Tracing metabolic flux through time and space with isotope labeling experiments

Metabolism is dynamic and must function in context-specific ways to adjust to changes in the surrounding cellular and ecological environment. When isotopic tracers are used, metabolite flow (i.e. metabolic flux) can be quantified through biochemical networks to assess metabolic pathway operation. The cellular activities considered across multiple tissues and organs result in the observed phenotype and can be analyzed to discover emergent, whole-system properties of biology and elucidate misconceptions about network operation. However, temporal and spatial challenges remain significant hurdles and require novel approaches and creative solutions. We survey current investigations in higher plant and animal systems focused on dynamic isotope labeling experiments, spatially resolved measurement strategies, and observations from re-analysis of our own studies that suggest prospects for future work. Related discoveries will be necessary to push the frontier of our understanding of metabolism to suggest novel solutions to cure disease and feed a growing future world population.