Metabolomics and metabolic models

A knowledge of the simple structure of gene interaction networks may lead to hypotheses about their dynamics. The construction of a model may then permit clarification and comparison with experimental data.

The study of topologic models within a heterogeneous network including regulatory and protein-protein interactions has led to the identification of an adaptive system of regulation in yeast (Saccharomyces cerevisiae). Modeling of this system which includes a feedback loop has led to the formulation of new hypotheses about its function. The interactions between galactose and three proteins, Gal3p, Gal80p and Gal4p determine the transcriptional state of the genes required for the assimilation of galactose. After an augmentation in the concentration of galactose, the galactose molecules bind to Gal3p. This results, via Gal80p, in the activation of Gal4p which then induces the transcription of the GAL3 and GAL80 genes. The feedback loop is closed by the capture of Gal4p by the newly-synthesized proteins Gal3p and Gal80p, which leads to a decrease in the transcriptional activity of Gal4p. If galactose is considered to be the entry signal and Gal4p as the exit, the system behaves like a derived filter.

The advantage for the cell of such a system is to only produce enzymes for the degradation of galactose in proportion to the concentration of galactose in the medium. The mechanism also makes it possible to maintain sensitivity over a large range of variation in the concentration of galactose, by limiting the quantity of the receptor necessary.