ENZYMOLOGY/MOLECULAR BIOLOGY OF ALDEHYDE DEHYDROGENASE

描述：(改编自《调查者摘要》)乙醛 脱氢酶通常是清除有毒物质所必需的解毒酶。 细胞中的醛。醛的范围从乙醛到乙醛 在饮用酒精饮料的氧化过程中，会形成一些由 光对多不饱和脂肪的作用。最近发现， 化疗中使用的一些药物会形成一种细胞毒性醛，并会杀死 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 这种酶。研究人员将从酵母中删除这种酶，因此这些 细胞可以转化为人类肝脏形式的酶，并被 用来使它们发生突变。这些将用于机械学研究。 并试图开发一种更能保护细胞免受感染的酶 环磷酰胺等药物的毒性作用。HeLa细胞将是 这样它们就可以代谢乙醇。这些细胞将是 用改良的乙醛脱氢酶转化，这样它们就可以用来 乙醛在突变酶存在下的代谢研究 将会产生。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的、不活跃的形式的 线粒体酶。然而，他们也拥有活动形式的副本 酶的活性。将提出一种新的方法来生产这些产品 酶的异构体，这样研究人员就可以研究一种不活跃的 亚基影响活性亚基的活性。这些牢房也将是 用于在体内测定突变酶保护它们的能力。一个 将采用突变方法，以便调查人员能够研究 与酶的作用机制有关的问题，随着时间的推移 能够设计乙醛脱氢酶的学期目标可能 在基因替代疗法中使用时具有更理想的特性 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.