title: Chloroquine resistance of Plasmodium berghei: biochemical basis and countermeasures.
abstract: Microsomal monooxygenases, enzymes that metabolize xenobiotics, may be responsible for the chloroquine resistance of malarial parasites. Plasmodium cells contain cytochrome P-450 and exhibit aryl hydrocarbon hydroxylase and aminopyrine N-dimethylase activity, two monooxygenases that inactivate chloroquine. The activities of these monooxygenases are considerably higher in chloroquine-resistant strains of Plasmodium berghei than in the chloroquine-sensitive strain of the parasite. Inhibitors of microsomal monooxygenases have the potential to overcome the chloroquine resistance of Plasmodium spp., and, of those inhibitors tested, the copper-lysine complex, copper(lysine)(2), was the most effective.
mesh_terms: D000633:Aminopyrine N-Demethylase / Q000378:metabolism*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D002738:Chloroquine / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology*; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008288:Malaria / Q000097:blood / Q000201:enzymology*; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; C053976:copper-lysine complex; D003300:Copper; D002738:Chloroquine; D001189:Aryl Hydrocarbon Hydroxylases; D000633:Aminopyrine N-Demethylase; D008239:Lysine