Towards high resolution analysis of metabolic flux in cells and tissues

•The metabolic state of a cell is an important determinant of cellular phenotype.•Current methods for global metabolic flux quantification characterize bulk behavior.•Genome-scale models offer promise for analyses involving multiple cell types.•Advances in metabolic imaging could afford spatiotemporally resolved analysis. Metabolism extracts chemical energy from nutrients, uses this energy to form building blocks for biosynthesis, and interconverts between various small molecules that coordinate the activities of cellular pathways. The metabolic state of a cell is increasingly recognized to determine the phenotype of not only metabolically active cell types such as liver, muscle, and adipose, but also other specialized cell types such as neurons and immune cells. This review focuses on methods to quantify intracellular reaction flux as a measure of cellular metabolic activity, with emphasis on studies involving cells of mammalian tissue. Two key areas are highlighted for future development, single cell metabolomics and noninvasive imaging, which could enable spatiotemporally resolved analysis and thereby overcome issues of heterogeneity, a distinctive feature of tissue metabolism