Malaria parasite metabolic pathway

The Malaria Parasite Metabolic Pathway (MPMP) is a website (http // sites.huji.ac.il/malaria last accessed 16 July 2008) that contains over 120 maps that encompasses not only classical biochemical pathways but next to each entry there is a 48-h clock that depicts stage-dependent transcription of a particular gene in P. falciparum. At the clock s zero hour, merozoites invade and at 12 o clock the 48-h cycle terminates. In the middle of the clock appears the hour of maximal transcript level. Clicking on the clock links to a transcriptomic database (http //malaria. ucsf.edu last accessed 16 July 2008). The enzymes are also linked to the International Union of Biochemistry and Molecular Biology website (http //www.iubmb.org last accessed 16 July 2008) where there is a detailed chemistry of the enzymatic reaction. Unlike other databases MPMP has been developed, curated and updated manually (Ginsburg, 2006). 

The malaria parasite, P. falciparum, obtains most of its requisite amino acids from the catabolism of host hemoglobin via a defined metabolic pathway which occurs in specialized digestive vacuoles at low pH (4.8-5.2). Ironically, one molecule of hemoglobin contains four molecules of... 

Shakespeare, P. G., Trigg, P. I., Kyd, S. I., and Tappenden, L. (1979a). Glucose metabolism in the simian malaria parasite Plasmodium knowlesi Activities of the glycolytic and pentose phosphate pathways during the intraerythrocytic cycle. Ann. Trap. Med. Parasitol. 73, 407-415. 

Fairlamb AH. Metabolic pathway analysis in trypanosomes and malaria parasites. Philos Trans R Soc Lond B Biol Sci 2002 357(l417) 101-7. 

Recently, we began the systematic study of purine metabolism of the IE form of the major human malaria pathogen, Plasmoditm falciparum, using newly developed techniques for continuous erythrocyte culture (1,2) and novel chromatographic procedures that permit comprehensive quantitative examination of purine intermediary pathways (3). Purines are essential to the rapidly proliferating malaria parasite for nucleic acid synthesis, energy metabolism and as enzyme cofactors (4). 

In this study we report on the metabolism of hypoxanthine by parasitized erythrocytes vitro. Emphasis was placed on identified differences in host and parasite purine pathways (5) and on how through use of specific inhibitors a rational approach to the selective destruction of the IE malaria parasite can be achieved. 

Over the last 20 years, the majority of Hyde and Sims studies have focused on folate biosynthesis in some way or another they have cloned and reported the sequence of all but one (DHNA) of the genes originally believed to make up the parasite s endogenous biosynthesis pathway, showed that the parasite can and does utilize exogenous (host-derived) folate thus posing additional questions about why and how anti-folates are successful in the treatment of malaria, and demonstrated the existence of a previously unrecognized gene likely to be involved in pterin metabolism that may provide an... 

Of the parasitic diseases the most devastating one is malaria with a worldwide death toll of more than a million people. It is transmitted by the mosquito. To combat this, the life cycle and metabolism of the parasite Plasmodium falciparum is affected through a reduction in the synthesis of xanthurenic acid (92). Xanthurenic acid, required for gametogenesis and fertility of the parasite, is synthesized in the tryptophan degradation pathway through the PLP-dependent enzyme kynurenine aminotransferase. Hence, this enzyme is a target for the development of antimalarial drugs. 

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