Molecular phenomics of a high-calorie diet-induced porcine model of prepubertal obesity.

As obesity incidence is alarmingly rising among young individuals, we aimed to characterize an experimental model of this situation, considering the similarity between human and porcine physiology. For this reason, we fed prepubertal (63 days old) Duroc breed females (n=21) either with a standard growth diet (3800 kcal/day) or one with a high-calorie content (5200 kcal/day) during 70 days. Computerized tomography, mass-spectrometry-based metabolomics and lipidomics, as well as peripheral blood mononuclear cell transcriptomics, were applied to define traits linked to high-calorie intake.

An optimized algorithm for flux estimation from isotopomer distribution in glucose metabolites.

Motivation: Analysis of the conversion of (13)C glucose within the metabolic network allows the evaluation of the biochemical fluxes in interconnecting metabolic pathways. Such analyses require solving hundreds of equations with respect to individual isotopomer concentrations, and this assumes applying special software even for constructing the equations. The algorithm, proposed by others could be improved.

Quantitative characterization of homo- and heteroassociations of muscle phosphofructokinase with aldolase.

Dissociation of purified phosphofructokinase accompanied with inactivation was analyzed in the absence and presence of aldolase and the data were compared with those obtained with muscle extract. The kinetics of the decrease in enzymatic activity was highly dependent on the dilution factor in both cases, but the inactivation appeared to be biphasic only with extract. The inactivation of the phosphofructokinase was impeded by addition of excess of aldolase.

Advantages and disadvantages of aggregating fluxes into synthetic and degradative fluxes when modelling metabolic pathways.

It is now widely accepted that mathematical models are needed to predict the behaviour of complex metabolic networks in the cell, in order to have a rational basis for planning metabolic engineering with biotechnological or therapeutical purposes. The great complexity of metabolic networks makes it crucial to simplify them for analysis, but without violating key principles of stoichiometry or thermodynamics. We show here, however, that models for branched complex systems are sometimes obtained that violate the stoichiometry of fluxes at branch points and as a result give unrealistic metabolite concentrations at the steady state.