MOLECULAR CLONING OF PYRUVATE DEHYDROGENASE GENE

我们实验室最近的研究表明，2，3-丁二醇， 在人类酒精血液中发现的两种不寻常的代谢物之一， 主要与患有酒精中毒的人类受试者相关 肝炎或酒精性肝硬化（Casazza等，酒精和 Alcoholism 1987;（suppl 1）：607-609）。 虽然确切的机制 2，3-丁二醇的形成是未知的，维奇和他的同事 假设它可以由丙酮酸盐产生 在脑和睾丸中发现的脱氢酶（Curr Top Cell Regulation 1981;18：151-179）。 根据提议，我们刚刚 开始了一个克隆丙酮酸基因的项目 使用合成的寡脱氧核苷酸探针的脱氢酶复合物。 通过核苷酸测序，我们已经证实我们的ElX克隆 EIB和E3代表真正的丙酮酸脱氢酶。 使用这些cDNA克隆，我们正在研究这些基因的调控。 尤其是在酗酒者身上。

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.