Abstract:In mammalian systems “sterolomics” can be regarded as the quantitative or semi-quantitative profiling of all metabolites derived from cholesterol and its cyclic precursors. The system can be further complicated by metabolites derived from ingested phytosterols or pharmaceuticals, but this is beyond the scope of this article. “Sterolomics” can be performed on either an unbiased global format, or more usually, exploiting a targeted format. Here we discuss the different mass spectrometry-based analytical techniqu… Show more
“…To better understand the involvement of 7KC in the pathophysiology of COVID-19, rapid and easy to use analytical tests are a necessity. These could include ELISA tests using anti-7KC mouse monoclonal antibodies [ 88 ] or dried blood tests [ 89 ] associated with gas chromatography or liquid chromatography coupled with mass spectrometry allowing the simultaneous identification and quantification of several oxysterols and of their metabolites [ 90 , 24 ]. Fig.…”
Section: Potential Role Of 7-ketocholesterol In the Pathophysiology Of Covid-19mentioning
“…To better understand the involvement of 7KC in the pathophysiology of COVID-19, rapid and easy to use analytical tests are a necessity. These could include ELISA tests using anti-7KC mouse monoclonal antibodies [ 88 ] or dried blood tests [ 89 ] associated with gas chromatography or liquid chromatography coupled with mass spectrometry allowing the simultaneous identification and quantification of several oxysterols and of their metabolites [ 90 , 24 ]. Fig.…”
Section: Potential Role Of 7-ketocholesterol In the Pathophysiology Of Covid-19mentioning
“…To reach this goal, indissociable efforts of investigating and validating accurate gene functions in dedicated heterologous expression systems will further support advanced phylogenomic studies ( Desmond and Gribaldo, 2009 ; Gold et al, 2016 ). In the same vein, progresses in sterolomics will in turn provide users with powerful methods to envisage large-scale metaphenomics for a data-driven treatment of biological questions ( Griffiths and Wang, 2019 ). Nonetheless, yet unknown genes and enzymes may well arise from forward and serendipitous genetic screenings.…”
The remarkable diversity of sterol biosynthetic capacities described in living organisms is enriched at a fast pace by a growing number of sequenced genomes. Whereas analytical chemistry has produced a wealth of sterol profiles of species in diverse taxonomic groups including seed and non-seed plants, algae, phytoplanktonic species and other unicellular eukaryotes, functional assays and validation of candidate genes unveils new enzymes and new pathways besides canonical biosynthetic schemes. An overview of the current landscape of sterol pathways in the tree of life is tentatively assembled in a series of sterolotypes that encompass major groups and provides also peculiar features of sterol profiles in bacteria, fungi, plants, and algae.
“…1C [65,67]). However, they are not ideal biomarkers since they lack specificity and can be produced by ex vivo cholesterol oxidation, generating misleading results [133,134]. 7-KC in particular is highly important in CVD and aging due to its cytotoxicity [133].…”
Section: Oxygenated Lipids As Potential Biomarkersmentioning
Great advances in lipidomics during the last years have opened the door to a broader knowledge of oxygenated lipids. These substances are derived either from the inclusion of previously hydroxylated fatty acids in the lipid structure of sphingolipids and acyl-L-carnitines, or by enzymatic and nonenzymatic modifications (oxidized lipids) of glycerophospholipids (including cardiolipins), cholesteryl esters and cholesterol. Despite their significance in the regulation of multiple diseases such as cancer or diabetes, the number of experimentally detected oxygenated lipids remains relatively low. This is in part due to the main challenges in their analysis, which are their low natural concentrations, their wide diversity of physicochemical properties, presence of isomers, and their a priori unknown presence in the biological samples. In particular, analysis of oxidized lipids, especially peroxides, has become a daunting task in liquid chromatography coupled to mass spectrometry (LC-MS) due to their high chemical and thermal instability, and the potential for further propagation of lipid oxidation and eventual degradation. The aim of this review is to highlight the experimental conditions on sample preparation procedures, the LC-MS based analytical approaches for identification and quantification of oxygenated lipids, and their relation as potential biomarkers in diseases based on the most relevant articles published in the last five years. Regarding sample preparation, special attention has been given to antioxidants, internal standards, extraction and concentration methods, and derivatization approaches. Moreover, targeted, semi-targeted and non-targeted strategies have been discussed presenting examples. Finally, considerations on the structural identification, one of the main challenges, are presented.
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