The Application of Stable Isotope Assisted Metabolomics in Biomedicine

Andre      Wegner; Thekla      Cordes; Alessandro      Michelucci; Karsten      Hiller

Abstract

During the last years, metabolomics has been established as a standard technique in biomedical research to analyze changes in metabolite levels. Currently, mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR) are the two major technologies to acquire metabolomics data. These technologies have been proven to be invaluable tools for the detection of disease related metabolic biomarkers. However, the obtained data only describe static metabolite concentrations and do not provide information about the dynamics of the system. Based on stable-isotope assisted metabolomics experiments, metabolic flux analysis (MFA) intends to quantitatively analyze intracellular metabolite conversion rates, thus providing a readout of enzyme activities. Although many studies have been published about disease related metabolomics, only a few publications about stable-isotope assisted metabolomics related to biomedicine are available. Especially in the context of personalized medicine, stable-isotope assisted technologies will become more important, since they provide patient and disease specific information about the metabolic state of the patient. In the following review we will point out the importance of stable-isotope related technologies for biomedical sciences. First, we will introduce analytical techniques required for metabolomics and MFA. In the second part, two biomedicine related stable-isotope based studies are summarized.

Keywords: Metabolomics, stable isotopes, metabolic flux analysis, biomedicine, mass spectrometry (MS), nuclear magnetic resonance spectroscopy, UHPLC/MSxMS injections, personalized medicine, stable-isotope assisted technologies, HPLC, cerebrospinal fluid (CSF), ice-cold methanol-water, chromatographic separation, dysregulations