Thursday 24 November 2016 - Understanding metabolic regulations using genome-scale metabolic model
Genome-scale metabolic model of hundreds of organisms has been successfully used by a variety of systems biology tools to understand the system level dynamics. Flux balance analysis (FBA) is one such powerful tool which uses topology of metabolic reactions and predict steady state flux profile. This approach, so far, has not been able to combine regulatory information such as metabolite-enzyme inhibitory reactions together with metabolite-enzyme metabolic reactions. Metabolic enzyme inhibition is studied for a long time on individual proteins, but there is limited knowledge about its global metabolic importance. We generated a genome-spanning inhibitor network, by merging enzymological knowledge that accumulated over a century with the human metabolic reconstruction. We find that virtually every biochemical process is sensitive to metabolite inhibition, and reveal strong preferences between metabolite classes to inhibit specific enzyme mechanisms. Most of enzyme inhibition is competitive and explained by the finite structural diversity within the metabolome. Finally, essential metabolites inhibit more reactions as less important metabolites, while in eukaryotes, organelle-localized enzymes are protected from enzyme inhibition. Hence, cellular metabolism is constrained by the structural diversity that prevails within the metabolome, so that metabolism evolves against metabolite-enzyme interactions.
Dr Mohammad Tauqeer Alam has recently started as a Senior Research Fellow (Bioinformatics) at the Warwick medical school. He is mainly interested in applying mathematical modeling approach to understand metabolic regulations at different level of cellular process. He combines genome-scale models with '-Omics' datasets and examine how cell re-organizes its metabolism due to genetic or environmental perturbations. Before joining WMS, he was a post-doctoral researcher at the University of Cambridge. There, he studied Yeast metabolism. In his PhD, Dr. Alam applied genome-scale models to understand the mechanisms involved in the production of antibiotics in Streptomyces species
Dr Mohammad Tauqeer Alam