Dihydrofolate reductase from Eimeria tenella: rationalization of chemotherapeutic efficacy of pyrimethamine.
Dihydrofolate reductase activity of 0.2 nmole of dihydrofolate reduced/min/mg protein was detected in crude extracts of unsporulated oocysts of Eimeria tenella. The enzyme was purified by a combination of affinity and ion-exchange chromatography. Its molecular weight was estimated as 240,000 daltons. An anticoccidial drug pyrimethamine is a potent inhibitor of the activity of E. tenella dihydrofolate reductase (Ki = 3 nM), but it is less effective an inhibitor of dihydrofolate reductase from chicken liver. This difference may explain the in vivo therapeutic action of pyrimethamine against Coccidia.
D000818:Animals; D002645:Chickens; D004539:Eimeria / Q000201:enzymology*; D005493:Folic Acid Antagonists; D008099:Liver / Q000201:enzymology; D008727:Methotrexate / Q000494:pharmacology; D008970:Molecular Weight; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000302:isolation & purification / Q000378:metabolism*
D005493:Folic Acid Antagonists; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate; D011739:Pyrimethamine