title: Inhibition by alloxan of mitochondrial aconitase and other enzymes associated with the citric acid cycle.
abstract: Considerable variations were found in the in vitro effect of alloxan on mouse liver enzymes associated with the citric acid cycle. The following approximative alloxan concentrations induced 50% inhibition of enzyme activity: 10(-6)M for aconitase, 10(-4)M for NAD-linked isocitrate dehydrogenase, glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinyl-CoA synthetase and fumarase, and 10(-3)M for citrate synthase and NADP-linked isocitrate dehydrogenase. Pyruvate dehydrogenase, succinate dehydrogenase and malate dehydrogenase were not inhibited by 10(-3)M alloxan. The inhibition of aconitase was competitive both when using mouse liver and purified porcine heart enzyme. The Ki values for the purified enzyme in the presence of 5 microM alloxan were 0.22 microM with citrate, 4.0 microM with cis-aconitate and 0.62 microM with isocitrate as substrate. The high sensitivity of aconitase for inhibition by alloxan probably plays a prominent role for the toxic effects of alloxan.
mesh_terms: D000154:Aconitate Hydratase / Q000037:antagonists & inhibitors*; D000496:Alloxan / Q000494:pharmacology*; D000818:Animals; D002950:Citrate (si)-Synthase / Q000037:antagonists & inhibitors; D002952:Citric Acid Cycle; D004305:Dose-Response Relationship, Drug; D005260:Female; D005969:Glutamate Dehydrogenase / Q000037:antagonists & inhibitors; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors; D007655:Ketoglutarate Dehydrogenase Complex / Q000037:antagonists & inhibitors; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D013389:Succinate-CoA Ligases / Q000037:antagonists & inhibitors
chemical_list: D000496:Alloxan; D008291:Malate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D007655:Ketoglutarate Dehydrogenase Complex; D005969:Glutamate Dehydrogenase; D002950:Citrate (si)-Synthase; D000154:Aconitate Hydratase; D013389:Succinate-CoA Ligases