Reshaping Lipid Biochemistry by Pushing Barriers in Structural Lipidomics

Abstract

Lipidomics is a rapidly growing field with numerous examples showing the importance of lipid molecules throughout biology. It has also shed light onto the vast and complex functions performed by many lipids that possess an immense diversity in molecular structures. Mass spectrometry (MS) is the tool of choice for analyzing lipids and has been the key catalyst driving the field forward. However, MS does not yet permit true molecular lipidomics wherein the identification and quantification of lipids having defined molecular structures can be routinely achieved. Here we describe recent advances in MS‐based lipidomics that allow access to higher levels of molecular information in lipidomics experiments. These advances will form a key piece of the puzzle as the field moves towards systems characterization of lipids at the molecular level.

Rapid Identification of Ischemic Injury in Renal Tissue by Mass-Spectrometry Imaging

“…29−33 Although much more is known about the PLA2 family of enzymes, the differentiation of PLA1- and PLA2-driven hydrolysis is not generally possible using MSI or indeed conventional MS-based lipidomics. 34 MSI typically lacks the isomeric specificity required to localize the sn positions of the acyl chains on both the precursor and the lyso-lipid products, which is essential for differentiating PLA1- and PLA2-based processes. Thus, our results likely reflect the cumulative effects of all PLA forms.…”

“…In particular, a suite of lysophospholipids have been identified as significantly elevated in severe ischemia compared with in mild ischemia. The source of these lysolipids is likely lipid degradation by increased activation of phospholipase A1 (PLA1) or A2 (PLA2) enzymes, with the latter in particular having been previously shown to exhibit elevated activation during ischemia. − Although much more is known about the PLA2 family of enzymes, the differentiation of PLA1- and PLA2-driven hydrolysis is not generally possible using MSI or indeed conventional MS-based lipidomics . MSI typically lacks the isomeric specificity required to localize the sn positions of the acyl chains on both the precursor and the lyso-lipid products, which is essential for differentiating PLA1- and PLA2-based processes.…”

Imaging and Analysis of Isomeric Unsaturated Lipids through Online Photochemical Derivatization of Carbon–Carbon Double Bonds**

“…Recent studies have attributed changes in the relative abundance of positional isomers to altered lipid metabolism in cancer [4, 5] and diabetes [6] . These findings inspire the development of new approaches for the identification of C=C bond locations in unsaturated lipids [7] …”

Integrating ion mobility and imaging mass spectrometry for comprehensive analysis of biological tissues: A brief review and perspective

“…The authors demonstrated effective analysis of caffeine and mobility separation of glucose and fructose when applied to analysis of Coca‐Cola®. This separation presents obvious advantages for use in imaging of small molecules, where MS/MS is often insufficient for isomer distinction, a situation that severely hampers analysis 140 . In contrast to previous work coupling IR‐MALDESI with trap‐based instruments, 141–144 this system provided the necessary dynamic range to detect intact proteins, lipids, and small molecules in an image of an oak leaf.…”