Longer-term regulation of branched-chain-2-oxoacid dehydrogenase complex studied in rat hepatocytes in culture. 1989

M Beggs, and J M Shaw, and P J Randle
Nuffield Department of Clinical Biochemistry, University of Oxford, U.K.

The effect of protein-free diet to decrease liver activity of branched-chain (-2-oxoacid) dehydrogenase (BCD) complex (active form) and increase BCD kinase activity was unaffected by preparation of hepatocytes, but partially reversed by 25 h of culture of hepatocytes in medium 199. Activation of BCD complex preceded loss of BCD kinase. The effect of culture on BCD complex was completely prevented by omission of branched-chain amino acids and partially prevented by 1 mM-alpha-cyano-4-hydroxycinnamate or 0.2 mM-pyruvate/2 mM-lactate. Protein-free diet decreased plasma branched-chain amino and oxo ('keto') acids and increased plasma pyruvate and lactate. It is concluded: (1) that branched-chain amino acids are involved directly in regulation of activities of BCD complex and BCD kinase; (2) that mitochondrial uptake of branched-chain oxo acids is necessary for regulation of BCD complex activity; and (3) that the stable increase in BCD kinase may function as a hysteresis mechanism.

UI MeSH Term Description Entries
D007651 Keto Acids Carboxylic acids that contain a KETONE group. Oxo Acids,Oxoacids,Acids, Keto,Acids, Oxo
D007658 Ketone Oxidoreductases Oxidoreductases that are specific for KETONES. Oxidoreductases, Ketone
D008930 Mitochondria, Liver Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4) Liver Mitochondria,Liver Mitochondrion,Mitochondrion, Liver
D009097 Multienzyme Complexes Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES. Complexes, Multienzyme
D011494 Protein Kinases A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. Protein Kinase,Kinase, Protein,Kinases, Protein
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004044 Dietary Proteins Proteins obtained from foods. They are the main source of the ESSENTIAL AMINO ACIDS. Proteins, Dietary,Dietary Protein,Protein, Dietary
D000597 Amino Acids, Branched-Chain Amino acids which have a branched carbon chain. Branched-Chain Amino Acid,Amino Acids, Branched Chain,Acid, Branched-Chain Amino,Acids, Branched-Chain Amino,Amino Acid, Branched-Chain,Branched Chain Amino Acid,Branched-Chain Amino Acids
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D042942 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) A ketone oxidoreductase that catalyzes the overall conversion of alpha-keto acids to ACYL-CoA and CO2. The enzyme requires THIAMINE DIPHOSPHATE as a cofactor. Defects in genes that code for subunits of the enzyme are a cause of MAPLE SYRUP URINE DISEASE. The enzyme was formerly classified as EC 1.2.4.3. 2-Oxoisovalerate Dehydrogenase (Lipoamide),2-Oxoisocaproate Dehydrogenase,Alpha-Keto Acid Dehydrogenase,BCKA Decarboxylase,Branched Chain Alpha-Keto Acid Decarboxylase,Branched Chain Ketoacid Dehydrogenase,Branched-Chain 2-Oxo Acid Dehydrogenase,Branched-Chain Keto Acid Dehydrogenase,Branched-Chain Oxo-Acid Dehydrogenase,2 Oxoisocaproate Dehydrogenase,Acid Dehydrogenase, Alpha-Keto,Alpha Keto Acid Dehydrogenase,Branched Chain 2 Oxo Acid Dehydrogenase,Branched Chain Alpha Keto Acid Decarboxylase,Branched Chain Keto Acid Dehydrogenase,Branched Chain Oxo Acid Dehydrogenase,Decarboxylase, BCKA,Dehydrogenase, 2-Oxoisocaproate,Dehydrogenase, Alpha-Keto Acid,Dehydrogenase, Branched-Chain Oxo-Acid,Oxo-Acid Dehydrogenase, Branched-Chain

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