Methylerythritol phosphate pathway to isoprenoids: Kinetic modeling andin silicoenzyme inhibitions inPlasmodium falciparum

• DOI: 10.1016/j.febslet.2013.06.024
• Publication Date: 2013-06-29T01:02:00Z
• Authors: Vivek Kumar Singh; Indira Ghosh
• Keywords: Metabolic pathway

The methylerythritol phosphate (MEP) pathway of Plasmodium falciparum (P. falciparum) has become an attractive target for anti-malarial drug discovery. This study describes a kinetic model this pathway, its use in validating 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) as from the systemic perspective, and additional identification, using metabolic control analysis silico inhibition studies. In addition to DXR, synthase (DXS) can be targeted because it is first enzyme highest flux coefficient followed by that DXR. both enzymes caused large decrement flux. An added advantage targeting DXS influence on vitamin B1 B6 biosynthesis. Two more potential targets, 2-C-methyl-d-erythritol 2,4-cyclodiphosphate 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase, were also identified. Their accumulation their substrates causing instability system. demonstrates types one acting via reduction other metabolite accumulation, exist P. MEP pathway. These groups targets exploited independent drugs.