Pharmacogenetic and structural investigation of the Omega class glutathione transferases

Omega 类谷胱甘肽转移酶的药物遗传学和结构研究

• 批准号: nhmrc : 366731
• 负责人: A/Pr Aaron Oakley
• 金额: $ 32.67万
• 依托单位: Australian National University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/pharmacogenetic-structural-investigation-glutathione-transferases/94682
• 关键词: Pharmacogenetic; structural; investigation; Omega; class

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.

已知称为谷胱甘肽转移酶的酶家族的成员负责包括治疗药物和致癌化学物质在内的广泛化合物的代谢和解毒。个体谷胱甘肽转移酶的遗传变异可以改变他们对药物治疗的反应或对癌症的易感性。谷胱甘肽转移酶的欧米茄类是重要的，因为它们参与砷的代谢，因为它们已被证明会影响阿尔茨海默氏症和帕金森氏症的发病年龄。本研究将研究不同Omega类谷胱甘肽转移酶的结构和功能，并确定它们如何与含砷药物相互作用。这些研究将试图确定为什么砷的毒性在个体之间存在差异，并旨在预防癌症治疗中使用的含砷药物的不良反应。这些研究还将调查某些形式的欧米茄类谷胱甘肽转移酶的遗传可能影响阿尔茨海默病和帕金森病发病年龄的机制。对这一机制的理解可能为延迟或预防这些常见疾病的发作的治疗提供基础。