title: The importance of accurately correcting for the natural abundance of stable isotopes.
abstract: The use of isotopically labeled tracer substrates is an experimental approach for measuring in vivo and in vitro intracellular metabolic dynamics. Stable isotopes that alter the mass but not the chemical behavior of a molecule are commonly used in isotope tracer studies. Because stable isotopes of some atoms naturally occur at non-negligible abundances, it is important to account for the natural abundance of these isotopes when analyzing data from isotope labeling experiments. Specifically, a distinction must be made between isotopes introduced experimentally via an isotopically labeled tracer and the isotopes naturally present at the start of an experiment. In this tutorial review, we explain the underlying theory of natural abundance correction of stable isotopes, a concept not always understood by metabolic researchers. We also provide a comparison of distinct methods for performing this correction and discuss natural abundance correction in the context of steady state13C metabolic flux, a method increasingly used to infer intracellular metabolic flux from isotope experiments.
authors.affiliation: Program in Computational Biology and Bioinformatics, Center for Genomic and Computational Biology & Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA. Electronic address: firas.midani@duke.edu.
authors.forename: Firas S
authors.initials: FS
authors.lastname: Midani
authors.affiliation: Department of Molecular & Integrative Physiology, Department of Computational Medicine & Bioinformatics and Brehm Center for Diabetes Research, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Internal Medicine, Division of Hematology and Oncology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: mlwynn@umich.edu.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Wynn
authors.affiliation: Department of Molecular & Integrative Physiology, Department of Computational Medicine & Bioinformatics and Brehm Center for Diabetes Research, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: schnells@umich.edu.
authors.forename: Santiago
authors.initials: S
authors.lastname: Schnell
mesh_terms: D002247:Carbon Isotopes / Q000737:chemistry; D005947:Glucose / Q000378:metabolism; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D064688:Metabolic Flux Analysis
chemical_list: D002247:Carbon Isotopes; D005947:Glucose
keywords: Metabolic flux analysis; Natural abundance correction; Reproducibility; Stable isotopes