Tracing metabolic flux in vivo: motion pictures differ from snapshots

Abstract

Since Rudolf Schoenheimer’s pioneering metabolic tracing work in the 1930s1, it is currently well appreciated that all constituents of living matter (e.g., DNAs, RNAs, proteins, lipids, and metabolites) are in a constant state of turnover at varying rates to achieve overall “dynamic” homeostasis. Furthermore, metabolic systems are highly complex, connected, and interactive, and consequently, one’s metabolic fluxes (“motion pictures”) should not be understood as individual components but as a whole system2. Unfortunately, most modern metabolic studies heavily depend on the measurements of static, snapshot information, so-called “statomics” (e.g., transcriptomics, proteomics, metabolomics, and cellular signaling cascades) of individual components of the whole system, which often fail to reflect actual metabolic status3,4. Without simultaneous considerations of metabolic flux, sole dependence on “statomics” can lead to incorrect conclusions regarding metabolic status. In this Special Feature, experts in the field of tracer methodology or fluxomics provide the basic principles and applications of the methodologies determining metabolic fluxes to various metabolic conditions. The incorporation of these state-of-the-art methodologies into metabolic research will guide researchers to a better understanding of dynamic metabolic systems with which to better dissect underlying molecular mechanisms of physiology or pathophysiology.