Ornithine Decarboxylase in Trypanosoma brucei brucei: 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 T. brucei brucei [from rats]. 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 > 60-fold more sensitive to the inhibitor DL-.alpha.-difluoromethylornithine than its mammalian counterpart, thus making it an attractive target for chemotherapy.