In the middle of the 1960s, I began graduate school and at the same time started on the path of using mass spectrometry to gain insight into various aspects of lipid biochemistry. This was not a straight path but one that went from organic geochemistry, to lunar sample analysis, to a pursuit of the structure of an elusive and very active, lipid mediator slow reacting substance of anaphylaxis (SRS-A). The discovery of the structure of SRS-A opened important questions about phospholipid biochemistry and the arachidonate cycle in cells. I have written this reflection to highlight the various advances in mass spectrometry that occurred during this time that had a great impact on our ability to study lipid biochemistry. I specifically applied these new advances to studies of leukotriene biosynthesis in vivo, leukotriene metabolism, and arachidonate-containing phospholipids that are essential in providing arachidonic acid for the 5-lipoxygenase pathway. Along the way imaging mass spectrometry was shown to be a powerful tool to probe lipids as they exist in tissue slices. We found this as just one of the ways to use the emerging technology of lipidomics to study human pathophysiology. Our studies of neutral lipids and oxidized phospholipids were especially challenging due to the total number of molecular species that could be found in cells. Many challenges remain in using mass spectrometry for lipid studies and a few are presented.

中文翻译：

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脂质质谱法：走了50年之路。

1960年代中期，我开始读研究生，并同时开始使用质谱法深入了解脂质生物化学的各个方面。这不是一条直路，而是一条从有机地球化学到月球样品分析，再到追求一种难以捉摸的，非常活跃的，脂质介导的过敏反应慢反应物质（SRS-A）的结构。SRS-A结构的发现打开了有关磷脂生物化学和细胞中花生四烯酸循环的重要问题。我写了这篇反思来强调这段时间发生的质谱学的各种进步，这些进步对我们研究脂质生物化学的能力产生了重大影响。我将这些新进展专门用于体内白三烯生物合成，白三烯代谢，以及含有花生四烯酸酯的磷脂，这些磷脂对于为5-脂氧合酶途径提供花生四烯酸是必不可少的。沿途显示，质谱成像是探测组织切片中存在的脂质的强大工具。我们发现这只是使用脂质组学新兴技术研究人类病理生理学的方法之一。由于对细胞中可能存在的分子种类总数的研究，我们对中性脂质和氧化磷脂的研究尤其具有挑战性。使用质谱进行脂质研究仍然存在许多挑战，并提出了一些挑战。我们发现这只是使用脂质组学新兴技术研究人类病理生理学的方法之一。由于对细胞中可能存在的分子种类总数的研究，我们对中性脂质和氧化磷脂的研究尤其具有挑战性。使用质谱进行脂质研究仍然存在许多挑战，并提出了一些挑战。我们发现这只是使用脂质组学新兴技术研究人类病理生理学的方法之一。由于对细胞中可能存在的分子种类总数的研究，我们对中性脂质和氧化磷脂的研究尤其具有挑战性。使用质谱进行脂质研究仍然存在许多挑战，并提出了一些挑战。