Ornithine decarboxylase in Trypanosoma brucei brucei: evidence for selective toxicity of difluoromethylornithine.
Activity of ornithine decarboxylase, the major rate limiting enzyme of polyamine biosynthesis, was determined in bloodstream trypomastigotes of Trypanosoma brucei brucei. The enzyme required pyridoxal-5'-phosphate, dithiothreitol and EDTA for optimal activity. Several properties of the enzyme were investigated and compared to the mammalian enzyme. Most notably, the parasite enzyme was greater than 60-fold more sensitive to the inhibitor DL-alpha-difluoromethylornithine than its mammalian counterpart, thus making it an attractive target for chemotherapy.
D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D000518:Eflornithine; D004790:Enzyme Induction; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008970:Molecular Weight; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000201:enzymology*
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; C025025:alpha-methylornithine; D009952:Ornithine; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; D000518:Eflornithine