In fact, a genome scale reconstruction of human metabolism has been completed, called selleck inhibitor Recon 1. Recon 1 is a global human knowledge base of biochemical transformations in humans that is not cell or tissue specific. More recently, Recon 1 has been adapted to study specific cells and tissues with the help of high throughput data, including the human brain, liver, kidney, Inhibitors,Modulators,Libraries and alveolar macrophage. Though many cell and tissue specific models have been reconstructed from Recon 1, the human erythro cyte has undeservedly received less attention as the cell has been largely assumed to be simple. Histori cally, red cell metabolic models began with simple gly colytic models. In a fifteen year period, the original mathematical model was updated to include the pentose phosphate pathway, Rapoport Luebering shunt, and adenine nucleotide salvage pathways.
More recent metabolic models have been built accounting for additional regulatory and metabolic components. However, in the past decade, attempts to obtain comprehensive proteo mic coverage Inhibitors,Modulators,Libraries of the red cell have demonstrated a much richer complement of metabolism than pre viously anticipated. Modeling the unexpected complexity of erythrocyte metabolism is critical to further understanding the red cell and its interactions with other human cells and tissues. Thus, we use available proteomics to develop the largest in silico model of metabolism of the human red cell to date. Though comprehensive proteomic data provides an overview of red cell proteins, we believe it does not provide a full functional assessment of erythrocyte metabolism.
Thus, we have also gathered 50 years of erythrocyte experimental studies in the form of 60 peer reviewed articles and books to manually curate the final model. In order to objectively test physiological functionality, we have put the final model through rigorous simulation. Results and Discussion iAB RBC 283 is a proteomic based metabolic Inhibitors,Modulators,Libraries recon struction and a biochemical knowledge base, a func tional integration of high throughput biological data and existing experimentally verified biochemical erythrocyte knowledge that can be queried Inhibitors,Modulators,Libraries through simulations and calculations. We first describe the process and charac terize the new erythrocyte reconstruction and determine the metabolic functionality. Then, we analyze the results by mapping genetic polymorphisms and drug target information onto the network.
Proteomic based erythrocyte reconstruction Inhibitors,Modulators,Libraries Proteomic data has been successfully used for recon structions of Thermotoga maritima and the human mitochondria and provides direct evidence of a cells ability to carry out specific enzymatic reactions. One challenge in the measurement of proteomic more data is the depth of coverage, which is still known to be incom plete, even for studies aiming to obtain comprehensive coverage.