Ribokinase: A Possible Target for Chemotherapy of Protozoans

Abstract

The development of anti-parasitic agent is quite challenging particularly when exploiting biochemical differences between the parasite and the host. However, with post-genome bioinformatics and experimental research, drug targets can be more easily identified. Ribose metabolism in protozoans is of interest because protozoa in general are auxotrophic for purines and acquire these nutrients from the hosts1. Ribose is utilized in the production of ribose 5-phosphate required for the synthesis of 5-phosphoribosyl-1-pyrophosphate that is used with purine bases for the synthesis of nucleic acids. The enzyme responsible for the conversion of ribose to ribose 5-phosphate is ribokinase (an ATP-dependent phosphoribosyl kinase, EC 2.1.7.15). Four possible pathways exist for mobilization of free nucleobases for the synthesis of nucleic acids in protozoans, three of these use ribokinase and one uses transketolase / transaldolase pathway. Inhibition of these pathways, that is, the ribokinase pathway and transketolase / transaldolase pathway will deny the parasites ability to use the nucleobases to make nucleic acids.