Malaria Parasite Pyrimidine Nucleotide Metabolism: A Promising Drug TargetJerapan Krungkrai*
Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Thailand
- *Corresponding Author:
- Jerapan Krungkrai
Department of Biochemistry, Faculty of Medicine, Chulalongkorn University
1873 Rama 4 Rd, Pathumwan, Bangkok 10330, Thailand
E-mail: [email protected]
Received date: January 13, 2017; Accepted date: May 02, 2017; Published date: May 05, 2017
Citation: Krungkrai J (2017) Malaria Parasite Pyrimidine Nucleotide Metabolism: A Promising Drug Target. Arch Parasitol 1:101.
Copyright: © 2017 Jerapan K. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Malaria is a major cause of morbidity and mortality in the tropical and subtropical endemic countries worldwide. This is largely due to the emergence and spread of resistance to most antimalarial drugs currently available, including the first-line treatment artemisinins. Thus, to fight this disease, there is an essential requirement to develop new antimalarial drugs for malaria chemotherapy. Plasmodium falciparum, the causative agent of the most lethal form of malaria in humans, cannot salvage preformed bases or nucleosides for pyrimidine synthesis and relies solely on pyrimidine nucleotides synthesized through the de novo biosynthetic pathway. In contrast, the human host cells have functionally operated both the salvage and de novo pathways. This mini review summarizes significant progress on understanding the pyrimidine nucleotide metabolism and the functional enzymes in the human parasite P. falciparum, which are different from the human host metabolic processes. Most recent information of the three-dimensional crystal structures and the catalytic mechanisms of the de novo pyrimidine enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors affecting these enzymatic activities are briefly reviewed in the context of their therapeutic potential against malaria.