Research Article | Volume: 5, Issue: 10, October, 2015

Exploring novel drug targets in fatty acid pathway of Plasmodium falciparum

Meenakshi Pradhan I Arnold Emerson R Kiruba Thangam J Febin Prabhu Dass   

Open Access   

Published:  Oct 28, 2015

DOI: 10.7324/JAPS.2015.501018
Abstract

The malarial parasite Plasmodium falciparum infects humans and proliferates rapidly inside the host before its detection. The proliferation step requires a large amount of lipids for membrane synthesis. Thus fatty acid biosynthesis occurring in the apicoplast plays an important role in causing cerebral malaria. In this study, we explored and analyzed these pathways using stoichiometric matrix, elementary flux modes and robustness analysis. Based on the above analysis, the robustness of this pathway diminished as the result of virtual enzyme knock out indicating four key enzymes, 3-oxoacyl-ACP synthase, 3-oxoacyl-ACP synthase, 3-oxoacyl-ACP synthase and Glycerol-3-phosphate o-acyl transferase. Among the four, the first three are existing drug targets. Subsequently, we also found that a combinatorial double knock out of these enzymes predicts further reduction in overall pathway enzyme activity. Thus, we propose multi drug targeting as a better way to treat brain malaria.


Keyword:     Stoichiometric matrix Elementary Flux Modes Drug Target Malaria. Fatty Acid synthesis pathway.


Citation:

Meenakshi Pradhan, Arnold Emerson I, Kiruba Thangam R, Febin Prabhu Dass J. Exploring Novel Drug Targets in Fatty Acid Pathway of Plasmodium Falciparum. J App Pharm Sci, 2015; 5 (10): 107-112.

Copyright:The Author(s). This is an open access article distributed under the Creative Commons Attribution Non-Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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