Comprehensive Profiling of Amine-Containing Metabolite Isomers with Chiral Phosphorus Reagents

Xingxing Liu, Yifan Wu, Lei Guo, Xiaoyu Wang, Changkai Shan, Yaru Liu, Hanxiang An, Xinmei Kang, Rong Ding, Zongwei Cai, Jiyang Dong*, Yufen Zhao*, Xiang Gao*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

Abstract

Metabolite isomers play diverse and crucial roles in various metabolic processes. However, in untargeted metabolomics analysis, it remains a great challenge to distinguish between the constitutional isomers and enantiomers of amine-containing metabolites due to their similar chemical structures and physicochemical properties. In this work, the triplex stable isotope N-phosphoryl amino acids labeling (SIPAL) is developed to identify and relatively quantify the amine-containing metabolites and their isomers by using chiral phosphorus reagents coupled with high-resolution tandem mass spectroscopy. The constitutional isomers could be effectively distinguished with stereo isomers by using the diagnosis ions in MS/MS spectra. The in-house software MS-Isomerism has been parallelly developed for high-throughput screening and quantification. The proposed strategy enables the unbiased detection and relative quantification of isomers of amine-containing metabolites. Based on the characteristic triplet peaks with SIPAL tags, a total of 854 feature peaks with 154 isomer groups are successfully recognized as amine-containing metabolites in liver cells, in which 37 amine-containing metabolites, including amino acids, polyamines, and small peptides, are found to be significantly different between liver cancer cells and normal cells. Notably, it is the first time to identify S-acetyl-glutathione as an endogenous metabolite in liver cells. The SIPAL strategy could provide spectacular insight into the chemical structures and biological functions of the fascinating amine-containing metabolite isomers. The feasibility of SIPAL in isomeric metabolomics analysis may reach a deeper understanding of the mirror-chemistry in life and further advance the discovery of novel biomarkers for disease diagnosis.

Original languageEnglish
Pages (from-to)16830-16839
Number of pages10
JournalAnalytical Chemistry
Volume95
Issue number46
Early online date9 Nov 2023
DOIs
Publication statusPublished - 21 Nov 2023

Scopus Subject Areas

  • Analytical Chemistry

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