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

Juvenile hormone (JH) regulates development and reproductive maturation in insects. The <i>corpora allata</i> (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...

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Autores principales: Martínez Rincón, Raúl O., Rivera Pérez, Crisalejandra, Diambra, Luis Aníbal, Noriega, Fernando G.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2017
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/87604
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id I19-R120-10915-87604
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Ciencias Exactas
Juvenile hormones
Biosynthesis
spellingShingle Ciencias Médicas
Ciencias Exactas
Juvenile hormones
Biosynthesis
Martínez Rincón, Raúl O.
Rivera Pérez, Crisalejandra
Diambra, Luis Aníbal
Noriega, Fernando G.
Modeling the flux of metabolites in the juvenile hormone biosynthesis pathway using generalized additive models and ordinary differential equations
topic_facet Ciencias Médicas
Ciencias Exactas
Juvenile hormones
Biosynthesis
description Juvenile hormone (JH) regulates development and reproductive maturation in insects. The <i>corpora allata</i> (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 <i>Aedes aegypti</i> 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 substrate 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 enzymatic 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.
format Articulo
Articulo
author Martínez Rincón, Raúl O.
Rivera Pérez, Crisalejandra
Diambra, Luis Aníbal
Noriega, Fernando G.
author_facet Martínez Rincón, Raúl O.
Rivera Pérez, Crisalejandra
Diambra, Luis Aníbal
Noriega, Fernando G.
author_sort Martínez Rincón, Raúl O.
title Modeling the flux of metabolites in the juvenile hormone biosynthesis pathway using generalized additive models and ordinary differential equations
title_short Modeling the flux of metabolites in the juvenile hormone biosynthesis pathway using generalized additive models and ordinary differential equations
title_full Modeling the flux of metabolites in the juvenile hormone biosynthesis pathway using generalized additive models and ordinary differential equations
title_fullStr Modeling the flux of metabolites in the juvenile hormone biosynthesis pathway using generalized additive models and ordinary differential equations
title_full_unstemmed Modeling the flux of metabolites in the juvenile hormone biosynthesis pathway using generalized additive models and ordinary differential equations
title_sort modeling the flux of metabolites in the juvenile hormone biosynthesis pathway using generalized additive models and ordinary differential equations
publishDate 2017
url http://sedici.unlp.edu.ar/handle/10915/87604
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