Institute of Protein Biochemistry, National Research Council of Italy, Naples, Italy.
Institute of Protein Biochemistry, National Research Council of Italy, Naples, Italy; Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Chem Phys Lipids. 2019 Jan;218:103-111. doi: 10.1016/j.chemphyslip.2018.11.003. Epub 2018 Nov 23.
Biosynthetic pathways play a fundamental role in the building and operation of the cell by synthesizing the constituents by which the cell is constructed, and by producing signalling intermediates that play a key role in cell regulation. While a lot is known about the metabolite profile of the cells and about the biochemical pathways through which these metabolites are produced, the cellular localization of the biosynthetic machineries and the importance of this localization to the regulation of the metabolism has often been given less attention. This derives from the fact that, for several of these pathways, the enzymes involved are found colocalized in one compartment where their specific localization is unlikely to influence their function. The sphingolipid (SL) metabolic pathway is a notable exception to this as SL synthetic enzymes are laid out on a specific pattern across the secretory compartments. Such compartmentalized organization of the SL synthesis has functional implications as it makes the fine-tuned regulation of the process possible by allowing cells to regulate specific segments of the pathway in response to stimuli and for adaptation. The organization, dynamics, and regulation of the SLs and their biosynthetic machinery have been investigated using imaging-based methods. Here we provide a brief introduction to the techniques that have been or that could be employed to visualize the SL biosynthetic machinery and SLs themselves and discuss the insights provided by these studies in understanding this metabolism.
生物合成途径通过合成细胞构建所需的成分以及产生在细胞调节中起关键作用的信号中间体，在细胞的构建和运作中起着基础性作用。尽管人们对细胞的代谢物谱以及这些代谢物产生的生化途径有了很多了解，但生物合成机制在细胞中的定位及其对代谢调节的重要性往往没有得到太多关注。这是因为对于其中的一些途径，所涉及的酶在一个隔室中被发现是共定位的，在这个隔室中，它们的特定定位不太可能影响它们的功能。鞘脂（SL）代谢途径是一个明显的例外，因为 SL 合成酶在分泌隔室中按照特定的模式排列。这种 SL 合成的隔室化组织具有功能意义，因为它可以使细胞能够根据刺激和适应来调节途径的特定片段，从而实现对该过程的精细调节。已经使用基于成像的方法研究了 SL 及其生物合成机制的组织、动态和调节。在这里，我们简要介绍了已经或可能用于可视化 SL 生物合成机制和 SL 本身的技术，并讨论了这些研究在理解这种代谢方面提供的见解。
