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Article
Modeling the flux of metabolites in the juvenile hormone biosynthesis pathway using generalized additive models and ordinary differential equations
Biomolecular Sciences Institute: Faculty Publications
  • Raúl O. Martínez-Rincón, Centro de Investigaciones Biológicas del Noroeste (CIBNOR)
  • Crisalejandra Rivera-Pérez, Centro de Investigaciones Biológicas del Noroeste (CIBNOR)
  • Luis Diambra, Centro Regional de Estudios Genómicos (CREG)
  • Fernando G. Noriega, Department of Biological Sciences and Biomolecular Institute, Florida International University
Date of this Version
2-3-2017
Document Type
Article
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Abstract

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 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.

DOI
10.1371/journal.pone.0171516
Identifier
FIDC001609
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Originally published in PLoS One.

Creative Commons License
Creative Commons Attribution 4.0
Citation Information
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