Enzymatic differences between hycanthone-resistant and sensitive strains of Schistosoma mansoni.
1. Hycanthone-sensitive and resistant adult worms of Schistosoma mansoni were found to have generally similar specific activities in ten enzymes of carbohydrate metabolism. 2. Kinetic analyses revealed that pyruvate kinase, glucose-6-phosphate (G6P) dehydrogenase and malate dehydrogenase from both strains possessed similar Michaelis-Menten constants and were not inhibited by hycanthone. 3. Hexokinase and lactate dehydrogenase from the drug-resistant strain were not inhibited by hycanthone and showed three to five times greater Km values than those from the drug-sensitive worms which were also inhibitable by hycanthone. 4. Hycanthone more drastically affected the Vmax of phosphofructokinase from the hycanthone-sensitive parasite. 5. These data showed that the hycanthone inhibitable enzymes were generally from the drug-sensitive strain whereas the enzymes from drug-resistant worms are mostly hycanthone insensitive.
D000818:Animals; D004351:Drug Resistance; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006593:Hexokinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006826:Hycanthone / Q000494:pharmacology*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012550:Schistosoma mansoni / Q000187:drug effects / Q000201:enzymology*; D013892:Thioxanthenes / Q000494:pharmacology*
D013892:Thioxanthenes; D006826:Hycanthone; D007770:L-Lactate Dehydrogenase; D008291:Malate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D006593:Hexokinase; D010732:Phosphofructokinase-1; D011770:Pyruvate Kinase