Leishmania mexicana: enzyme activities of amastigotes and promastigotes and their inhibition by antimonials and arsenicals.
A major difference between the metabolism of Leishmania species amastigotes and cultured promastigotes was found in the area of CO2 fixation and phosphoenolpyruvate metabolism. Malate dehydrogenase (EC 1.1.1.37) and phosphoenolpyruvate carboxykinase (EC 4.1.1.49) were at much higher activities in amastigotes than promastigotes of both L. m. mexicana and L. donovani, whereas the reverse was true of pyruvate kinase (EC 2.7.1.40). Pyruvate carboxylase (EC 6.4.1.1) and malic enzyme (carboxylating) (EC 1.1.1.40) could not be detected in L. m. mexicana amastigotes. Promastigotes of L. m. mexicana had a high NAD-linked glutamate dehydrogenase activity in comparison to amastigotes, whereas NADP-linked glutamate dehydrogenase activity was detected only in amastigotes. Leishmania m. mexicana culture promastigotes were killed in vitro by the trivalent antimonial Triostam (LD50, 20 micrograms/ml) and the trivalent arsenical melarsen oxide (LD50, 20 micrograms/ml), but they were unaffected by Pentostam. Neither antimonial drug significantly inhibited leishmanial hexokinase (EC 2.7.1.2), phosphofructokinase (EC 2.7.1.11), pyruvate kinase, malate dehydrogenase or phosphoenolpyruvate carboxykinase, whereas melarsen oxide was a potent inhibitor of all the enzymes tested except phosphoenolpyruvate carboxykinase.
Mottram
J C
JC
Coombs
G H
GH
D000818:Animals; D000965:Antimony / Q000494:pharmacology; D000967:Antimony Sodium Gluconate / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001152:Arsenicals / Q000494:pharmacology*; D002952:Citric Acid Cycle; D005942:Gluconates / Q000494:pharmacology*; D006019:Glycolysis; D006593:Hexokinase / Q000037:antagonists & inhibitors; D007891:Leishmania / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors; D008549:Melarsoprol / Q000494:pharmacology; D009942:Organometallic Compounds; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000037:antagonists & inhibitors; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors; D014227:Triazines / Q000494:pharmacology
D000981:Antiprotozoal Agents; D001152:Arsenicals; D005942:Gluconates; D009942:Organometallic Compounds; D014227:Triazines; C044719:melarsen oxide; C008345:melarsen; C044720:M&B 1714; D000965:Antimony; D008291:Malate Dehydrogenase; D006593:Hexokinase; D010732:Phosphofructokinase-1; D011770:Pyruvate Kinase; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D000967:Antimony Sodium Gluconate; D008549:Melarsoprol