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Annual Review of Biochemistry 2011Lipidomics, a major part of metabolomics, constitutes the detailed analysis and global characterization, both spatial and temporal, of the structure and function of... (Review)
Review
Lipidomics, a major part of metabolomics, constitutes the detailed analysis and global characterization, both spatial and temporal, of the structure and function of lipids (the lipidome) within a living system. As with proteomics, mass spectrometry has earned a central analytical role in lipidomics, and this role will continue to grow with technological developments. Currently, there exist two mass spectrometry-based lipidomics approaches, one based on a division of lipids into categories and classes prior to analysis, the "comprehensive lipidomics analysis by separation simplification" (CLASS), and the other in which all lipid species are analyzed together without prior separation, shotgun. In exploring the lipidome of various living systems, novel lipids are being discovered, and mass spectrometry is helping characterize their chemical structure. Deuterium exchange mass spectrometry (DXMS) is being used to investigate the association of lipids and membranes with proteins and enzymes, and imaging mass spectrometry (IMS) is being applied to the in situ analysis of lipids in tissues.
Topics: Animals; Cell Membrane; Humans; Lipids; Mass Spectrometry; Metabolomics; Models, Molecular; Molecular Structure; Protein Conformation; Proteomics
PubMed: 21469951
DOI: 10.1146/annurev-biochem-060409-092612 -
Molecules (Basel, Switzerland) Apr 2022Mass Spectrometry (MS) allows the analysis of proteins and peptides through a variety of methods, such as Electrospray Ionization-Mass Spectrometry (ESI-MS) or... (Review)
Review
Mass Spectrometry (MS) allows the analysis of proteins and peptides through a variety of methods, such as Electrospray Ionization-Mass Spectrometry (ESI-MS) or Matrix-Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-MS). These methods allow identification of the mass of a protein or a peptide as intact molecules or the identification of a protein through peptide-mass fingerprinting generated upon enzymatic digestion. Tandem mass spectrometry (MS/MS) allows the fragmentation of proteins and peptides to determine the amino acid sequence of proteins (top-down and middle-down proteomics) and peptides (bottom-up proteomics). Furthermore, tandem mass spectrometry also allows the identification of post-translational modifications (PTMs) of proteins and peptides. Here, we discuss the application of MS/MS in biomedical research, indicating specific examples for the identification of proteins or peptides and their PTMs as relevant biomarkers for diagnostic and therapy.
Topics: Amino Acid Sequence; Biomedical Research; Peptide Mapping; Peptides; Proteins; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tandem Mass Spectrometry
PubMed: 35458608
DOI: 10.3390/molecules27082411 -
Biochemical Society Transactions Jun 2022Structural Biology has moved beyond the aim of simply identifying the components of a cellular subsystem towards analysing the dynamics and interactions of multiple... (Review)
Review
Structural Biology has moved beyond the aim of simply identifying the components of a cellular subsystem towards analysing the dynamics and interactions of multiple players within a cell. This focal shift comes with additional requirements for the analytical tools used to investigate these systems of increased size and complexity, such as Native Mass Spectrometry, which has always been an important tool for structural biology. Scientific advance and recent developments, such as new ways to mimic a cell membrane for a membrane protein, have caused established methods to struggle to keep up with the increased demands. In this review, we summarize the possibilities, which Laser Induced Liquid Bead Ion Desorption (LILBID) mass spectrometry offers with regard to the challenges of modern structural biology, like increasingly complex sample composition, novel membrane mimics and advanced structural analysis, including next neighbor relations and the dynamics of complex formation.
Topics: Ions; Lasers; Mass Spectrometry; Membrane Proteins; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 35695670
DOI: 10.1042/BST20190881 -
Chemical Reviews Apr 2022Solution-phase hydrogen/deuterium exchange (HDX) coupled to mass spectrometry (MS) is a widespread tool for structural analysis across academia and the biopharmaceutical... (Review)
Review
Solution-phase hydrogen/deuterium exchange (HDX) coupled to mass spectrometry (MS) is a widespread tool for structural analysis across academia and the biopharmaceutical industry. By monitoring the exchangeability of backbone amide protons, HDX-MS can reveal information about higher-order structure and dynamics throughout a protein, can track protein folding pathways, map interaction sites, and assess conformational states of protein samples. The combination of the versatility of the hydrogen/deuterium exchange reaction with the sensitivity of mass spectrometry has enabled the study of extremely challenging protein systems, some of which cannot be suitably studied using other techniques. Improvements over the past three decades have continually increased throughput, robustness, and expanded the limits of what is feasible for HDX-MS investigations. To provide an overview for researchers seeking to utilize and derive the most from HDX-MS for protein structural analysis, we summarize the fundamental principles, basic methodology, strengths and weaknesses, and the established applications of HDX-MS while highlighting new developments and applications.
Topics: Deuterium; Deuterium Exchange Measurement; Hydrogen; Hydrogen Deuterium Exchange-Mass Spectrometry; Mass Spectrometry; Proteins
PubMed: 34493042
DOI: 10.1021/acs.chemrev.1c00279 -
Methods in Molecular Biology (Clifton,... 2014The field of metabolomics has witnessed an exponential growth in the last decade driven by important applications spanning a wide range of areas in the basic and life... (Review)
Review
The field of metabolomics has witnessed an exponential growth in the last decade driven by important applications spanning a wide range of areas in the basic and life sciences and beyond. Mass spectrometry in combination with chromatography and nuclear magnetic resonance are the two major analytical avenues for the analysis of metabolic species in complex biological mixtures. Owing to its inherent significantly higher sensitivity and fast data acquisition, MS plays an increasingly dominant role in the metabolomics field. Propelled by the need to develop simple methods to diagnose and manage the numerous and widespread human diseases, mass spectrometry has witnessed tremendous growth with advances in instrumentation, experimental methods, software, and databases. In response, the metabolomics field has moved far beyond qualitative methods and simple pattern recognition approaches to a range of global and targeted quantitative approaches that are now routinely used and provide reliable data, which instill greater confidence in the derived inferences. Powerful isotope labeling and tracing methods have become very popular. The newly emerging ambient ionization techniques such as desorption ionization and rapid evaporative ionization have allowed direct MS analysis in real time, as well as new MS imaging approaches. While the MS-based metabolomics has provided insights into metabolic pathways and fluxes, and metabolite biomarkers associated with numerous diseases, the increasing realization of the extremely high complexity of biological mixtures underscores numerous challenges including unknown metabolite identification, biomarker validation, and interlaboratory reproducibility that need to be dealt with for realization of the full potential of MS-based metabolomics. This chapter provides a glimpse at the current status of the mass spectrometry-based metabolomics field highlighting the opportunities and challenges.
Topics: Animals; Chromatography; Discriminant Analysis; Humans; Least-Squares Analysis; Mass Spectrometry; Metabolomics; Principal Component Analysis
PubMed: 25270919
DOI: 10.1007/978-1-4939-1258-2_1 -
Mass Spectrometry Reviews 2015Oxidative stress plays important roles in a wide range of diseases such as cancer, inflammatory disease, neurodegenerative disorders, etc. Tyrosine nitration in a... (Review)
Review
Oxidative stress plays important roles in a wide range of diseases such as cancer, inflammatory disease, neurodegenerative disorders, etc. Tyrosine nitration in a protein is a chemically stable oxidative modification, and a marker of oxidative injuries. Mass spectrometry (MS) is a key technique to identify nitrotyrosine-containing proteins and nitrotyrosine sites in endogenous and synthetic nitroproteins and nitropeptides. However, in vivo nitrotyrosine-containing proteins occur with extreme low-abundance to severely challenge the use of MS to identify in vivo nitroproteins and nitrotyrosine sites. A preferential enrichment of nitroproteins and/or nitropeptides is necessary before MS analysis. Current enrichment methods include immuno-affinity techniques, chemical derivation of the nitro group plus target isolations, followed with tandem mass spectrometry analysis. This article reviews the MS techniques and pertinent before-MS enrichment techniques for the identification of nitrotyrosine-containing proteins. This article reviews future trends in the field of nitroproteomics, including quantitative nitroproteomics, systems biological networks of nitroproteins, and structural biology study of tyrosine nitration to completely clarify the biological functions of tyrosine nitration.
Topics: Animals; Humans; Mass Spectrometry; Metabolic Networks and Pathways; Oxidative Stress; Proteins; Proteomics; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Systems Biology; Tandem Mass Spectrometry; Tyrosine
PubMed: 24318073
DOI: 10.1002/mas.21413 -
Journal of Mass Spectrometry : JMS May 2022This perspective gives an overview of the action spectroscopy methods for measurements of electronic, vibrational, and rotational spectra of mass-selected ions in the... (Review)
Review
This perspective gives an overview of the action spectroscopy methods for measurements of electronic, vibrational, and rotational spectra of mass-selected ions in the gas phase. We classify and give a short overview of the existing experimental approaches in this field. There is currently a plethora of names used for, essentially, the same techniques. Hence within this overview, we scrutinized the notations and suggested terms to be generally used. The selection was either driven by making the name unique and straightforward or the term being the most broadly used one. We believe that a simplification and a unification of the notation in ion spectroscopy can make this field better accessible for experts outside the mass spectrometry community where the applications of gas-phase action ion spectroscopy can make a large impact.
Topics: Ions; Mass Spectrometry; Spectrum Analysis
PubMed: 35434805
DOI: 10.1002/jms.4826 -
ACS Chemical Neuroscience May 2013Imaging mass spectrometry is an emerging technique of great potential for investigating the chemical architecture in biological matrices. Although the potential for... (Review)
Review
Imaging mass spectrometry is an emerging technique of great potential for investigating the chemical architecture in biological matrices. Although the potential for studying neurobiological systems is evident, the relevance of the technique for application in neuroscience is still in its infancy. In the present Review, a principal overview of the different approaches, including matrix assisted laser desorption ionization and secondary ion mass spectrometry, is provided with particular focus on their strengths and limitations for studying different neurochemical species in situ and in vitro. The potential of the various approaches is discussed based on both fundamental and biomedical neuroscience research. This Review aims to serve as a general guide to familiarize the neuroscience community and other biomedical researchers with the technique, highlighting its great potential and suitability for comprehensive and specific chemical imaging.
Topics: Animals; Brain Chemistry; Humans; Mass Spectrometry; Neurotransmitter Agents; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectrometry, Mass, Secondary Ion
PubMed: 23530951
DOI: 10.1021/cn400053c -
Analytical and Bioanalytical Chemistry Apr 2021Mass spectrometry imaging (MSI) provides insight into the molecular distribution of a broad range of compounds and, therefore, is frequently applied in the... (Comparative Study)
Comparative Study
Mass spectrometry imaging (MSI) provides insight into the molecular distribution of a broad range of compounds and, therefore, is frequently applied in the pharmaceutical industry. Pharmacokinetic and toxicological studies deploy MSI to localize potential drugs and their metabolites in biological tissues but currently require other analytical tools to quantify these pharmaceutical compounds in the same tissues. Quantitative mass spectrometry imaging (Q-MSI) is a field with challenges due to the high biological variability in samples combined with the limited sample cleanup and separation strategies available prior to MSI. In consequence, more selectivity in MSI instruments is required. This can be provided by multiple reaction monitoring (MRM) which uses specific precursor ion-product ion transitions. This targeted approach is in particular suitable for pharmaceutical compounds because their molecular identity is known prior to analysis. In this work, we compared different analytical platforms to assess the performance of MRM detection compared to other MS instruments/MS modes used in a Q-MSI workflow for two drug candidates (A and B). Limit of detection (LOD), linearity, and precision and accuracy of high and low quality control (QC) samples were compared between MS instruments/modes. MRM mode on a triple quadrupole mass spectrometer (QqQ) provided the best overall performance with the following results for compounds A and B: LOD 35.5 and 2.5 μg/g tissue, R 0.97 and 0.98 linearity, relative standard deviation QC <13.6%, and 97-112% accuracy. Other MS modes resulted in LOD 6.7-569.4 and 2.6-119.1 μg/g tissue, R 0.86-0.98 and 0.86-0.98 linearity, relative standard deviation QC < 19.4 and < 37.5%, and 70-356% and 64-398% accuracy for drug candidates A and B, respectively. In addition, we propose an optimized 3D printed mimetic tissue model to increase the overall analytical throughput of our approach for large animal studies. The MRM imaging platform was applied as proof-of-principle for quantitative detection of drug candidates A and B in four dog livers and compared to LC-MS. The Q-MSI concentrations differed <3.5 times with the concentrations observed by LC-MS. Our presented MRM-based Q-MSI approach provides a more selective and high-throughput analytical platform due to MRM specificity combined with an optimized 3D printed mimetic tissue model.
Topics: Animals; Dogs; Limit of Detection; Liver; Mass Spectrometry; Pharmaceutical Preparations
PubMed: 33770207
DOI: 10.1007/s00216-021-03210-0 -
Current Opinion in Chemical Biology Oct 2008Mass spectrometry has been widely used to analyze biological samples and has evolved into an indispensable tool for proteomics research. Our desire to understand the... (Review)
Review
Mass spectrometry has been widely used to analyze biological samples and has evolved into an indispensable tool for proteomics research. Our desire to understand the proteome has led to new technologies that push the boundary of mass spectrometry capabilities, which in return has allowed mass spectrometry to address an ever-increasing array of biological questions. The recent development of a novel mass spectrometer (Orbitrap) and new dissociation methods such as electron-transfer dissociation has made possible the exciting new areas of proteomic application. Although bottom-up proteomics (analysis of proteolytic peptide mixtures) remains the workhorse for proteomic analysis, middle-down and top-down strategies (analysis of longer peptides and intact proteins, respectively) should allow more complete characterization of protein isoforms and post-translational modifications. Finally, stable isotope labeling strategies have transformed mass spectrometry from merely descriptive to a tool for measuring dynamic changes in protein expression, interaction, and modification.
Topics: Animals; Humans; Mass Spectrometry; Molecular Weight; Protein Processing, Post-Translational; Proteins; Proteomics
PubMed: 18718552
DOI: 10.1016/j.cbpa.2008.07.024