Inhibition by gossypol of oxidoreductases from Trypanosoma cruzi.
The effects of gossypol, a polyphenolic compound isolated from the cotton plant upon six oxidoreductases from cultured epimastigotes of Typanosoma cruzi were studied. Gossypol was a powerful inhibitor of the alpha-hydroxyacid and malate dehydrogenases, NAD-linked enzymes, and of glutamate dehydrogenase, malic enzyme and glucose-6-phosphate dehydrogenase, NADP-dependent enzymes. The drug did not have an effect on succinate dehydrogenase, a flavoprotein. The Ki values with respect to substrate were 0.73, 0.3 and 3.5 microM for alpha-hydroxyacid, malate and glutamate dehydrogenases, respectively, and 1.1, 0.19 and 7.8 microM with respect to the coenzyme. Inhibition was noncompetitive with respect to substrate and uncompetitive in relation to the coenzyme.
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D005969:Glutamate Dehydrogenase / Q000037:antagonists & inhibitors; D006072:Gossypol / Q000378:metabolism / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase; D045022:Lactate Dehydrogenases; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000201:enzymology*
D010088:Oxidoreductases; D000429:Alcohol Oxidoreductases; D045022:Lactate Dehydrogenases; D007770:L-Lactate Dehydrogenase; C071195:D-lactate dehydrogenase; D008291:Malate Dehydrogenase; C021379:D-2-hydroxyacid dehydrogenase; D005969:Glutamate Dehydrogenase; D006072:Gossypol