This project concerns synthesis, content and function of polyamines in rodent passaged Trypanosoma brucei and a non-pathogenic insect Leptomonas. The levels of polyamines and their biosynthetic pathways are being studied using quantitative fluorometric analysis of trypanosome polyamine extracts, and radio tracer techniques for precursor detection. An important enzyme of trypanosomatid intermediatry metabolism, NAD-linked-alpha-glycerophosphate dehydrogenase, is being examined for polyamine activation and the effects of trypanocidal drugs on activity. A limited number of novel agents are being screened for activity in a T. brucei mouse system. These agents include established polyamine antagonists, antitumor agents, and drugs effective in other protozoan diseases. Another possible target for antitrypanosomatid drugs - heme -is being studied in collaboration with Dr. S. H. Hutner's group: Antiporphyrins and anti-hemes are being investigated for interference in the growth of insect trypanosomatids. This represents another conspicuous phyletic difference between Trypanosomatidae and vertebrates: Trypanosomatidae require exogenous porphyrin; vertebrates do not.