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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2018.tde-14032018-145930
Document
Author
Full name
Raíssa de Fátima Pimentel Melo
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Silber, Ariel Mariano (President)
Festuccia, William Tadeu Lara
Kowaltowski, Alícia Juliana
Muñiz, Bruno Dallagiovanna
Terra, Walter Ribeiro
Title in Portuguese
Caracterização molecular e funcional da imidazolona propionase de Trypanosoma cruzi: uma enzima do metabolismo de histidina.
Keywords in Portuguese
Trypansosoma cruzi
Histidina
Interação de proteínas
Metabolismo de aminoácidos
Reações metabólicas não enzimáticas
Abstract in Portuguese
O Trypanosoma cruzi é capaz de matabolizar aminoácidos como fontes de carbono e energia, dentre eles, o aminoácido histidina (His). Canonicamente, a via de degradação de His compreende quatro passos enzimáticos que consistem na oxidação de His a glutamato (Glu). O Glu gerado é convertido em alfa-cetoglutarato (α-KG), que é incorporado ao ciclo de Krebs (TCA), gerando coenzimas reduzidas que irão fornecer elétrons para a cadeia transportadora de elétrons (CTE), produzindo ATP. Nesse trabalho foi possível demonstrar que o substrato da terceira enzima envolvida na degradação de His (imidazolona propionase-TcIP), chamado 4-imidazolona-5-propionato (IPA) é oxidado não enzimáticamente a α-KG, e este é capaz de ser metabolizado diretamente via TCA. Ainda foi possível demonstrar que essa enzima se encontra formando um complexo macromolecular com a segunda enzima da via (urocanato hidratase TcUH). Finalmente, obervou-se que o controle da expressão da TcIP é importante no processo de metaciclogênse de T. cruzi.
Title in English
Molecular and functional characterization of imidazolonepropionase from Trypanosoma cruzi: an enzyme of histidine metabolism.
Keywords in English
Trypansosoma cruzi
Amino acids metabolism
Histidine
Non-enzymactic metabolic pathways
Proteins interaction
Abstract in English
Trypanosoma cruzi is able to catabolize amino acids as carbon and energy sources, among them the amino acid histidine (His). Canonically, the His degradation pathway comprises four enzymatic steps consisting of the oxidation of His to glutamate (Glu). The Glu is converted to alpha ketoglutarate (α-KG), which is incorporated into the Krebs cycle (TCA), generating reduced coenzymes that will supply electrons to the electron transport chain (ETC), producing ATP. In this work it was possible to demonstrate that the substrate of the third enzyme involved in the His degradation (imidazolonepropionase - TcIP), called 4-imidazolone-5-propionate (IPA), is non-enzymatically oxidized to α-KG, which is able to be metabolized directly through TCA. It was possible to demonstrate that this enzyme is forming a macromolecular complex with the second enzyme (urocanate hydratase - TcUH). Finally, it was established that the control of TcIP expression is important in the metacyclogenesis process in T. cruzi.
 
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Publishing Date
2018-03-14
 
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