Coupling the Paternò-Büchi (PB) Reaction With Mass Spectrometry to Study Unsaturated Fatty Acids in Mouse Model of Multiple Sclerosis

Abstract

Lipid dysregulation has been implicated in multiple sclerosis due to its involvement during and after inflammation. In this study, we have profiled fatty acids (FAs) in the mouse model of multiple sclerosis with new capabilities of assigning carbon-carbon double bond (C=C) location(s) and quantifying C=C location isomers. These new capabilities are enabled by pairing the solution phase Paternò-Büchi (PB) reaction that modifies C=C bonds in FAs, with tandem mass spectrometry (MS/MS), termed as PB-MS/MS. A series of unsaturated FAs and C=C location isomers have been identified, including FA17:1 (Δ10), FA18:1 (Δ9 and Δ11), FA18:2 (Δ9 and Δ12), and FA 20:4 (Δ5, Δ8, Δ11, Δ14). Notable differences in saturated and unsaturated FAs between normal and experimental autoimmune encephalomyelitis (EAE) mice spinal cords have been detected. Furthermore, the effects of hydralazine, a scavenger of acrolein, on profile changes of FAs in mice were studied. Increased Δ11-to-Δ9 isomer ratios for FA 18:1 were noted in the diseased samples as compared to the control. The present work provides a facile and robust analytical method for the quantitation of unsaturated FAs as well as identification of FA C=C location isomers, which will facilitate discovering prospective lipid markers in multiple sclerosis.

Metabolomics and complementary techniques to investigate the plant phytochemical cosmos

“…In addition to classic ozone-induced dissociation (OzID), 265 which requires prolonged reaction time for fragmentation, the Paterno-Buchi (PB) reaction is used to determine the position of the double bonds in free fatty acids and complex lipids, such as glycero(phospho)lipids. 266,267 Following the lipid double bond reaction with acetone or 2-acetylpyridine under UV irradiation, the produced oxetane (four-membered ring ether) moiety is preferentially fragmented by low-energy CID. Combined with 2-acetylpyridine and MS n analysis, the PB reaction can be used to determine the double bond positions and snpositional isomers.…”

Review of Recent Advances in Lipid Analysis of Biological Samples via Ambient Ionization Mass Spectrometry

“…The PB reaction is a classic [2 + 2] photochemical reaction and is widely used for the formation of oxetane ring compounds in organic synthesis [41]. The PB reaction has gained attention for lipid structural elucidation, since its coupling to tandem MS (PB-MS/MS) analysis can result in C=C positional information in unsaturated lipids [42,43]. To clearly describe the reaction mechanism of the PB reaction with the C=C bond, acetone as a PB reagent is taken as an example.…”

Unraveling the Double Bond Position of Fatty Acids by GC-MS Using Electron Capture APCI and In-Source Fragmentation Patterns

“…For instance, the ratio of ω-3 to ω-6 FAs plays an important role in nutrition. Excess consumption of ω-6 FAs has been linked to various mental illnesses such as depression, severe mood swings, bipolar disorder, and attention-deficit/hyperactivity disorder (ADHD). , Moreover, the ratio of regioisomeric FAs might also serve as an indicator of multiple sclerosis or cancer. , Thereby, analytical strategies are necessary to identify and determine the FA regioisomers. However, their close structural similarities complicate the chromatographic separation, leading to coelutions of the regioisomers and making the identification of the double bond position challenging …”