From Exogenous to Endogenous: The Inevitable Imprint of Mass Spectrometry in Metabolomics

Department of Molecular Biology, The Scripps Center for Mass Spectrometry, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Journal of Proteome Research (Impact Factor: 4.25). 03/2007; 6(2):459-68. DOI: 10.1021/pr060505+
Source: PubMed


Mass spectrometry (MS) is an established technology in drug metabolite analysis and is now expanding into endogenous metabolite research. Its utility derives from its wide dynamic range, reproducible quantitative analysis, and the ability to analyze biofluids with extreme molecular complexity. The aims of developing mass spectrometry for metabolomics range from understanding basic biochemistry to biomarker discovery and the structural characterization of physiologically important metabolites. In this review, we will discuss the techniques involved in this exciting area and the current and future applications of this field.

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    • "FO-BEG1 into the medium during growth and to evaluate the effect of phosphate limitation on them, we performed an ultra-high resolution mass spectrometry analysis of the bacterial exo-metabolome. Mass spectrometry is the most widely used approach in metabolomic studies [14]. In particular high resolution accurate mass (HRAM) mass spectrometry instruments are receiving progressively more attention, owing to their ability to resolve highly complex samples and to yield accurate mass measurements, which allow precise calculations of the elemental composition [15], [16], [18]. "
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    ABSTRACT: Oceanic dissolved organic matter (DOM) is an assemblage of reduced carbon compounds, which results from biotic and abiotic processes. The biotic processes consist in either release or uptake of specific molecules by marine organisms. Heterotrophic bacteria have been mostly considered to influence the DOM composition by preferential uptake of certain compounds. However, they also secrete a variety of molecules depending on physiological state, environmental and growth conditions, but so far the full set of compounds secreted by these bacteria has never been investigated. In this study, we analyzed the exo-metabolome, metabolites secreted into the environment, of the heterotrophic marine bacterium Pseudovibrio sp. FO-BEG1 via ultra-high resolution mass spectrometry, comparing phosphate limited with phosphate surplus growth conditions. Bacteria belonging to the Pseudovibrio genus have been isolated worldwide, mainly from marine invertebrates and were described as metabolically versatile Alphaproteobacteria. We show that the exo-metabolome is unexpectedly large and diverse, consisting of hundreds of compounds that differ by their molecular formulae. It is characterized by a dynamic recycling of molecules, and it is drastically affected by the physiological state of the strain. Moreover, we show that phosphate limitation greatly influences both the amount and the composition of the secreted molecules. By assigning the detected masses to general chemical categories, we observed that under phosphate surplus conditions the secreted molecules were mainly peptides and highly unsaturated compounds. In contrast, under phosphate limitation the composition of the exo-metabolome changed during bacterial growth, showing an increase in highly unsaturated, phenolic, and polyphenolic compounds. Finally, we annotated the detected masses using multiple metabolite databases. These analyses suggested the presence of several masses analogue to masses of known bioactive compounds. However, the annotation was successful only for a minor part of the detected molecules, underlining the current gap in knowledge concerning the biosynthetic ability of marine heterotrophic bacteria.
    Full-text · Article · May 2014 · PLoS ONE
    • "Gas chromatography-mass spectrometry has been proven to be a potentially useful method for detection of small molecular metabolites based on its high sensitivity, peak resolution and reproducibility. Additionally, availability of the gas chromatography-mass spectrometry electron impact spectral library further facilitates the identification of diagnostic biomarkers and aids in the subsequent mechanistic elucidation of biological or pathological variations[29]. "
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    ABSTRACT: This study established an aged rat model of cognitive dysfunction using anesthesia with 2% isoflurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethylacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid (100 μmol/L). Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.
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    • "Owing to the rapid progresses in MS instrumentation during the past decade, MS has achieved much greater sensitivity than NMR in detecting small-molecule metabolites and thus can provide more comprehensive information on metabolite profile [23]. However, compared to NMR, MS also has several drawbacks, such as the need for sample preparation, irrecoverable sample loss during MS analysis, biased metabolite detection caused by inconsistent ionization efficiency in the MS instruments, and the lack of automatic metabolite identification [24]. "
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    ABSTRACT: Xenobiotic exposure, especially high-dose or repeated exposure of xenobiotics, can elicit detrimental effects on biological systems through diverse mechanisms. Changes in metabolic systems, including formation of reactive metabolites and disruption of endogenous metabolism, are not only the common consequences of toxic xenobiotic exposure, but in many cases are the major causes behind development of xenobiotic-induced toxicities (XIT). Therefore, examining the metabolic events associated with XIT generates mechanistic insights into the initiation and progression of XIT, and provides guidance for prevention and treatment. Traditional bioanalytical platforms that target only a few suspected metabolites are capable of validating the expected outcomes of xenobiotic exposure. However, these approaches lack the capacity to define global changes and to identify unexpected events in the metabolic system. Recent developments in high-throughput metabolomics have dramatically expanded the scope and potential of metabolite analysis. Among all analytical techniques adopted for metabolomics, liquid chromatography-mass spectrometry (LC-MS) has been most widely used for metabolomic investigations of XIT due to its versatility and sensitivity in metabolite analysis. In this review, technical platform of LC-MS-based metabolomics, including experimental model, sample preparation, instrumentation, and data analysis, are discussed. Applications of LC-MS-based metabolomics in exploratory and hypothesis-driven investigations of XIT are illustrated by case studies of xenobiotic metabolism and endogenous metabolism associated with xenobiotic exposure.
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