Hypoxanthine-guanine phosphoribosyltransferase as a therapeutic target in protozoal infections

The auxotrophy of parasitic protozoa for purines makes purine acquisition from the host a nutritional necessity for the survival and growth of these pathogens. The parasite hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme has been implicated as a critical enzyme in this purine salvage process. Moreover, the HGPRT enzyme in some parasites can also initiate the metabolism of purine base analogs that have little effect on the mammalian host. This implies that either inhibitors or substrates of HGPRT might serve as efficacious and selective agents for the treatment of parasitic diseases. This commentary provides an overview of recent molecular and biochemical studies on HGPRT proteins from parasitic protozoa and a discussion of the potential of HGPRT as a rational target for the chemotherapeutic manipulation of parasitic diseases.