alpha-Ketoacid dehydrogenase complexes and respiratory fuel utilisation in diabetes.
Activity of the pyruvate dehydrogenase complex determines the rate of glucose oxidation in animals including man. The complex is regulated by reversible phosphorylation, phosphorylation resulting in inactivation. Activity is therefore dependent upon the activities of pyruvate dehydrogenase kinase and phosphatase. Activity of the complex is reduced in diabetes and starvation as a result of insulin deficiency. The mechanism involves activation of pyruvate dehydrogenase kinase by short-term effects of products of fatty acid oxidation and by longer term effects involving specific protein synthesis; in hepatocytes the signals may include lipid fuels and glucagon. Activity of the branched chain ketoacid dehydrogenase complex determines the rate of degradation of branched chain aminoacids which is adjusted according to dietary supply. The complex is regulated by reversible phosphorylation, phosphorylation being inactivating. In liver and kidney, but not in muscles a protein activator (free E1 component) may reactivate phosphorylated complex without dephosphorylation and facilitate hepatic oxidation of branched chain ketoacids. Metabolic adjustments induced by diet and diabetes include loss of activator protein, loss of total complex activity in liver but not muscles, and enhanced inactivation by phosphorylation in liver.
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000818:Animals; D003920:Diabetes Mellitus / Q000201:enzymology / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D013217:Starvation / Q000378:metabolism
D009097:Multienzyme Complexes; D011768:Pyruvate Dehydrogenase Complex; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)