Relationship between activation state of pyruvate dehydrogenase complex and rate of pyruvate oxidation in isolated cerebro-cortical mitochondria: effects of potassium ions and adenine nucleotides.
The relation between the activation (phosphorylation) state of pyruvate dehydrogenase complex (PDHC; EC 1.2.4.1, EC 2.3.1.12, and EC 1.6.4.3) and the rate of pyruvate oxidation has been examined in isolated, metabolically active, and tightly coupled mitochondria from rat cerebral cortex. With pyruvate and malate as the substrates, the activation state of PDHC decreased on addition of ADP, while the rates of oxygen uptake and 14CO2 formation from [1-14C]pyruvate increased. The lack of correlation between the activation state of PDHC and rate of pyruvate oxidation was seen in media containing 5, 30, or 100 mM KCl. Both the activation state of PDHC and pyruvate oxidation increased, however, when KCl was increased from 5 to 100 mM. Although the PDHC is inactivated by an ATP-dependent kinase (EC 2.7.1.99), direct measurement of ATP and ADP failed to show a consistent relationship between the activation state of PDHC and either ATP levels or ATP/ADP ratios. Comparison of the activation state of PDHC in uncoupled or oligomycin-treated mitochondria also failed to correlate PDHC activation state to adenine nucleotides. In brain mitochondria, unlike those from other tissues, the activation state of PDHC does not seem to be related clearly to the rate of pyruvate oxidation, or to the mitochondrial adenylate energy charge.
D000123:Acetyltransferases / Q000378:metabolism; D000227:Adenine Nucleotides / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003653:Decarboxylation; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D004789:Enzyme Activation / Q000187:drug effects; D008293:Malates / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology*; D030481:Pyruvate Dehydrogenase (Lipoamide); D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D008293:Malates; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; D000244:Adenosine Diphosphate; C030298:malic acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D030481:Pyruvate Dehydrogenase (Lipoamide); D008058:Dihydrolipoamide Dehydrogenase; D000123:Acetyltransferases; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D011188:Potassium