Longer-term regulation of branched-chain-2-oxoacid dehydrogenase complex studied in rat hepatocytes in culture.
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.
Beggs
M
M
Nuffield Department of Clinical Biochemistry, University of Oxford, U.K.
Shaw
J M
JM
Randle
P J
PJ
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000597:Amino Acids, Branched-Chain / Q000097:blood; D000818:Animals; D002478:Cells, Cultured; D004044:Dietary Proteins / Q000008:administration & dosage; D007651:Keto Acids / Q000097:blood; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats
D000597:Amino Acids, Branched-Chain; D004044:Dietary Proteins; D007651:Keto Acids; D009097:Multienzyme Complexes; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D011494:Protein Kinases; C035627:(3-methyl-2-oxobutanoate dehydrogenase (lipoamide)) kinase