MOLECULAR CLONING OF PYRUVATE DEHYDROGENASE GENE

丙酮酸脱氢酶基因的分子克隆

• 批准号: 3817387
• 负责人: B J SONG
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3817387
• 关键词: alcoholic beverage consumption; alcoholic hepatitis; alcoholism /alcohol abuse; butanols; diol; genetic mapping; genetic markers; liver cirrhosis; liver metabolism; liver toxic disorder; molecular cloning; molecular pathology; nucleic acid probes; pyruvate dehydrogenase

Recent studies from our laboratory indicate that 2,3-butanediol, one of two unusual metabolites found in human alcoholic blood, is predominantly associated with human subjects who suffer alcoholic hepatitis or alcoholic cirrhosis (Casazza, et al., Alcohol and Alcoholism 1987;(suppl 1):607-609). Although the exact mechanism of 2,3-butanediol formation is not known, Veech and his associates have postulated that it could be generated by pyruvate dehydrogenase that are found in brain and testis (Curr Top Cell Regulation 1981;18:151-179). Based on the proposal, we have just started a project to clone genes encoding for pyruvate dehydrogenase complex using synthetic oligodexoynucleotide probes. By nucleotide sequencing, we have confirmed that our clones for ElX and EIB and E3 represent the authentic pyruvate dehydrogenase. Using these cDNA clones, we are studying the regulation of these genes especially in alcoholic subjects.

我们实验室的最新研究表明，2,3-丁二醇， 在人类酒精血液中发现的两个不寻常的代谢产物之一是 主要与遭受酗酒的人类受试者有关 肝炎或酒精性肝硬化（Casazza等人，酒精和酒精 酒精中毒1987;（增刊1）：607-609）。 虽然确切机制 Veech及其同事不知道2,3丁二醇的形成 假设它可以通过丙酮酸产生 在大脑和睾丸中发现的脱氢酶（Curr Top细胞 条例1981; 18：151-179）。 根据该提议，我们只有 开始了一个针对丙酮酸编码的基因的项目 脱氢酶复合物使用合成寡二氧核苷酸探针。 通过核苷酸测序，我们已经确认了我们的克隆 EIB和E3代表正宗丙酮酸脱氢酶。 使用这些cDNA克隆，我们正在研究这些克隆 基因，尤其是酒精受试者。