Metabolic labeling, in which substrate analogs containing diminutive tags can infiltrate biosynthetic pathways and generate labeled products in cells, has led to dramatic advancements in the means by which complex biomolecules can be detected and biological processes can be elucidated. Within this realm, metabolic labeling of lipid products, particularly in a manner that is headgroup-specific, brings about a number of technical challenges including the complexity of lipid metabolic pathways as well as the simplicity of biosynthetic precursors to headgroup functionality. As such, only a handful of strategies for metabolic labeling of lipids have thus far been reported. However, these approaches provide enticing examples of how strategic modifications to substrate structures, particularly by introducing clickable moieties, can enable the hijacking of lipid biosynthesis. Furthermore, early work in this field has led to an explosion in diverse applications by which these techniques have been exploited to answer key biological questions or detect and track various lipid-containing biological entities. In this article, we review these efforts and emphasize recent advancements in the development and application of lipid metabolic labeling strategies.

代谢标记，其中含有小型标签的底物类似物可以渗透生物合成途径并在细胞中产生标记产物，这使得检测复杂生物分子和阐明生物过程的方法取得了巨大进步。在这个领域中，脂质产品的代谢标记，特别是以头基特异性的方式，带来了许多技术挑战，包括脂质代谢途径的复杂性以及头基功能的生物合成前体的简单性。因此，迄今为止仅报道了少数脂质代谢标记策略。然而，这些方法提供了诱人的例子，说明如何对底物结构进行策略性修饰，特别是通过引入可点击部分，能够劫持脂质生物合成。此外，该领域的早期工作导致了各种应用的爆炸式增长，这些技术已被用来回答关键的生物学问题或检测和跟踪各种含脂质的生物实体。在本文中，我们回顾了这些努力，并强调了脂质代谢标记策略的开发和应用的最新进展。