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Current Opinion in Chemical Biology Feb 2017Enzymatic transformations of primary, canonical metabolites generate active biomolecules that regulate important cellular and physiological processes. Roles include... (Review)
Review
Enzymatic transformations of primary, canonical metabolites generate active biomolecules that regulate important cellular and physiological processes. Roles include regulation of histone demethylation in epigenetics, inflammation in tissue injury, insulin sensitivity, cancer cell invasion, stem cell pluripotency status, inhibition of nitric oxide signaling and others. Such modified compounds, defined as epimetabolites, have functions distinct from classic hormones as well as removed from generic anabolism and catabolism. Epimetabolites are discovered by untargeted metabolomics using liquid- or gas chromatography-high resolution mass spectrometry and structurally annotated by in-silico fragmentation prediction tools. Their specific biological functions are subsequently investigated by targeted metabolomics methods.
Topics: Chromatography; Humans; Mass Spectrometry; Metabolome; Metabolomics; Molecular Structure; Software
PubMed: 28213207
DOI: 10.1016/j.cbpa.2017.01.012 -
PloS One 2018The potential of a metabolomics method to detect statistically significant perturbations in the metabolome of an organism is enhanced by excellent analytical precision,... (Comparative Study)
Comparative Study
The potential of a metabolomics method to detect statistically significant perturbations in the metabolome of an organism is enhanced by excellent analytical precision, unequivocal identification, and broad metabolomic coverage. While the former two metrics are usually associated with targeted metabolomics and the latter with non-targeted metabolomics, a systematic comparison of the performance of both approaches has not yet been carried out. The present work reports on the development and performance evaluation of separate targeted and non-targeted metabolomics methods. The targeted approach facilitated determination of 181 metabolites (quantitative analysis of 18 amino acids, 11 biogenic amines, 5 neurotransmitters, 5 nucleobases and semi-quantitative analysis of 50 carnitines, 83 phosphatidylcholines, and 9 sphingomyelins) using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and flow injection-tandem mass spectrometry (FI-MS/MS). Method accuracy and/or precision were assessed using replicate samples of NIST SRM1950 as well as fish liver and brain tissue from Gilthead Bream (Sparus aurata). The non-target approach involved UPLC-high resolution (Orbitrap) mass spectrometry (UPLC-HRMS). Testing of ionization mode and stationary phase revealed that a combination of positive electrospray ionization and HILIC chromatography produced the largest number of chromatographic features during non-target analysis. Furthermore, an evaluation of 4 different sequence drift correction algorithms, and combinations thereof, revealed that batchCorr produced the best precision in almost every test. However, even following correction of non-target data for signal drift, the precision of targeted data was better, confirming our existing assumptions about the strengths of targeted metabolomics. Finally, the accuracy of the online MS2-library mzCloud was evaluated using reference standards for 38 different metabolites. This is among the few studies that have systematically evaluated the performance of targeted and non-targeted metabolomics and provides new insight into the advantages and disadvantages of each approach.
Topics: Algorithms; Animals; Brain; Chromatography, Liquid; Fish Proteins; Humans; Liver; Mass Spectrometry; Metabolome; Metabolomics; Sea Bream
PubMed: 30439966
DOI: 10.1371/journal.pone.0207082 -
Drug Discovery Today Feb 2014Metabolism represents the 'sharp end' of systems biology, because changes in metabolite concentrations are necessarily amplified relative to changes in the... (Review)
Review
Metabolism represents the 'sharp end' of systems biology, because changes in metabolite concentrations are necessarily amplified relative to changes in the transcriptome, proteome and enzyme activities, which can be modulated by drugs. To understand such behaviour, we therefore need (and increasingly have) reliable consensus (community) models of the human metabolic network that include the important transporters. Small molecule 'drug' transporters are in fact metabolite transporters, because drugs bear structural similarities to metabolites known from the network reconstructions and from measurements of the metabolome. Recon2 represents the present state-of-the-art human metabolic network reconstruction; it can predict inter alia: (i) the effects of inborn errors of metabolism; (ii) which metabolites are exometabolites, and (iii) how metabolism varies between tissues and cellular compartments. However, even these qualitative network models are not yet complete. As our understanding improves so do we recognise more clearly the need for a systems (poly)pharmacology.
Topics: Biological Transport; Drug Discovery; Humans; Metabolic Networks and Pathways; Metabolism, Inborn Errors; Metabolome; Metabolomics; Models, Biological; Systems Biology
PubMed: 23892182
DOI: 10.1016/j.drudis.2013.07.014 -
Analytical and Bioanalytical Chemistry Jun 2022We introduce a new concept of yeast-derived biological matrix reference material for metabolomics research relying on in vivo synthesis of a defined biomass,...
We introduce a new concept of yeast-derived biological matrix reference material for metabolomics research relying on in vivo synthesis of a defined biomass, standardized extraction followed by absolute quantification with isotope dilution. The yeast Pichia pastoris was grown using full control- and online monitoring fed-batch fermentations followed by fast cold methanol quenching and boiling ethanol extraction. Dried extracts served for the quantification campaign. A metabolite panel of the evolutionarily conserved primary metabolome (amino acids, nucleotides, organic acids, and metabolites of the central carbon metabolism) was absolutely quantified by isotope dilution utilizing uniformly labeled C-yeast-based internal standards. The study involved two independent laboratories employing complementary mass spectrometry platforms, namely hydrophilic interaction liquid chromatography-high resolution mass spectrometry (HILIC-HRMS) and gas chromatography-tandem mass spectrometry (GC-MS/MS). Homogeneity, stability tests (on a panel of >70 metabolites over a period of 6 months), and excellent biological repeatability of independent fermentations over a period of 2 years showed the feasibility of producing biological reference materials on demand. The obtained control ranges proved to be fit for purpose as they were either superior or comparable to the established reference materials in the field.
Topics: Gas Chromatography-Mass Spectrometry; Isotopes; Metabolome; Metabolomics; Pichia; Saccharomyces cerevisiae; Tandem Mass Spectrometry
PubMed: 34642781
DOI: 10.1007/s00216-021-03694-w -
Trends in Parasitology Aug 2021Nearly half a million people die annually due to mosquito-borne diseases. Despite aggressive mosquito population-control efforts, current strategies are limited in their... (Review)
Review
Nearly half a million people die annually due to mosquito-borne diseases. Despite aggressive mosquito population-control efforts, current strategies are limited in their ability to control these vectors. A better understanding of mosquito metabolism through modern approaches can contribute to the discovery of novel metabolic targets and/or regulators and lead to the development of better mosquito-control strategies. Currently, cutting-edge technologies such as gas or liquid chromatography-mass spectrometry-based metabolomics are considered 'mature technologies' in many life-science disciplines but are still an emerging area of research in medical entomology. This review primarily discusses recent developments and progress in the application of mass spectrometry-based metabolomics to answer multiple biological questions related to mosquito metabolism.
Topics: Animals; Culicidae; Mass Spectrometry; Metabolome; Metabolomics
PubMed: 33896683
DOI: 10.1016/j.pt.2021.03.010 -
Circulation. Cardiovascular Genetics Apr 2017Through the measure of thousands of small-molecule metabolites in diverse biological systems, metabolomics now offers the potential for new insights into the factors... (Review)
Review
Through the measure of thousands of small-molecule metabolites in diverse biological systems, metabolomics now offers the potential for new insights into the factors that contribute to complex human diseases such as cardiovascular disease. Targeted metabolomics methods have already identified new molecular markers and metabolomic signatures of cardiovascular disease risk (including branched-chain amino acids, select unsaturated lipid species, and trimethylamine--oxide), thus in effect linking diverse exposures such as those from dietary intake and the microbiota with cardiometabolic traits. As technologies for metabolomics continue to evolve, the depth and breadth of small-molecule metabolite profiling in complex systems continue to advance rapidly, along with prospects for ongoing discovery. Current challenges facing the field of metabolomics include scaling throughput and technical capacity for metabolomics approaches, bioinformatic and chemoinformatic tools for handling large-scale metabolomics data, methods for elucidating the biochemical structure and function of novel metabolites, and strategies for determining the true clinical relevance of metabolites observed in association with cardiovascular disease outcomes. Progress made in addressing these challenges will allow metabolomics the potential to substantially affect diagnostics and therapeutics in cardiovascular medicine.
Topics: American Heart Association; Cardiovascular Diseases; Humans; Metabolome; Metabolomics; Microbiota; United States
PubMed: 28360086
DOI: 10.1161/HCG.0000000000000032 -
Molecules (Basel, Switzerland) May 2024As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening and... (Review)
Review
As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening and treatment, insight into understanding disease pathology and identifying potential targets. Metabolomics technology is crucial for discovering targets of small-molecule metabolites involved in disease phenotype. Mass spectrometry-based metabolomics has implemented in applications in various fields including target discovery, explanation of disease mechanisms and compound screening. It is used to analyze the physiological or pathological states of the organism by investigating the changes in endogenous small-molecule metabolites and associated metabolism from complex metabolic pathways in biological samples. The present review provides a critical update of high-throughput functional metabolomics techniques and diverse applications, and recommends the use of mass spectrometry-based metabolomics for discovering small-molecule metabolite signatures that provide valuable insights into metabolic targets. We also recommend using mass spectrometry-based metabolomics as a powerful tool for identifying and understanding metabolic patterns, metabolic targets and for efficacy evaluation of herbal medicine.
Topics: Metabolomics; Humans; Biomarkers; Mass Spectrometry; Drug Discovery; Metabolome; Animals
PubMed: 38792060
DOI: 10.3390/molecules29102198 -
International Journal of Molecular... Feb 2023Increasing attention has been focused on the study of protein-metabolite interactions (PMI), which play a key role in regulating protein functions and directing an... (Review)
Review
Increasing attention has been focused on the study of protein-metabolite interactions (PMI), which play a key role in regulating protein functions and directing an orchestra of cellular processes. The investigation of PMIs is complicated by the fact that many such interactions are extremely short-lived, which requires very high resolution in order to detect them. As in the case of protein-protein interactions, protein-metabolite interactions are still not clearly defined. Existing assays for detecting protein-metabolite interactions have an additional limitation in the form of a limited capacity to identify interacting metabolites. Thus, although recent advances in mass spectrometry allow the routine identification and quantification of thousands of proteins and metabolites today, they still need to be improved to provide a complete inventory of biological molecules, as well as all interactions between them. Multiomic studies aimed at deciphering the implementation of genetic information often end with the analysis of changes in metabolic pathways, as they constitute one of the most informative phenotypic layers. In this approach, the quantity and quality of knowledge about PMIs become vital to establishing the full scope of crosstalk between the proteome and the metabolome in a biological object of interest. In this review, we analyze the current state of investigation into the detection and annotation of protein-metabolite interactions, describe the recent progress in developing associated research methods, and attempt to deconstruct the very term "interaction" to advance the field of interactomics further.
Topics: Metabolomics; Proteomics; Metabolome; Proteome; Metabolic Networks and Pathways
PubMed: 36835565
DOI: 10.3390/ijms24044155 -
Biomolecules May 2018In this study, we elucidate that polyamine metabolite is a powerful biomarker to study post-radiation changes. Metabolomics in radiation biodosimetry, the application of... (Review)
Review
In this study, we elucidate that polyamine metabolite is a powerful biomarker to study post-radiation changes. Metabolomics in radiation biodosimetry, the application of a metabolomics analysis to the field of radiobiology, promises to increase the understanding of biological responses by ionizing radiation (IR). Radiation exposure triggers a complex network of molecular and cellular responses that impacts metabolic processes and alters the levels of metabolites. Such metabolites have potential as biomarkers for radiation dosimetry. Among metabolites, polyamine is one of many potential biomarkers to estimate radiation response. In addition, this review provides an opportunity for the understanding of a radiation metabolomics in biodosimetry and a polyamine case study.
Topics: Animals; Biomarkers; Biosensing Techniques; Humans; Metabolome; Metabolomics; Polyamines; Radiation Injuries; Radiation, Ionizing; Radiometry
PubMed: 29844258
DOI: 10.3390/biom8020034 -
Progress in Nuclear Magnetic Resonance... May 2017Metabolomics is undergoing tremendous growth and is being employed to solve a diversity of biological problems from environmental issues to the identification of... (Review)
Review
Metabolomics is undergoing tremendous growth and is being employed to solve a diversity of biological problems from environmental issues to the identification of biomarkers for human diseases. Nuclear magnetic resonance (NMR) and mass spectrometry (MS) are the analytical tools that are routinely, but separately, used to obtain metabolomics data sets due to their versatility, accessibility, and unique strengths. NMR requires minimal sample handling without the need for chromatography, is easily quantitative, and provides multiple means of metabolite identification, but is limited to detecting the most abundant metabolites (⩾1μM). Conversely, mass spectrometry has the ability to measure metabolites at very low concentrations (femtomolar to attomolar) and has a higher resolution (∼10-10) and dynamic range (∼10-10), but quantitation is a challenge and sample complexity may limit metabolite detection because of ion suppression. Consequently, liquid chromatography (LC) or gas chromatography (GC) is commonly employed in conjunction with MS, but this may lead to other sources of error. As a result, NMR and mass spectrometry are highly complementary, and combining the two techniques is likely to improve the overall quality of a study and enhance the coverage of the metabolome. While the majority of metabolomic studies use a single analytical source, there is a growing appreciation of the inherent value of combining NMR and MS for metabolomics. An overview of the current state of utilizing both NMR and MS for metabolomics will be presented.
Topics: Humans; Isotope Labeling; Magnetic Resonance Spectroscopy; Mass Spectrometry; Metabolome; Metabolomics
PubMed: 28552170
DOI: 10.1016/j.pnmrs.2017.01.001