Structural Characterization and Quantitation of Ether-Linked Glycerophospholipids in Peroxisome Biogenesis Disorder Tissue by Ultraviolet Photodissociation Mass Spectrometry.
Structural Characterization and Quantitation of Ether-Linked Glycerophospholipids in Peroxisome Biogenesis Disorder Tissue by Ultraviolet Photodissociation Mass Spectrometry.
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DOI：
10.1021/acs.analchem.2c01274
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发表时间：
2022-09-20
影响因子：
7.4
通讯作者：
Brodbelt, Jennifer S.
中科院分区：
文献类型：
--
作者：
Blevins, Molly S.;Shields, Samuel W. J.;Cui, Wei;Fallatah, Wedad;Moser, Ann B.;Braverman, Nancy E.;Brodbelt, Jennifer S.
醚甘油磷脂（GP）在过氧化物酶体病症和其他疾病中的生物学影响使其成为诊断测定或解读病症病理学的生物标志物的重要靶标。醚脂质包括胞浆酰脂质和胞浆酰脂质两者，其各自分别在sn-1连接位置处含有醚键或乙烯基醚键。与传统的二酰基GP相比，这种连接排除了通过传统的基于碰撞的MS/MS技术通过质谱法对其进行详细表征。此外，醚脂质的plasmanyl和plasmenyl对的异构性质引入了进一步的复杂性水平，这阻碍了对这些物质的分析。在这里，我们利用213 nm的紫外光解离质谱（UVPD-MS）的磷脂酰乙醇胺（PE）和磷脂酰胆碱（PC）plasmenyl和plasmanyl脂质在小鼠脑组织中的详细表征。213 nm UVPD-MS首次成功区分了这四种醚脂质亚型。我们将这种UVPD-MS方法与反相液相色谱（RPLC）结合，用于表征和相对定量来自正常和患病（Pex 7缺陷模型过氧化物酶体生物发生障碍，RCDP）小鼠脑组织的醚脂质，突出了确定醚脂质的特定结构特征的能力，这些特征对于监测过氧化物酶体障碍中的异常脂质代谢非常重要。
The biological impact of ether glycerophospholipids (GP) in peroxisomal disorders and other diseases makes them significant targets as biomarkers for diagnostic assays or deciphering pathology of the disorders. Ether lipids include both plasmanyl and plasmenyl lipids, which each contain an ether or a vinyl ether bond at the sn-1 linkage position, respectively. This linkage, in contrast to traditional diacyl GPs, precludes their detailed characterization by mass spectrometry via traditional collisional-based MS/MS techniques. Additionally, the isomeric nature of plasmanyl and plasmenyl pairs of ether lipids introduces a further level of complexity that impedes analysis of these species. Here, we utilize 213 nm ultraviolet photodissociation mass spectrometry (UVPD-MS) for detailed characterization of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) plasmenyl and plasmanyl lipids in mouse brain tissue. 213 nm UVPD-MS enables the successful differentiation of these four ether lipid subtypes for the first time. We couple this UVPD-MS methodology to reversed-phase liquid chromatography (RPLC) for characterization and relative quantitation of ether lipids from normal and diseased (Pex7 deficiency modeling the peroxisome biogenesis disorder, RCDP) mouse brain tissue, highlighting the ability to pinpoint specific structural features of ether lipids that are important for monitoring aberrant lipid metabolism in peroxisomal disorders.
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