We present a novel
approach for the increasing reliability of compound
identification for LC-MS and MALDI imaging lipidomics. Our approach
is based on the characterization of compounds not only by the elution
time, accurate mass, and fragmentation spectra but also by the number
of labile hydrogens that can be measured using the hydrogen/deuterium
(H/D) exchange approach. The number of labile hydrogens (those from
−OH and −NH groups) serves as an additional structural
descriptor used when performing a database search. For LC-MS experiment,
the H/D exchange was performed in the heating capillary of the modified
electrospray ionization (ESI) source, while for MALDI imaging, the
exchange was performed in the ion funnel at 10 Torr pressure. It was
observed that such an approach allowed one to achieve a considerable
degree of deuteration, enough to unambiguously distinguish between
different classes of lipids. The proposed analytical approach may
be successfully used for the identification not only of lipids but
also of peptides and metabolites. A special software for the automatic
filtration of molecules based on the number of functional groups was
also developed.
Cells metabolism alteration is the new hallmark of cancer, as well as an important method for
carcinogenesis investigation. It is well known that the malignant cells switch to aerobic glycolysis pathway
occurring also in healthy proliferating cells. Recently, it was shown that in malignant cells de novo
synthesis of the intracellular fatty acid replaces dietary fatty acids which change the lipid composition of
cancer cells noticeably. These alterations in energy metabolism and structural lipid production explain
the high proliferation rate of malignant tissues. However, metabolic reprogramming affects not only
lipid metabolism but many of the metabolic pathways in the cell. 2-hydroxyglutarate was considered as
cancer cell biomarker and its presence is associated with oxidative stress influencing the mitochondria
functions. Among the variety of metabolite detection methods, mass spectrometry stands out as the most
effective method for simultaneous identification and quantification of the metabolites. As the metabolic
reprogramming is tightly connected with epigenetics and signaling modifications, the evaluation of metabolite
alterations in cells is a promising approach to investigate the carcinogenesis which is necessary
for improving current diagnostic capabilities and therapeutic capabilities. In this paper, we overview
recent studies on metabolic alteration and oncometabolites, especially concerning brain cancer and mass
spectrometry approaches which are now in use for the investigation of the metabolic pathway.
Graphical abstract
Native mass spectrometry (MS) enjoyed tremendous success in the past two decades in a wide range of studies aiming at understanding the molecular mechanisms of physiological processes underlying a variety of pathologies and accelerating the drug discovery process. However, the success record of native MS has been surprisingly modest with respect to the most recent challenge facing the biomedical community—the novel coronavirus infection (COVID-19). The major reason for the paucity of successful studies that use native MS to target various aspects of SARS-CoV-2 interaction with its host is the extreme degree of heterogeneity of the viral protein playing a key role in the host cell invasion. Indeed, the SARS-CoV-2 spike protein (S-protein) is extensively glycosylated, presenting a formidable challenge for native MS as a means of characterizing its interactions with both the host cell–surface receptor ACE2 and the drug candidates capable of disrupting this interaction. In this work, we evaluate the utility of native MS complemented with the experimental methods using gas-phase chemistry (limited charge reduction) to obtain meaningful information on the association of the S1 domain of the S-protein with the ACE2 ectodomain, and the influence of a small synthetic heparinoid on this interaction. Native MS reveals the presence of several different S1 oligomers in solution and allows the stoichiometry of the most prominent S1/ACE2 complexes to be determined. This enables meaningful interpretation of the changes in native MS that are observed upon addition of a small synthetic heparinoid (the pentasaccharide fondaparinux) to the S1/ACE2 solution, confirming that the small polyanion destabilizes the protein/receptor binding.
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