School of Chemistry and Physics, Queensland University of Technology, Brisbane, Queensland, Australia; Central Analytical Research Facility (CARF), Queensland University of Technology, Brisbane, Queensland, Australia.
The Maastricht MultiModal Molecular Imaging Institute (M4I), Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, The Netherlands.
J Lipid Res. 2022 Jun;63(6):100223. doi: 10.1016/j.jlr.2022.100223. Epub 2022 May 7.
The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics.
癌细胞的细胞能量和生物量需求在细胞外 FAs 的摄取与其从头合成之间产生了复杂的动态关系。鉴于从头合成的 FAs 氧化产生净能量损失，这意味着这两个来源的 FAs 必须具有不同的代谢命运；然而，迄今为止，所有的 FAs 都被认为是一个共同池的一部分。为了探究细胞 FAs 潜在的代谢分区，向癌细胞中补充了稳定同位素标记的 FAs。对生成的甘油磷脂的结构分析表明，来自摄取的标记 FAs 主要被整合到甘油主链的规范（sn-）位置上。令人惊讶的是，标记的 FA 摄取还破坏了未标记脂质组的规范异构体模式，并将 n-3 和 n-6 PUFA 重新分配到甘油磷脂类别中。这些结构变化支持了来源于摄取或从头合成来源的 FAs 在代谢命运上存在差异，并证明了通常隐藏在常规脂质组学中的独特信号转导和重塑行为。
