Role of pyruvate transporter in the regulation of the pyruvate dehydrogenase multienzyme complex in perfused rat liver.
Metabolic substrates such as octanoate, beta-hydroxybutyrate, and alpha-ketoisocaproate which produce acetoacetate stimulate the rate of pyruvate decarboxylation in perfused livers from fed rats at perfusate pyruvate concentrations in the physiological range (below 0.2 mM). A quantitative relationship between pyruvate oxidation (14CO2 production from [1-14C]pyruvate) and ketogenesis (production of acetoacetate or total ketone bodies) was observed with all ketogenic substrates when studied over a wide range of concentrations. The ratio of extra pyruvate decarboxylated to extra acetoacetate produced was greater than 1 with octanoate and alpha-ketoisocaproate, but it was less than 1 with beta-hydroxybutyrate. The stimulatory effect of beta-hydroxybutyrate on pyruvate decarboxylation was abolished completely in the presence of 0.1 mM alpha-cyanocinnamate, an inhibitor of the pyruvate transporting system in the mitochondrial membrane. The data suggest that the mechanism by which the flux through the pyruvate dehydrogenase reaction is stimulated in liver under ketogenic conditions involves an acceleration of the net rate of pyruvate transport into the mitochondria compartment due to an exchange with acetoacetate and/or acetoacetate plus beta-hydroxybutyrate.
D000090:Acetoacetates / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D006885:Hydroxybutyrates / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D007651:Keto Acids / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism*; D051381:Rats
D000090:Acetoacetates; D006885:Hydroxybutyrates; D007651:Keto Acids; D007657:Ketone Bodies; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; C013082:alpha-ketoisocaproic acid