title: Mitochondrial 2-oxoacid dehydrogenase complexes of animal tissues.
abstract: The pyruvate dehydrogenase and branched-chain 2-oxoacid dehydrogenase complexes of animal mitochondria are inactivated by phosphorylation of serine residues, and reactivated by dephosphorylation. In addition, phosphorylated branched-chain complex is reactivated, apparently without dephosphorylation, by a protein or protein-associated factor present in liver and kidney mitochondria but not in heart or skeletal muscle mitochondria. Interconversion of the branched-chain complex may adjust the degradation of branched-chain amino acids in different tissues in response to supply. Phosphorylation is inhibited by branched-chain ketoacids, ADP and TPP. The pyruvate dehydrogenase complex is almost totally inactivated (99%) by starvation or diabetes, the kinase reactions being accelerated by products of fatty acid oxidation and by a protein or protein-associated factor induced by starvation or diabetes. There are three sites of phosphorylation, but only sites 1 and 2 are inactivating. Site 1 phosphorylation accounts for 98% of inactivation except during dephosphorylation when its contribution falls to 93%. Sites 2 and 3 are only fully phosphorylated when the complex is fully inactivated (starvation, diabetes). Phosphorylation of sites 2 and 3 inhibits reactivation by phosphatase. The phosphatase reaction is activated by Ca2+ (which may mediate effects of muscle work) and possibly by uncharacterized factors mediating insulin action in adipocytes.
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000818:Animals; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology*; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D012694:Serine / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; D011768:Pyruvate Dehydrogenase Complex; D012694:Serine; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D011494:Protein Kinases; D011770:Pyruvate Kinase; C035627:(3-methyl-2-oxobutanoate dehydrogenase (lipoamide)) kinase; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase