H OH metabolites OH Review Metabolic Flux Analysis—Linking Isotope Labeling and Metabolic Fluxes Yujue Wang 1,2, Fredric E. Wondisford 1, Chi Song 3, Teng Zhang 4 and Xiaoyang Su 1,2,* 1 Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA;
[email protected] (Y.W.);
[email protected] (F.E.W.) 2 Metabolomics Shared Resource, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA 3 Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, OH 43210, USA;
[email protected] 4 Department of Mathematics, University of Central Florida, Orlando, FL 32816, USA;
[email protected] * Correspondence:
[email protected]; Tel.: +1-732-235-5447 Received: 14 September 2020; Accepted: 4 November 2020; Published: 6 November 2020 Abstract: Metabolic flux analysis (MFA) is an increasingly important tool to study metabolism quantitatively. Unlike the concentrations of metabolites, the fluxes, which are the rates at which intracellular metabolites interconvert, are not directly measurable. MFA uses stable isotope labeled tracers to reveal information related to the fluxes. The conceptual idea of MFA is that in tracer experiments the isotope labeling patterns of intracellular metabolites are determined by the fluxes, therefore by measuring the labeling patterns we can infer the fluxes in the network. In this review, we will discuss the basic concept of MFA using a simplified upper glycolysis network as an example. We will show how the fluxes are reflected in the isotope labeling patterns. The central idea we wish to deliver is that under metabolic and isotopic steady-state the labeling pattern of a metabolite is the flux-weighted average of the substrates’ labeling patterns.