A timeline of stable isotopes and mass spectrometry in the life sciences

Abstract

This review retraces the role of stable isotopes and mass spectrometry in the life sciences. The timeline is divided into four segments covering the years 1920-1950, 1950-1980, 1980-2000, and 2000 until today. For each period methodic progress and typical applications are discussed. Application of stable isotopes is driven by improvements of mass spectrometry, chromatography, and related fields in sensitivity, mass accuracy, structural specificity, complex sample handling ability, data output, and data evaluation. We currently experience the vision of omics-type analyses, that is, the comprehensive identification and quantification of a complete compound class within one or a few analytical runs. This development is driven by stable isotopes without competition by radioisotopes. In metabolic studies as classic field of isotopic tracer experiments, stable isotopes and radioisotopes were competing solutions, with stable isotopes as the long-term junior partner. Since the 1990s the number of metabolic studies with radioisotopes decreases, whereas stable isotope studies retain their slow but stable upward tendency. Unique fields of stable isotopes are metabolic tests in newborns, metabolic experiments in healthy controls, newborn screening for inborn errors, quantification of drugs and drug metabolites in doping control, natural isotope fractionation in geology, ecology, food authentication, or doping control, and more recently the field of quantitative omics-type analyses. There, cells or whole organisms are systematically labeled with stable isotopes to study proteomic differences or specific responses to stimuli or genetic manipulation. The duo of stable isotopes and mass spectrometry will probably continue to grow in the life sciences, since it delivers reference-quality quantitative data with molecular specificity, often combined with informative isotope effects. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:58-85, 2017.

Exploring ribosome composition and newly synthesized proteins through proteomics and potential biomedical applications

“…For example, for quantification of Drosophila (fruit fly) proteomes [45], for preparation of 15 N-labeled protein standards from mice to compare unlabeled proteomes [46], for identification of variation in expression and turnover of dihydropyrimidinase-related proteins DPYSL3 and DPYSL5 during brain development by incorporation of 15 N into mice diet [47], and for determination of protein turnover rates on whole proteome scale by restricting all the nitrogen in the rodent diet to 15 N (spirulina algae) with reversion to normal 14 N diet with time points at days to years [48]. In addition, there have been various reviews published discussing both the strengths and the weaknesses of chemical and metabolic labeling of model organisms [49], the merits and difficulties of labeling methods for assessing protein turnover and dynamics [50–51], and a review article of stable isotopes and mass spectrometry in life sciences covering a time period from 1920 to 2016 [52]. Since SILAC and non-canonical amino acids labeling are discussed later in more details as the techniques of proteomic workflow used for metabolic labeling of newly synthesized proteins and their enrichment, identification and quantitation in the cells, tissues or whole animals, the brief basic description of each technique is included in following sections.…”

Optimization of Experiment Design for Mass Spectrometric Isotopic Labeling Kinetics

“…Metabolism has been studied with isotopes for nearly a century, including with stable isotopes [reviewed in (Lehmann, 2017)]. Such kinetic isotopic measurements have the benefit of yielding absolute rates of metabolism, especially when combined with isotopomeric analysis of stable isotopes (Alves et al, 2015;Chance et al, 1983;Gruetter et al, 1994;Katz et al, 1993;Malloy et al, 1987).…”

Isotope labeling to determine the dynamics of metabolic response in CHO cell perfusion bioreactors using MALDI‐TOF‐MS

“…The metabolic understanding gained has been used to advance cell line engineering and media design in biopharmaceutical development . The analytical tools to quantify isotope pattern typically rely on mass spectrometry (MS), tandem‐mass spectrometry (MS/MS), and nuclear magnetic resonance (NMR) spectroscopy . In particular, matrix‐assisted laser desorption/ionization (MALDI) time‐of‐flight mass spectrometry (TOF‐MS) has become a valuable tool, given its simple sample preparation, data analysis and sensitivity to high‐mass metabolites .…”

“…23,24 The analytical tools to quantify isotope pattern typically rely on mass spectrometry (MS), tandem-mass spectrometry (MS/MS), and nuclear magnetic resonance (NMR) spectroscopy. 18,25,26 In particular, matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) has become a valuable tool, given its simple sample preparation, data analysis and sensitivity to high-mass metabolites. 27 In combination with the use of microarrays (MAMS), good reproducibility, and semiquantitative estimation capabilities have been shown in the high throughput analysis of intracellular metabolites in mammalian cell cultures.…”