Absolute quantification of all metabolic enzymes by information-based proteomics and computational analysis for cancer metabolism

      Ten years after completion of Human Genome Project, fundamental principles operating living organisms remains poorly understood. Given that proteins serve as direct functional devices for biochemical reactions, comprehensive quantification of proteins is thus an essential step for application of systems biology. We have developed a new technology termed information-based multiple reaction monitoring (iMRM) to measure the absolute abundance of all human proteins. With the use of iMRM system, we have measured the absolute abundance of all metabolic enzymes in normal and cancer cells, and uncovered the global metabolic shift accompanied by transformation. In addition, we developed a new computational method to integrate absolute quantity of metabolic enzymes, as well as those of metabolites, experimentally available fluxes and metabolic network structure. We can now estimate each flux, calculate sensitivities of each enzyme on each flux and metabolite and simulate metabolite concentrations under some perturbations. We expect that the development of these approaches might lead to comprehensive understanding as to how the network systems is regulated in normal and cancer metabolism.