hydrophobicity and charge shape cellular metabolite concentrations疏水性和电荷形状细胞代谢物浓度.pdfVIP

Hydrophobicity and Charge Shape Cellular Metabolite Concentrations 1 1 1 2 1 Arren Bar-Even , Elad Noor , Avi Flamholz , Joerg M. Buescher , Ron Milo * 1 Department of Plant Sciences, The Weizmann Institute of Science, Rehovot, Israel, 2 Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland Abstract What governs the concentrations of metabolites within living cells? Beyond specific metabolic and enzymatic considerations, are there global trends that affect their values? We hypothesize that the physico-chemical properties of metabolites considerably affect their in-vivo concentrations. The recently achieved experimental capability to measure the concentrations of many metabolites simultaneously has made the testing of this hypothesis possible. Here, we analyze such recently available data sets of metabolite concentrations within E. coli, S. cerevisiae, B. subtilis and human. Overall, these data sets encompass more than twenty conditions, each containing dozens (28-108) of simultaneously measured metabolites. We test for correlations with various physico-chemical properties and find that the number of charged atoms, non-polar surface area, lipophilicity and solubility consistently correlate with concentration. In most data sets, a change in one of these properties elicits a ,100 fold increase in metabolite concentrations. We find that the non-polar surface area and number of charged atoms account for almost half of the variation in concentrations in the most reliable and comprehensive data set. Analyzing specific groups of metabolites, such as amino-acids or phosphorylated nucleotides, reveals even a higher dependence of concentration on hydrophobicity. We suggest that these findi