Inhibition of glutamate dehydrogenase and malate dehydrogenases by palmitoyl coenzyme A.
In extension of a previous study with yeast glucose-6-P dehydrogenase (Kawaguchi, A., and Bloch, K. (1974) J. Biol. Chem. 249, 5793-5800), the structural changes accompanying the inhibition of glutamate dehydrogenase and several malate dehydrogenases by palmitoyl-CoA and by sodium dodecyl sulfate have been investigated. Palmitoyl-CoA converts liver glutamate dehydrogenase to enzymatically inactive dimeric subunits (Mr = 1.2 X 10(5)) and tightly binds to the dissociated enzyme. Removal of the inhibitor from the palmitoyl-CoA-dimer complex fails to regenerate enzyme activity. The Ki values for palmitoyl-CoA inhibition of malate dehydrogenases (oxalacetate reduction) are, for the enzyme from pig heart mitochondria, 1.8 muM, 500 muM from pig heart supernatant, and 10 muM from chicken heart supernatant. These inhibitions are readily reversible. Palmitoyl-CoA does not alter the quaternary structure of any of the malate dehydrogenases and binds only weakly to these enzymes. Mitochondrial malate dehydrogenase assayed in the direction malate to oxalacetate is much less sensitive to palmitoyl-CoA, with Ki values of 50 muM at pH 10 and greater than 50 muM at pH 7.4. While the differences in palmitoyl-CoA sensitivity in the forward and backward reactions catalyzed by mitochondrial dehydrogenase are unexplained, a physiological rationale for these differential effects is offered. Sodium dodecyl sulfate dissociates the various dehydrogenases to monomeric subunits in contrast to the more selective effects of palmitoyl-CoA.
D000818:Animals; D002417:Cattle; D002645:Chickens; D003065:Coenzyme A / Q000494:pharmacology*; D003593:Cytoplasm / Q000201:enzymology; D005227:Fatty Acids / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008931:Mitochondria, Muscle / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D010169:Palmitic Acids / Q000494:pharmacology; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013552:Swine
D005227:Fatty Acids; D010169:Palmitic Acids; D012967:Sodium Dodecyl Sulfate; D003065:Coenzyme A