REGULATION OF BRANCHED-CHAIN AMINO-ACID CATABOLISM

Catabolism of the branched-chain amino acids is regulated in part at the step catalyzed by the branched-chain alpha-ketoacid dehydrogenase complex. Previous work suggests both short-term and long-term control mechanisms are involved in regulation of the kinase responsible for phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex. Recent work of this laboratory has focused on the isolation, characterization and molecular cloning of the branched-chain alpha-ketoacid dehydrogenase kinase, The cDNA obtained encodes the complete mature protein of 412 amino acids along with a mitochondrial entry sequence of 30 amino acids. Analysis of the deduced amino acid sequence revealed little similarity with eukaryotic Ser/Thr protein kinases. However, the kinase shows considerable sequence similarity with prokaryotic histidine protein kinases. The availability of this cDNA will facilitate gene expression studies of this important regulatory enzyme for the branched-chain alpha-ketoacid dehydrogenase complex.