sn-Position-Resolved Quantification of Aminophospholipids by Isotopic N,N-Dimethyl Leucine Labeling and High-Resolution Ion Mobility Mass Spectrometry

被引：0
|
作者：
Xu, Shuling [1 ]
Zhu, Zhijun [2 ]
Gu, Ting-Jia [1 ]
Wang, Zicong [1 ]
Delafield, Daniel G. [2 ]
Rigby, Michael J. [3 ,4 ,5 ]
Lu, Gaoyuan [1 ]
Ma, Min [1 ]
Liu, Peng-Kai [6 ]
Puglielli, Luigi [3 ,4 ,7 ]
Li, Lingjun [1 ,2 ,6 ,8 ,9 ]
机构：
[1] School of Pharmacy, University of Wisconsin-Madison, Madison,WI,53705, United States
[2] Department of Chemistry, University of Wisconsin-Madison, Madison,WI,53706, United States
[3] Department of Medicine, University of Wisconsin-Madison, Madison,WI,53705, United States
[4] Waisman Center, University of Wisconsin-Madison, Madison,WI,53705, United States
[5] Neuroscience Training Program, University of Wisconsin-Madison, Madison,WI,53705, United States
[6] Biophysics Program, University of Wisconsin-Madison, Madison,WI,53705, United States
[7] Geriatric Research Education Clinical Center, Veterans Affairs Medical Center, Madison,WI,53705, United States
[8] Lachman Institute for Pharmaceutical Development, School of Pharmacy, University of Wisconsin-Madison, Madison,WI,53705, United States
[9] Wisconsin Center for NanoBioSystems, School of Pharmacy, University of Wisconsin-Madison, Madison,WI,53705, United States
来源：
Analytical Chemistry | 2024年 / 96卷 / 50期
关键词：
Aminophospholipids; (APLs); composed of phosphatidylethanolamines (PEs) and phosphatidylserines (PSs); are vital components of mammalian cell membranes and lipoproteins; participating in both homeostasis and cellular signaling. Their structural changes; including the permutation of fatty acid connectivity (sn-positions); due to dysfunctional metabolic processes have been linked to many diseases. However; the accurate quantification of APLs with unambiguous fatty acyl assignment through routine label-free LC-MS/MS lipidomic analysis remains a major challenge. In this study; we explore the functionalization of the free primary amine groups of APLs using amine-reactive isotopic N; N-dimethyl leucine (iDiLeu) and employ high-resolution ion mobility MS (IM-MS) to develop a novel method for sensitive discernment and accurate quantification of APL sn-isomers. With high-resolution demultiplexing (HRdm) providing IM resolving power >200; labeled sn-isomeric pairs of APLs (ΔCCS ≈ 1%) demonstrate excellent; near baseline separation. In addition to greatly enhanced sensitivity; 5-plex iDiLeu labeling enables the construction of an internal 4-point calibration curve and therefore absolute quantification of APL sn-isomers in a single run. This strategy enabled precise annotation and quantification of 239 APLs including 60 pairs of sn-isomers in the mouse cortex. Additionally; we were able to find ratio changes in multiple APL sn-isomer pairs between wild type and APP/PS1 Alzheimer’s disease (AD) model mice at different ages; indicating their strong correlation to AD progression. This strategy could provide universal utility in unraveling the alteration of APL sn-isomers; which have long been considered as the dark matter of traditional lipidomic analyses; leading to more precise elucidation of molecular mechanisms of various diseases. © 2024 American Chemical Society;
D O I：
10.1021/acs.analchem.4c05107
中图分类号：
学科分类号：
摘要：
引用
收藏
页码：20098 / 20106
相关论文
共 16 条
  • [1] High-Resolution Enabled 5-plex Mass Defect-Based N,N-Dimethyl Leucine Tags for Quantitative Proteomics
    Zhong, Xiaofang
    Frost, Dustin C.
    Li, Lingjun
    [J]. ANALYTICAL CHEMISTRY, 2019, 91 (13) : 7991 - 7995
  • [2] Detection and Quantification of Psychoactive N,N-Dimethyltryptamine in Ayahuasca Brews by Ambient Ionization High-Resolution Mass Spectrometry
    Chambers, Megan, I
    Appley, Meghan G.
    Longo, Cameron M.
    Musah, Rabi A.
    [J]. ACS OMEGA, 2020, 5 (44): : 28547 - 28554
  • [3] Development and application of a dual isotopic labeling method for enhanced detection and quantification of stimulants in urine samples using high-resolution mass spectrometry
    Wang, Yang
    Li, Wanli
    Deng, Xiaojun
    [J]. Analytical and Bioanalytical Chemistry, 2024, 416 (29) : 7073 - 7084
  • [4] Application of Safirinium N-Hydroxysuccinimide Esters to Derivatization of Peptides for High-Resolution Mass Spectrometry, Tandem Mass Spectrometry, and Fluorescent Labeling of Bacterial Cells
    Fedorowicz, Joanna
    Wierzbicka, Magdalena
    Cebrat, Marek
    Wisniewska, Paulina
    Piatek, Rafal
    Zalewska-Piatek, Beata
    Szewczuk, Zbigniew
    Saczewski, Jaroslaw
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (24) : 1 - 27
  • [5] LC-quadrupole/Orbitrap high-resolution mass spectrometry enables stable isotope-resolved simultaneous quantification and 13C-isotopic labeling of acyl-coenzyme A thioesters
    Alexander J. Frey
    Daniel R. Feldman
    Sophie Trefely
    Andrew J. Worth
    Sankha S. Basu
    Nathaniel W. Snyder
    [J]. Analytical and Bioanalytical Chemistry, 2016, 408 : 3651 - 3658
  • [6] LC-quadrupole/Orbitrap high-resolution mass spectrometry enables stable isotope-resolved simultaneous quantification and 13C-isotopic labeling of acyl-coenzyme A thioesters
    Frey, Alexander J.
    Feldman, Daniel R.
    Trefely, Sophie
    Worth, Andrew J.
    Basu, Sankha S.
    Snyder, Nathaniel W.
    [J]. ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 2016, 408 (13) : 3651 - 3658
  • [7] N-Glycosylation profiling of intact target proteins by high-resolution mass spectrometry (MS) and glycan analysis using ion mobility-MS/MS
    Quaranta, Alessandro
    Spasova, Maya
    Passarini, Elena
    Karlsson, Isabella
    Ndreu, Lorena
    Thorsen, Gunnar
    Ilag, Leopold L.
    [J]. ANALYST, 2020, 145 (05) : 1737 - 1748
  • [8] Spatially and temporally probing distinctive glycerophospholipid alterations in Alzheimer's disease mouse brain via high-resolution ion mobility-enabled sn-position resolved lipidomics
    Xu, Shuling
    Zhu, Zhijun
    Delafield, Daniel G.
    Rigby, Michael J.
    Lu, Gaoyuan
    Braun, Megan
    Puglielli, Luigi
    Li, Lingjun
    [J]. NATURE COMMUNICATIONS, 2024, 15 (01)
  • [9] Annotation and quantification of N-acyl homoserine lactones implied in bacterial quorum sensing by supercritical-fluid chromatography coupled with high-resolution mass spectrometry
    Thi Phuong Thuy Hoang
    Barthelemy, Morgane
    Lami, Raphael
    Stien, Didier
    Eparvier, Veronique
    Touboul, David
    [J]. ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 2020, 412 (10) : 2261 - 2276
  • [10] Annotation and quantification of N-acyl homoserine lactones implied in bacterial quorum sensing by supercritical-fluid chromatography coupled with high-resolution mass spectrometry
    Thi Phuong Thuy Hoang
    Morgane Barthélemy
    Raphaël Lami
    Didier Stien
    Véronique Eparvier
    David Touboul
    [J]. Analytical and Bioanalytical Chemistry, 2020, 412 : 2261 - 2276
12