Tracing metabolic flux in vivo: basic model structures of tracer methodology

• Published in: Experimental & molecular medicine 2022, 54(0), , pp.1-12
• Main Authors: Kim, Il-Young, Park, Sanghee, Kim, Yeongmin, Kim, Hee-Joo, Wolfe, Robert R.
• Format: Article
• Language: English
• Subjects: 101/58; 631/443/1338/2729; 692/308/575; Animals; Biomedical and Life Sciences; Biomedicine; Humans; Isotopes; Kinetics; Lipid metabolism; Lipids; Mass spectroscopy; Medical Biochemistry; Metabolic flux; Metabolic pathways; Metabolism; Metabolites; Molecular Medicine; mRNA; Polymers; Proteins - metabolism; Radioactive tracers; Radioisotopes; Review; Review Article; RNA, Messenger; Stem Cells; 생화학
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-022-00814-z

Molecules in living organisms are in a constant state of turnover at varying rates, i.e., synthesis, breakdown, oxidation, and/or conversion to different compounds. Despite the dynamic nature of biomolecules, metabolic research has focused heavily on static, snapshot information such as the abundances of mRNA, protein, and metabolites and/or (in)activation of molecular signaling, often leading to erroneous conclusions regarding metabolic status. Over the past century, stable, non-radioactive isotope tracers have been widely used to provide critical information on the dynamics of specific biomolecules (metabolites and polymers including lipids, proteins, and DNA), in studies in vitro in cells as well as in vivo in both animals and humans. In this review, we discuss (1) the historical background of the use of stable isotope tracer methodology in metabolic research; (2) the importance of obtaining kinetic information for a better understanding of metabolism; and (3) the basic principles and model structures of stable isotope tracer methodology using 13 C-, 15 N-, or 2 H-labeled tracers. Metabolism: Monitoring metabolic flux with stable isotope tracers Tagging biomolecules with stable isotopes of specific atoms can reveal details of the molecular inter-conversions of metabolism. The masses of the tracer isotopes used are greater than those of the more common atomic forms. This allows their movement through different metabolic pathways to be detected using mass spectrometry and modeling. Il-Young Kim at Gachon University School of Medicine in South Korea and colleagues focus their review on the use of stable, non-radioactive isotope tracers, especially, of carbon, nitrogen, and hydrogen, to study metabolism in live humans and other animals. They cover the basic model structures of tracer methodology that serve as the fundamental basis for various tracer methods available and the most recent applications. Their procedure is especially useful for monitoring the rates of metabolic inter-conversions, which can reveal aspects of health and disease.