Oxidative decarboxylation of 4-methylthio-2-oxobutyrate by branched-chain 2-oxo acid dehydrogenase complex.
Highly purified branched-chain 2-oxo acid dehydrogenase complex (BCOADC) oxidizes 4-methylthio-2-oxobutyrate and 2-oxobutyrate, with Km values of 67 microM and 18 microM respectively. The Vmax. for oxidation of these substrates is 27% and 53% respectively of that for 3-methyl-2-oxobutyrate. Highly purified pyruvate dehydrogenase complex (PDC) oxidizes 2-oxobutyrate (Km 100 microM; Vmax. 49% of that for pyruvate) but not 4-methylthio-2-oxobutyrate, whereas 2-oxoglutarate dehydrogenase complex will not utilize either 2-oxo acid as substrate. BCOADC kinase is inhibited by both 4-methylthio-2-oxobutyrate and 2-oxobutyrate, with half-maximal inhibition by 45 microM and 50 microM respectively. Phosphorylation of BCOADC in isolated adipocytes is inhibited by both 4-methylthio-2-oxobutyrate and 2-oxobutyrate, consistent with their inhibitory action of BCOADC kinase. Phosphorylation of PDC is decreased by 2-oxobutyrate, but not by 4-methylthio-2-oxobutyrate.
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000090:Acetoacetates / Q000494:pharmacology; D000273:Adipose Tissue / Q000201:enzymology; D003653:Decarboxylation; D066298:In Vitro Techniques; D007658:Ketone Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008715:Methionine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010084:Oxidation-Reduction; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism
D000090:Acetoacetates; D009097:Multienzyme Complexes; D011768:Pyruvate Dehydrogenase Complex; C016635:acetoacetic acid; C014632:2-keto-4-methylthiobutyric acid; D008715:Methionine; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)