Single-cell and bulk level metabolomic study of the glycolysis inhibition by 2-deoxy-D-glucose in Saccharomyces cerevisiae

Single-cell level measurements are necessary to characterize the intrinsic biological variability in a population of cells. In a study of the metabolic response of a clonal Saccharomyces cerevisiae population challenged by the glycolytic inhibitor 2-deoxy-D-glucose (2-DG), this variability is shown here, by comparing measurements at the population and the single-cell level. A novel microarray platform and MALDI mass spectrometric read-out allow us to follow 24 parameters simultaneously, in up to 100 single-cell measurements. Correlation plots for metabolites from the glycolytic pathway, the pentose phosphate pathway, and the observed ATP/ADP ratio as a measure of cellular energy charge give new insight into biochemical and metabolic pathways, which would not be accessible from population-level metabolomics data. Single-cell level measurements are necessary to characterize the intrinsic biological variability in a population of cells. In this study we demonstrate that with the Microarrays for Mass Spectrometry (MAMS) platform we are able to observe this variability. We monitor environmentally-(2-deoxy-D-glucose) and genetically-(∆PFK2) perturbed Saccharomyces cerevisiae cells both at the population and near single-cell levels. Correlation plots between metabolites from the glycolytic pathway, as well as with the observed ATP/ADP ratio as a measure of cellular energy charge give new biological insight that is not accessible from population-level metabolomic data.