Ornithine Decarboxylase in <i>Trypanosoma brucei brucei</i>: Evidence for Selective Toxicity of Difluoromethylornithine¹

Abstract

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.