione transferases can alter their response to drug treatment or their susceptibility to cancer. The Omega class of glutathione transferases are important because they are involved in the metabolism of arsenic and because they have been shown to influence the age-at-onset of both Alzheimer s and Parkinson s diseases. The present studies will investigate the structure and function of different Omega class glutathione transferases and determine how they interact with arsenic based drugs. These studies will attempt to determine why the toxicity of arsenic varies between individuals and aims to prevent adverse reactions to arsenic containing drugs used in cancer therapy. These studies will also investigate the mechanism by which the inheritance of certain forms of Omega class glutathione transferase can affect the age at-onset of Alzheimer s disease and Parkinson s disease. The understanding of this mechanism may provide the basis for a therapy that could delay or prevent the onset of these common diseases.