Department of Biomolecular Sciences, Weizmann Institute of Science, 7610001, Rehovot, Israel.
Pflugers Arch. 2024 Dec;476(12):1781-1788. doi: 10.1007/s00424-024-03020-0. Epub 2024 Sep 19.
Research on sphingolipids has proliferated exponentially over the past couple of decades, as exemplified in the findings reported at the International Leopoldina Symposium on Lipid Signaling held in Frankfurt in late 2023. Most researchers in the field study how sphingolipids function in regulating a variety of cellular processes and, in particular, how they are dysregulated in numerous human diseases; however, I now propose that we implement a more holistic research program in our study of sphingolipids, which embraces a sense of awe and wonder at the complexities and beauty of sphingolipids and of sphingolipid metabolism. I will outline the chemical complexity of sphingolipids, their modes of interaction within the lipid bilayer, and their biosynthetic pathways. I will then briefly touch upon the ability of current neo-Darwinian mechanisms to explain the emergence of both sphingolipids and of the complex pathways that generate them. Although such discussion is normally considered taboo in biological circles, I nevertheless submit that in-depth analysis of the minutiae of metabolic pathways, such as those of the sphingolipid biosynthetic pathway, raises challenges to current neo-Darwinian mechanisms that should not be shunned or ignored.
在过去的几十年中,人们对神经鞘脂的研究呈指数级增长,这一点在 2023 年末于法兰克福举行的国际利奥波第纳学会脂质信号研讨会上的报告中得到了体现。该领域的大多数研究人员都在研究神经鞘脂在调节各种细胞过程中的作用,特别是它们在许多人类疾病中的失调情况;然而,我现在提议,我们在研究神经鞘脂时实施一个更加全面的研究计划,这个计划包括对神经鞘脂及其代谢的复杂性和美妙感到敬畏和惊奇。我将概述神经鞘脂的化学复杂性、它们在脂质双层中的相互作用方式以及它们的生物合成途径。然后,我将简要讨论当前新达尔文主义机制解释神经鞘脂及其生成它们的复杂途径的出现的能力。虽然这样的讨论在生物学界通常被视为禁忌,但我仍然认为,对代谢途径(如神经鞘脂生物合成途径)的细节进行深入分析,对当前的新达尔文主义机制提出了不应回避或忽视的挑战。