MOLECULAR CLONING OF PYRUVATE DEHYDROGENASE GENE

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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.