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Doctoral Thesis
DOI
10.11606/T.42.2015.tde-23122015-084842
Document
Author
Full name
Rodrigo Antonio Ceschini Sussmann
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Katzin, Alejandro Miguel (President)
Bargieri, Daniel Youssef
Hotta, Carlos Takeshi
Miguel, Danilo Ciccone
Miyamoto, Sayuri
Title in Portuguese
Estudo da função de vitamina E e da biossíntese de vitamina K1 em Plasmodium falciparum.
Keywords in Portuguese
Plasmodium falciparum
Antimaláricos
Malária
Sistema redox
Vitamina E
Vitamina K1
Abstract in Portuguese
A malária apresenta um alto índice de mortalidade com mais de 500 mil mortes registradas em 2013. Para agravar a situação de saúde pública, foi descrito o surgimento de resistência às drogas usadas na terapêutica da doença. Torna-se necessário a identificação e o estudo de novos alvos antimaláricos. A via MEP se mostra como um potencial alvo para o desenvolvimento de drogas contra P. falciparum uma vez que está ausente em humanos. Nossos objetivos foram avaliar a função da vitamina E biossintetizada pelo parasita, caracterizar a biossíntese de vitamina K1 e o metabolismo de fitol. Esse estudo determinou que a vitamina E biossintetizada pelo parasita atua no sistema redox do parasita. Por outro lado, mostramos que a biossíntese de vitamina K1 é ativa no parasita e detectamos sua forma reduzida. Por fim, observamos que existe uma via de reaproveitamento de fitol em P. falciparum assim como em plantas. O estudo abre oportunidades para um desenvolvimento racional de novos antimaláricos e aprofunda o conhecimento na biologia do parasita.
Title in English
Estudy of vitamin E function and of vitamin K1 biosynthesis in Plasmodium falciparum.
Keywords in English
Plasmodium falciparum
Antimalarials
Malaria
Redox system
Vitamin E
Vitamin K1
Abstract in English
Malaria has the highest mortality rate with more than 500 000 deaths in 2013. The public health situation gets worse because it has been described the emergence of resistance to common drugs used in the treatment of disease. It is necessary to identify and study of new antimalarial targets. The MEP pathway is a potential target for drug development against Plasmodium falciparum once it is absent in humans. Our objectives were to evaluate the function of vitamin E biosynthesized by the parasite and characterize the biosynthesis of vitamin K1 and the phytol metabolism. This study determined that vitamin E biosynthesized by the parasite operates in the redox system of the parasite. We show the biosynthesis of vitamin K1 is active on parasite and we detected its reduced form. Finally, we demonstrate that there is a phytol salvage pathway in P. falciparum as well as plants. The study opens opportunities for the rational development of new antimalarials and deepens knowledge on parasite biology.
 
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Release Date
2017-12-22
Publishing Date
2015-12-23
 
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