Research Advances in Purine Phosphoribosyltransferases of Protozoan Parasites

Abstract

Parasitic protozoa are single-celled organisms that have adapted to live in cells of humans and animals. The protozoan parasites include Leishmania spp., Trypanosoma spp., Plasmodium spp., Toxoplasma gondii, Cryptosporidium spp., and Eimeria spp., which can cause protozoal diseases that seriously endanger human and animal health and cause huge economic losses in the livestock industry. Parasite development and reproduction after invasion of the host require a large number of purine nucleotides, and the corresponding purine bases are catalyzed by purine phosphoribosyl transferase to generate the corresponding purine nucleotides. Purine phosphoribosyltransferases (PPRT) are important metabolic enzymes involved in the ribophosphorylation of purine bases and are present in many protozoan parasites. Adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) belong to PPRT. APRT and HGXPRT convert adenine, hypoxanthine, guanine, and xanthine into adenosine-5'-monophosphate (AMP), inosine-5 '-monophosphate (IMP), guanosine-5'-monophosphate (GMP), and xanthosine- 5'-monophosphate (XMP), respectively. Purine nucleotides are involved in many functions as components of DNA and RNA, as enzyme cofactors in metabolic pathways, as sources of energy in protozoan parasites. Purine phosphoribosyltransferases are key enzyme in the purine salvage pathway of parasitic protozoa, which is significantly different from the de novo synthesis pathway of the host. In recent years, purine phosphoribosyltransferases have become the interesting research hotspot as an antiparasitic drug candidates target, with major progress in the screening of compounds against protozoan parasites. This review focuses on the basic characteristics, biological functions, inhibitors screening and application of purine phosphoribosyltransferases in parasitic protozoa of Leishmania spp., Trypanosoma spp., Plasmodium spp., and Toxoplasma gondii, so as to provide reference for the research of drug targets and the screening of new inhibitors against parasitic protozoa.

Keywords

• protozoan parasites
• adenine phosphoribosyltransferase
• hypoxanthine-guanine-xanthine phosphoribosyltransferase
• purine nucleotide
• drug target
• inhibitors