A comparison of the enzymes of pathogenic protozoa to those of man is of fundamental importance to the search for much needed chemotherapeutic agents. The enzymes involved in purine salvage are of particular interest because most pathogenic protozoa lack the ability to synthesize purines de novo and consequently are obligate salvagers of preformed purines. This project involves a comparison of purine and pyrimidine metabolism of Trypanosoma and Leishmania. Comparisons of their biochemistry will be made within the parasitic group and to their host cells. Basic information regarding metabolic capacities of these organisms will be obtained. Attention will be given to the mechanisms by which these organisms absorb nutrients from their environment. These mechanisms involve enzymes excreted into their surroundings, enzymes located on the cell surface, and enzymes located within the cell. Enzyme and transport mechanisms which exhibit differences from those of host cells will offer targets for chemotherapeutic exploitation. Inhibitors will be sought which will affect these target systems. Those inhibitors which are trypanocides and/or leishmanicides will then be tested in an appropriate animal system. Extracellular and cell surface-associated enzymes which differ from those of the host will be tested for their potential for inducing immune control.