Characterization of Phosphatidylcholine Oxidation Products by MALDI MSn
Characterization of Phosphatidylcholine Oxidation Products by MALDI MSn
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DOI：
10.1021/ac402400f
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发表时间：
2013-12-03
影响因子：
7.4
通讯作者：
Yost, Richard A.
中科院分区：
文献类型：
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作者：
Stutts, Whitney L.;Menger, Robert F.;Yost, Richard A.
磷脂氧化与许多与年龄相关的疾病和神经退行性疾病的发病机制和进展有关。尽管有这些影响，这一大类生物分子的特征仍然很少。在这项工作中，完整磷脂酰胆碱氧化产物 (OxPC) 的 [M + H](+) 和 [M + Na](+) 离子的碎片模式通过基质辅助激光解吸/电离串联质谱 (MALDI MSn, n = 2、3 和 4) 进行了表征。短链 OxPC 的 [M + H](+) 和 [M + Na](+) 离子的 MS' 产生与 PC 头基和脂肪酸取代基相关的产物离子。 [M + Na - N(CH3)(3)](+) 离子的 MS3 产生碎片，表明 OxPC 修饰；具体来说，对于含有末端羧酸而不是醛的 OxPC，观察到对应于 CO2 中性损失（NL 为 44）的产物离子。此外，[M + Na - HPO4(CH2)(2)N(CH3)(3)](+) 离子的 MS4 导致依赖于 sn-2 脂肪酸链长度和官能团类型的断裂途径。具体来说，含有 CHO 的 OxPC 与棕榈酸酯化到甘油主链的 sn-1 位置，产生的 NL 为 254，比棕榈酸的标称质量低 2 u，而类似的末端含有 COOH 的 OxPC 则表现出 NL 为 256。最后，相对于末端羧基的 γ-酮的存在导致沿 sn-2 取代基的 C-C 键断裂，从而提供了诊断性含酮 OxPC 的产物离子。这项工作说明了 MSn 在线性离子阱上提供的增强选择性，并开发了一种鉴定 PC 氧化的各个产物的方法。
Phospholipid oxidation has been implicated in the pathogenesis and progression of numerous age-related and neurodegenerative diseases. Despite these implications, this broad class of biomolecules remains poorly characterized. In this work, the fragmentation patterns of [M + H](+) and [M + Na](+) ions of intact phosphatidylcholine oxidation products (OxPCs) were characterized by matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI MSn, n = 2, 3, and 4). MS' of both the [M + H](+) and [M + Na](+) ions of short-chain OxPCs yielded product ions related to the PC headgroup and the fatty acid substituents. MS3 of the [M + Na - N(CH3)(3)](+) ions yielded fragmentation indicative of the OxPC modification; specifically, a product ion corresponding to the neutral loss of CO2 (NL of 44) was observed for OxPCs containing a terminal carboxylic acid rather than an aldehyde. Furthermore, MS4 of the [M + Na - HPO4(CH2)(2)N(CH3)(3)](+) ions resulted in fragmentation pathways dependent on the sn-2 fatty acid chain length and type of functional group(s). Specifically, CHO-containing OxPCs with palmitic acid esterified to the sn-1 position of the glycerol backbone yielded a NL of 254, 2 u less than the nominal mass of palmitic acid, whereas the analogous terminal COOH-containing OxPCs demonstrated a NL of 256. Finally, the presence of a gamma-ketone relative to the terminal carboxyl group resulted in C-C bond cleavages along the sn-2 substituent, providing diagnostic product ions for keto-containing OxPCs. This work illustrates the enhanced selectivity afforded by MSn on the linear ion trap and develops a method for the identification of individual products of PC oxidation.