title: Regulation of oxidative decarboxylation of branched-chain 2-oxo acids in rat liver mitochondria.
abstract: At 0.1 mM 2-oxo[1-14C]isocaproate or 2-oxo[1-14C]isovalerate plots of the reciprocal of the rate of 14CO2 formation by branched-chain 2-oxo acid dehydrogenase complex in mitochondria vs alpha-cyanocinamate concentration were linear up to high inhibitor concentrations, indicating that the monocarboxylate carrier-mediated transport was the rate-limiting step. At low (0.025 mM) concentration of 2-oxo[1-14C]isocaproate or 2-oxo[1-14C]isovalerate the 1/v vs I plots became nonlinear indicating that the branched-chain 2-oxo acid dehydrogenase activity determined the rate of 14CO2 formation. Inhibition of branched-chain 2-oxo acid dehydrogenase complex by clofibric acid or arsenite showed that at 0.1 mM 2-oxoisovalerate the activity of the complex became the rate-limiting step of the pathway. The availability of the 2-oxoisocaproate or 2-oxoisovalerate seems to affect the phosphorylation and the activity of the branched-chain 2-oxo acid dehydrogenase complex only at low, physiological concentrations of these substrates (less than 0.025 mM).
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000818:Animals; D002250:Carbon Radioisotopes; D002934:Cinnamates / Q000494:pharmacology; D006706:Homeostasis; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology*; D027501:Monocarboxylic Acid Transporters; D009097:Multienzyme Complexes / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002250:Carbon Radioisotopes; D002934:Cinnamates; D027501:Monocarboxylic Acid Transporters; D009097:Multienzyme Complexes; C018253:alpha-cyanocinnamate; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)