Chlorothricin, and inhibitor of porcine-heart malate dehydrogenases, discriminating between the mitochondrial and cytoplasmic isoenzyme.
The macrolide-type antibiotic chlorothricin was found to inhibit both the mitochondrial and the cytoplasmic form of pig heart malate dehydrogenase. Steady-state kinetic measurements revealed that in the direction of oxalacetate reduction chlorothricin is competitive with respect to NADH and non-competitive with respect to oxalacetate. Both the variation of initial velocity with NADH concentration in the presence of antibiotic, and, at several fixed levels of NADH, the variation of initial velocity with chlorothricin concentration deviates from the classical Michaelis-Menten relationship for the two isoenzymes. Since, despite the very similar kinetic behaviour of the mitochondrial and cytoplasmic species of malate dehydrogenase, the concentration of chlorothricin required for half-maximal inhibition of the two enzymes differs by more than a factor of 10 (the mitochondrial isoenzyme being more susceptible to inhibition), it is concluded that the NADH binding sites of the mitochondrial and cytoplasmic form of malate dehydrogenase from pig heart are different.
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects / Q000201:enzymology; D006027:Glycosides / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors*; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D009243:NAD; D010084:Oxidation-Reduction; D013552:Swine
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D006027:Glycosides; D007527:Isoenzymes; D009243:NAD; D008291:Malate Dehydrogenase; C000451:chlorothricin