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Modeling the flux of metabolites in the juvenile hormone biosynthesis pathway using generalized additive models and ordinary differential equations

dc.creatorRAUL OCTAVIO MARTINEZ RINCON
dc.creatorCRISALEJANDRA RIVERA PEREZ
dc.creatorFernando Gabriel Noriega
dc.creatorLuis Diambra
dc.date2017
dc.identifierhttp://cibnor.repositorioinstitucional.mx/jspui/handle/1001/636
dc.identifier.urihttp://dspace.cibnor.mx:8080/handle/123456789/642
dc.description"Juvenile hormone (JH) regulates development and reproductive maturation in insects. The corpora allata (CA) from female adult mosquitoes synthesize fluctuating levels of JH, which have been linked to the ovarian development and are influenced by nutritional signals. The rate of JH biosynthesis is controlled by the rate of flux of isoprenoids in the pathway, which is the outcome of a complex interplay of changes in precursor pools and enzyme levels. A comprehensive study of the changes in enzymatic activities and precursor pool sizes have been previously reported for the mosquito Aedes aegypti JH biosynthesis pathway. In the present studies, we used two different quantitative approaches to describe and predict how changes in the individual metabolic reactions in the pathway affect JH synthesis. First, we constructed generalized additive models (GAMs) that described the association between changes in specific metabolite concentrations with changes in enzymatic activities and sub-strate concentrations. Changes in substrate concentrations explained 50% or more of the model deviances in 7 of the 13 metabolic steps analyzed. Addition of information on enzy-matic activities almost always improved the fitness of GAMs built solely based on substrate concentrations. GAMs were validated using experimental data that were not included when the model was built. In addition, a system of ordinary differential equations (ODE) was developed to describe the instantaneous changes in metabolites as a function of the levels of enzymatic catalytic activities. The results demonstrated the ability of the models to predict changes in the flux of metabolites in the JH pathway, and can be used in the future to design and validate experimental manipulations of JH synthesis."
dc.formatapplication/pdf
dc.languageeng
dc.relationinfo:eu-repo/semantics/dataset/DOI/DOI: 10.1371/journal.pone.0171516
dc.relationinfo:eu-repo/semantics/altIdentifier/DOI/DOI: 10.1371/journal.pone.0171516
dc.relationinfo:eu-repo/semantics/reference/URL/URL: http://journals.plos.org/plosone
dc.relationcitation:Martínez-Rincón RO, Rivera-Pérez C, Diambra L, Noriega FG (2017) Modeling the flux of metabolites in the juvenile hormone biosynthesis pathway using generalized additive models and ordinary differential equations. PLoS ONE 12(2): e0171516. doi:10.1371/journal.pone.0171516
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/4.0
dc.sourcePlos One
dc.subjectinfo:eu-repo/classification/AUTOR/Enzymes, Enzyme precursors, Metabolic pathways, Metabolites, Bone and mineral metabolism, Mosquitoes, Biosynthesis
dc.subjectinfo:eu-repo/classification/cti/2
dc.subjectinfo:eu-repo/classification/cti/24
dc.subjectinfo:eu-repo/classification/cti/2403
dc.subjectinfo:eu-repo/classification/cti/230209
dc.titleModeling the flux of metabolites in the juvenile hormone biosynthesis pathway using generalized additive models and ordinary differential equations
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion


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