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Master's Dissertation
DOI
10.11606/D.42.2011.tde-13022012-091618
Document
Author
Full name
Cristiana de Melo Trinconi
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Uliana, Silvia Reni Bortolin (President)
Heise, Norton
Winter, Carlos Eduardo
Title in Portuguese
Investigação sobre a atividade de Ceramida Sintase em Leishmania amazonensis.
Keywords in Portuguese
Leishmania
Ativação enzimática
Enzimas
Abstract in Portuguese
A leishmaniose é uma doença parasitária de ampla distribuição e de difícil tratamento. Recentemente foi identificada a atividade leishmanicida de tamoxifeno, levando à proposta de sua utilização como alternativa para o tratamento de leishmaniose. Neste trabalho, propusemo-nos a caracterizar a atividade de ceramida sintase (CerS) em L. amazonensis e testar a interferência do tamoxifeno nesta enzima. Identificamos, no genoma de L. amazonensis, uma ORF que codifica uma proteína similar à CerS de Saccharomyces cerevisiae, com seis domínios transmembrana e um motivo Lag1 característico. A caracterização da atividade enzimática in vitro mostrou que a enzima reconhece esfingosina/esfinganina e palmitoil/miristoil CoA como precursores. A enzima não é sensível à fumonisina B2 ou a tamoxifeno. Isto indica que esta droga não atua através da inibição da CerS. A caracterização completa desta enzima fornecerá dados valiosos sobre o metabolismo de esfingolipídeos nestes protozoários.
Title in English
Investigation of the Ceramide Synthase activity in Leishmania amazonensis.
Keywords in English
Leishmania
Enzyme activation
Enzymes
Abstract in English
Leishmaniasis is a widely distributed parasitic disease with difficult treatment. The leishmanicidal activity of tamoxifen was recently identified, leading to its proposal as an alternative treatment for leishmaniasis. In this work, we aimed at characterizing the activity of ceramide synthase (CerS) in L. amazonensis and testing whether this enzymatic activity in inhibited by tamoxifen. We have identified, in the L. amazonensis genome, an ORF which encodes a protein similar to the Saccharomyces cerevisiae CerS, with six transmembrane domains and a characteristic Lag1 motif. The characterization of the in vitro enzymatic activity showed that the enzyme recognizes sphingosine/sphinganine as well as palmitoyl/miristoyl CoA as precursors. This enzyme is not sensitive to fumonisin B2 or tamoxifen. This indicates that this drug does not act through the inibition of CerS. The complete characterization of this enzyme will provide valuable information about the sphingolipid methabolism of these protozoa.
 
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Publishing Date
2012-03-15
 
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