ENZYMOLOGY/MOLECULAR BIOLOGY OF ALDEHYDE DEHYDROGENASE

性状：（改编自研究者摘要）醛 解毒酶通常是去除有毒物质所必需的解毒酶。 细胞中的醛。 醛的范围从乙醛形成 在摄入的酒精饮料的氧化过程中， 光对多不饱和脂肪的作用。 最近发现， 一些用于化疗的药物形成细胞毒性醛， 缺乏酶的细胞，如一些肿瘤细胞和骨髓细胞。 酵母含有自己的乙醛脱氢酶，而HeLa细胞没有 酶 研究人员将从酵母中删除酶， 细胞可以用人类肝脏形式的酶转化并被 用来制造突变 这些将用于机械研究 并试图开发一种酶， 药物如环磷酰胺的毒性作用。 HeLa细胞将被 使它们能够代谢乙醇。 这些细胞将 用修饰的醛脱氢酶转化，因此它们可以用于 研究乙醛在突变酶存在下的代谢， 将生产。 许多东方人在消费时会有反应 酒精饮料. 这些人拥有一种改变了的，不活跃的 线粒体酶 然而，它们也拥有活性形式的拷贝 的酶。 将提出一种新的方法来生产这些 酶的异源四聚体，这样研究人员就可以研究一种失活的 亚基影响活性亚基的活性。 细胞也将 用于测定突变酶保护它们的体内能力。 一 将采用突变方法，以便研究人员可以研究 与酶的作用机制有关的问题， 能够设计醛脱氢酶的长期目标， 当用于基因替代疗法时具有更理想的性质，或 来制造转基因动物。

DESCRIPTION:(Adapted from the Investigator's Abstract) Aldehyde dehydrogenases are generally detoxifying enzymes necessary to remove toxic aldehydes from the cell. The aldehydes range from acetaldehyde formed during the oxidation of ingested alcoholic beverages, to some formed from the action of light on poly unsaturated fats. Recently it was found that some drugs used in chemotherapy form a cytotoxic aldehyde and will kill cells void of the enzymes, such as some tumor cells and bone marrow cells. Yeast contains its own aldehyde dehydrogenases while HeLa cells do not have the enzyme. The investigators will delete the enzyme from yeast so these cells can be transformed with the human liver forms of the enzyme and be used to make mutations in them. These will be used for mechanistic studies and to try to develop an enzyme more capable of protecting a cell against the toxic effects of drug such as cyclophophamides. HeLa cells will be changed so that they can metabolize ethanol. These cells will be transformed with modified aldehyde dehydrogenases so they can be used to study the metabolism of acetaldehyde in the presence of mutated enzymes they will produce. Many Oriental people suffer reactions when they consume alcoholic beverages. These people possess an altered, inactive form of the mitochondrial enzyme. However, they also possess copies of the active form of the enzyme. A new method will be proposed to produce these heterotetramers of the enzyme so the investigators can study how an inactive subunit affects the activity of the active subunit. The cells will also be used to determine in vivo ability of the mutated enzymes to protect them. A mutational approach will be employed so the investigators can study questions related to the mechanism of action of the enzyme, with the long term goal of being able to design aldehyde dehydrogenases which might possess more desirable properties when used in gene replacement therapy or to make transgenic animals.