A Mathematical Model of Phospholipid Biosynthesis

Mahsa Behzadi 1
1 AMIB - Algorithms and Models for Integrative Biology
LIX - Laboratoire d'informatique de l'École polytechnique [Palaiseau], LRI - Laboratoire de Recherche en Informatique, UP11 - Université Paris-Sud - Paris 11, Inria Saclay - Ile de France
Abstract : When measuring high-throughput data of cellular metabolism and its evolution, it is imperative to use appropriate models. These models allow the incorporation of these data into a coherent set. They also allow inter- pretation of the relevant metabolic variations and the key regulatory steps. Finally, they make contradictions apparent that question the basis on which the model itself is constructed. I use the experimental data of the metabolism of tumor cells in response to an anti-cancer treatment obtained in the biological laboratory. I focus on the modeling of a particular point: the metabolism of glyc- erophospholipids, which are good markers of cell proliferation. Phospho- lipids are essential parts of cell membranes and the study of their synthe- sis (especially mammalian cells) is therefore an important issue. In this work, our choice is to use a mathematical model by ordinary differential equations. This model relies essentially on hyperbolic equations (Michaelis- Menten) but also on kinetics, based on the law of mass action or on the diffusion. The model consists of 8 differential equations thus providing 8 substrates of interest. It has naturally some parameters which are unknown in vivo. Moreover some of them depend on the cellular conditions (cellular differentiation, pathologies). The model is a collection of the structure of the metabolic network, the writing of the stoichiometry matrix, generating the rate equations and finally differential equations. The chosen model is the mouse model (mouse / rat), because it is it- self a model of human. To study the relationship between the synthesis of phospholipids and cancer, several conditions are successively considered for the identification of parameters: - The healthy liver of the rat - The B16 melanoma and 3LL carcinoma line in mice, respectively, without treatment, during treatment with chloroethyl-nitrosourea and after treatment - Finally, the B16 melanoma in mice under methionine deprivation stress. In summary, my work provides a new interpretation of experimental data showing the essential role of PEMT enzyme and the superstable nature of 9 phospholipids metabolic network in carcinogenesis and cancer treatment. It shows the advantage of using a mathematical model in the interpretation of complex metabolic data.
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Submitted on : Saturday, December 10, 2011 - 10:47:51 AM
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  • HAL Id : tel-00650399, version 1



Mahsa Behzadi. A Mathematical Model of Phospholipid Biosynthesis. Bioinformatics [q-bio.QM]. Ecole Polytechnique X, 2011. English. ⟨tel-00650399⟩



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