El NAD+ en parásitos extracelulares: Procesos biosintéticos y de transporte

dc.contributor.advisorRamirez Hernandez, Maria Helena
dc.contributor.authorVillalobos Gonzalez, Leidy Constanza
dc.contributor.researchgroupLibbiq Unspa
dc.date.accessioned2022-08-24T16:58:56Z
dc.date.available2022-08-24T16:58:56Z
dc.date.issued2021
dc.descriptionilustraciones, fotografías, graficasspa
dc.description.abstractEl Dinucleótido de nicotinamida y adenina (NAD+/NADH) es una de las principales coenzimas en numerosos procesos de óxido-reducción celular, la cual se encuentra adicionalmente involucrada en la reparación del ADN, señalización celular, apoptosis, entre otras. La formación del NAD+ se da a partir del Mononucleótido de Nicotinamida (NMN) o el Mononucleótido del Ácido Nicotínico (NaMN) y Adenosín trifosfato (ATP); mediante la actividad catalítica de la Nicotinamida Mononucleótido Adenililtransferasa (NMNAT E.C. 2.7.7.1), presente en las dos rutas de biosíntesis del dinucleótido (Ruta de novo y de salvamento) [1][2]. Los parásitos protozoarios son causantes de enfermedades de alta incidencia en la salud pública, afectando a millones de personas por año. Actualmente algunas de estas enfermedades carecen de tratamientos efectivos, por lo cual es necesario identificar blancos terapéuticos para el control de estas [3]. La búsqueda de blancos farmacológicos se plantea a partir de un conocimiento racional de la biología molecular del parásito. En el laboratorio de Investigaciones Básicas en Bioquímica (LIBBIQ) se ha estudiado el metabolismo del NAD+ en parásitos intracelulares principalmente. El estudio de este proceso en parásitos extracelulares permitirá entender las relaciones parásito-hospedero y establecer los elementos relevantes de esta interacción [4]–[6]. En trabajos previos se ha encontrado una relación entre el número de enzimas de la familia NMNAT y la forma de vida parasitaria, caracterizada por la disminución de estas enzimas en organismos intracelulares con respecto a extracelulares. Por tanto, se realizó una aproximación experimental a la síntesis del NAD+ en parásitos extracelulares empleando como modelo Trichomonas vaginalis, para ello se implementaron estrategias de clonación y expresión de proteínas recombinantes, evaluando la actividad enzimática de dos isoenzimas generadoras de NAD+. Con lo cual, se identificaron dos NMNATs en T. vaginalis, siendo esta la primera aproximación al metabolismo del NAD+ de este dinucleótido de este parasito. Igualmente, se empleó una aproximación bioinformática en la búsqueda de candidatos a transportadores del NAD+ en parásitos extracelulares, con el propósito de establecer la relación síntesis/movilización del NAD+ en estos organismos. (Texto tomado de la fuente)spa
dc.description.abstractNicotinamide adenine dinucleotide (NAD + / NADH) is one of the main coenzymes in numerous cell oxidation-reduction processes, which is additionally involved in DNA repair, cell signaling, apoptosis, among others. The formation of NAD + occurs from nicotinamide mononucleotide (NMN) or nicotinic acid (NAMN) and adenosine triphosphate (ATP); through the catalytic activity of the Nicotinamide Mononucleotide Adenylyltransferase (NMNAT E.C. 2.7.7.1), present in the two dinucleotide biosynthesis pathways (de novo and salvage pathways) [1][2]. Protozoan parasites are the cause of diseases with a high incidence in public health, affecting millions of people per year. Currently some of these diseases lack effective treatments, which is why it is necessary to identify therapeutic targets to control them. [3]. The search for pharmacological targets arises from a rational knowledge of the molecular biology of the parasite. In the Laboratory of Basic Research in Biochemistry (LIBBIQ) the metabolism of NAD + has been studied mainly in intracellular parasites. The study of this process in extracellular parasites will make it possible to understand the parasite-host relationships and establish the relevant elements of this interaction. [4]–[6]. In previous works, a relationship has been found between the number of enzymes of the NMNAT family and the parasitic way of life, characterized by the decrease of these enzymes in intracellular organisms with respect to extracellular ones. Therefore, an experimental approach to the synthesis of NAD + in extracellular parasites was carried out using Trichomonas vaginalis as a model, for this, cloning and expression strategies of recombinant proteins were implemented, evaluating the enzymatic activity of two NAD + generating isoenzymes. Thus, two NMNATs were identified in T. vaginalis, this being the first approach to the metabolism of NAD + of this dinucleotide of this parasite. Likewise, a bioinformatic approach was used in the search for candidates for NAD + transporters in extracellular parasites, to establish the synthesis / mobilization relationship of NAD + in these organisms.eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Ciencias - Bioquímicaspa
dc.description.researchareaMetabolismo energético del NAD+spa
dc.format.extent128 páginasspa
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/82074
dc.language.isospaspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.departmentDepartamento de Químicaspa
dc.publisher.facultyFacultad de Cienciasspa
dc.publisher.placeBogotá, Colombiaspa
dc.publisher.programBogotá - Ciencias - Maestría en Ciencias - Bioquímicaspa
dc.relation.indexedRedColspa
dc.relation.indexedLaReferenciaspa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseReconocimiento 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/spa
dc.subject.ddc540 - Química y ciencias afinesspa
dc.subject.lembRELACION HUESPED-PARASITOspa
dc.subject.lembHost-parasite relationshipseng
dc.subject.otherNAD
dc.subject.proposalNAD+spa
dc.subject.proposalParásitos extracelularesspa
dc.subject.proposalNMNATspa
dc.subject.proposalTransportadores de nucleotidosspa
dc.subject.proposalExtracellular parasiteseng
dc.titleEl NAD+ en parásitos extracelulares: Procesos biosintéticos y de transportespa
dc.title.translatedNAD+ in extracellular parasites: Biosynthetic and transport processeseng
dc.typeTrabajo de grado - Maestríaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_bdccspa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/masterThesisspa
dc.type.redcolhttp://purl.org/redcol/resource_type/TMspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
dcterms.audience.professionaldevelopmentEstudiantesspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa

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