Reconstruction of metabolic networks from high-throughput metabolite profiling data: in silico analysis of red blood cell metabolism

We investigate the ability of algorithms developed for reverse engineering of transcriptional regulatory networks to reconstruct metabolic networks from high-throughput metabolite profiling data. For this, we generate synthetic metabolic profiles for benchmarking purposes based on a well-established model for red blood cell metabolism. A variety of data sets is generated, accounting for different properties of real metabolic networks, such as experimental noise, metabolite correlations, and temporal dynamics. These data sets are made available online. We apply ARACNE, a mainstream transcriptional networks reverse engineering algorithm, to these data sets and observe performance comparable to that obtained in the transcriptional domain, for which the algorithm was originally designed.Comment: 14 pages, 3 figures. Presented at the DIMACS Workshop on Dialogue on Reverse Engineering Assessment and Methods (DREAM), Sep 200

Regulation of Inflammation by Short Chain Fatty Acids

The short chain fatty acids (SCFAs) acetate (C2), propionate (C3) and butyrate (C4) are the main metabolic products of anaerobic bacteria fermentation in the intestine. In addition to their important role as fuel for intestinal epithelial cells, SCFAs modulate different processes in the gastrointestinal (GI) tract such as electrolyte and water absorption. These fatty acids have been recognized as potential mediators involved in the effects of gut microbiota on intestinal immune function. SCFAs act on leukocytes and endothelial cells through at least two mechanisms: activation of GPCRs (GPR41 and GPR43) and inhibiton of histone deacetylase (HDAC). SCFAs regulate several leukocyte functions including production of cytokines (TNF-α, IL-2, IL-6 and IL-10), eicosanoids and chemokines (e.g., MCP-1 and CINC-2). The ability of leukocytes to migrate to the foci of inflammation and to destroy microbial pathogens also seems to be affected by the SCFAs. In this review, the latest research that describes how SCFAs regulate the inflammatory process is presented. The effects of these fatty acids on isolated cells (leukocytes, endothelial and intestinal epithelial cells) and, particularly, on the recruitment and activation of leukocytes are discussed. Therapeutic application of these fatty acids for the treatment of inflammatory pathologies is also highlighted

A kinetic model of phosphofructokinase from plasmodium berghei—application of a novel procedure for model discrimination

AbstractA novel statistical procedure is applied to discriminate between several alternative kinetic models of the glycolytic control enzyme phosphofructokinase from the malarial parasite Plasmodium berghei. Among the Monod-models, assuming different reaction mechanisms and various modes of allosteric regulation by ATP, F6P and pH, one model was favoured which was shown to provide an adequate description of the data