Sn‐1 Specificity of Lysophosphatidylcholine Acyltransferase‐1 Revealed by a Mass Spectrometry‐Based Assay. (28th December 2022)

• Record Type: Journal Article
• Authors: Zhao, Xue; Liang, Jiaqi; Chen, Ziye; Jian, Ruijun; Qian, Yao; Wang, Yunfang; Guo, Zhiying; Zhang, Wenpeng; Zhang, Ying; Yin, Hang; Xia, Yu
• Is Part Of: Angewandte Chemie. Volume 135:Number 6(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-28
• Subjects: Desorption Electrospray Ionization -- Lipid Isomer -- Lysophosphatidylcholine Acyltransferase-1 -- Tandem Mass Spectrometry -- Tissue Imaging; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202215556
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Lysophosphatidylcholine acyltransferase‐1 (LPCAT1) plays a critical role in the remodeling of phosphatidylcholines (PCs) in cellular lipidome. However, evidence is scarce regarding its sn ‐selectivity, viz. the preference of assembling acyl‐Coenzyme A (CoA) at the C1 or C2‐hydroxyl on a glycerol backbone because of difficulty to quantify the thus‐formed PC sn ‐isomers. We have established a multiplexed assay to measure both sn ‐ and acyl‐chain selectivity of LPCAT1 toward a mixture of acyl‐CoAs by integrating isomer‐resolving tandem mass spectrometry. Our findings reveal that LPCAT1 shows exclusive sn ‐1 specificity regardless of the identity of acyl‐CoAs. We further confirm that elevated PC 18 : 1/16:0 relative to its sn ‐isomer results from an increased expression of LPCAT1 in human hepatocellular carcinoma (HCC) tissue as compared to normal liver tissue. MS imaging via desorption electrospray ionization of PC 18 : 1/16:0 thus enables visualization of HCC margins in human liver tissue at a molecular level. Abstract : An isomer‐resolving mass spectrometry assay reveals that lysophosphatidylcholine acyltransferase‐1 (LPCAT1) has an sn ‐1 specificity when catalyzing the synthesis of phosphatidylcholines (PCs). The specific link between PC 18 : 1/16:0 and the activity of LPCAT1 enables visualization of the boundaries between cancerous and normal regions in human hepatocellular carcinoma (HCC) tissue via desorption electrospray ionization (DESI).