Branched chain alpha-ketoacid dehydrogenase and pyruvate dehydrogenase activity in isolated rat pancreatic islets.
Branched-chain alpha-ketoacid dehydrogenase and pyruvate dehydrogenase in isolated rat pancreatic islets were shown to be regulated by a phosphorylation/dephosphorylation mechanism. Broad-specificity phosphoprotein phosphatase treatment stimulated and ATP addition inhibited their activities. The kinases responsible for inactivating these complexes were shown to be sensitive to inhibition by known inhibitors, alpha-chloroisocaproate and dichloroacetate. Total activity (nmol/min/islet / 37 degrees C) of branched-chain alpha-ketoacid dehydrogenase and pyruvate dehydrogenase was 0.86 and 5.09, with a % active form (activity before phosphatase treatment divided by activity after phosphatase treatment X 100) of 36% and 94%, respectively. Incubation of intact isolated islets with alpha-chloroisocaproate affected neither insulin release nor flux through branched-chain alpha-ketoacid dehydrogenase.
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002208:Caproates / Q000494:pharmacology; D004789:Enzyme Activation; D006843:Hydrocarbons, Chlorinated; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology* / Q000378:metabolism; D007658:Ketone Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats
D002208:Caproates; D006843:Hydrocarbons, Chlorinated; D007328:Insulin; D009097:Multienzyme Complexes; D011768:Pyruvate Dehydrogenase Complex; C036533:2-chloroisocaproic acid; D000255:Adenosine Triphosphate; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D011494:Protein Kinases; C045455:phosphatase-1 kinase