Full text
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| Author(s): |
Heloisa Berti Gabriel
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2011-02-11 |
| Examining board members: |
Alejandro Miguel Katzin;
Marie Anne van Sluys;
Silvia Reni Bortolin Uliana
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| Advisor: | Alejandro Miguel Katzin |
| Abstract | |
The lack of an effective vaccine and the problem of drug resistance haves hampered the control of malaria. The search for new biological targets for the development of effective antimalarials in part has focused on research and understanding of metabolic pathways unique to the parasite. Our group has investigated and characterized the products of the isoprenoids biosynthesis in P. falciparum. Preliminary results have identified the biosynthesis of two forms of vitamin K: phylloquinone (PhQ) and menaquinone (MQ), both derived from the Shikimate pathway and 2-C-methyl-D-erythritol-4-phosphate pathway (MEP). The shikimate and MEP pathways are unique to the parasite therefore are interesting targets for study and development of alternative drugs against the malaria. The enzimatic assay showed the participation of MQ-4 in the respiratory chain as electron carrier. Results indicated that the parasite controls the concentration of ubiquinone and menaquinone (UQ / MQ) according to the aeration conditions which is submitted, as described in E. coli and Ascaris suum. The MQ biosynthesis in P. falciparum is blocked by the compound Ro 48-8071, an inhibitor of the enzyme 1,4-dihydroxy-2-naftoato prenyltransferase. Also was described in the parasite, the biosynthesis of another form of vitamin K (PhQ) , and preliminary results showed probably participation of PhQ in the antioxidant protection in the cycle of P. falciparum. Finally, by the Real Time-PCR, we investigated the pattern of transcription of putative genes some enzymes of MQ, PhQ and UQ biosynthesis (the last was previously characterized). The results showed no changes in the transcription profile in the parasites kept in different conditions of O2 pressure. (AU) | |
| FAPESP's process: | 09/04152-4 - Assay of a possible biological funcion of carotenoids and vitamin K biosynthesized by intraerythrocytic forms of Plasmodium falciparum |
| Grantee: | Heloisa Berti Gabriel |
| Support Opportunities: | Scholarships in Brazil - Master |