HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE AS A THERAPEUTIC TARGET IN PROTOZOAL INFECTIONS

The auxotrophy of parasitic protozoa for purines makes purine acquisit ion from the host a nutritional necessity for the survival and growth of these pathogens. The parasite hypoxanthine-guanine phosphoribosyltr ansferase (HGPRT) enzyme has been implicated as a critical enzyme in t his purine salvage process. Moreover, the HGPRT enzyme in some parasit es can also initiate the metabolism of purine base analogs that have l ittle effect on the mammalian host. This implies that either inhibitor s or substrates of HGPRT might serve as efficacious and selective agen ts for the treatment of parasitic diseases. This commentary provides a n overview of recent molecular and biochemical studies on HGPRT protei ns from parasitic protozoa and a discussion of the potential of HGPRT as a rational target for the chemotherapeutic manipulation of parasiti c diseases.