Biran Assaf, Santos Tania C B, Dingjan Tamir, Futerman Anthony H
Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Biochim Biophys Acta Mol Cell Biol Lipids. 2024 Apr;1869(3):159462. doi: 10.1016/j.bbalip.2024.159462. Epub 2024 Feb 1.
In eukaryotes, the de novo synthesis of sphingolipids (SLs) consists of multiple sequential steps which are compartmentalized between the endoplasmic reticulum and the Golgi apparatus. Studies over many decades have identified the enzymes in the pathway, their localization, topology and an array of regulatory mechanisms. However, little is known about the evolutionary forces that underly the generation of this complex pathway or of its anteome, i.e., the metabolic pathways that converge on the SL biosynthetic pathway and are essential for its activity. After briefly describing the pathway, we discuss the mechanisms by which the enzymes of the SL biosynthetic pathway are targeted to their different subcellular locations, how the pathway per se may have evolved, including its compartmentalization, and the relationship of the pathway to eukaryogenesis. We discuss the circular interdependence of the evolution of the SL pathway, and comment on whether current Darwinian evolutionary models are able to provide genuine mechanistic insight into how the pathway came into being.
在真核生物中，鞘脂（SLs）的从头合成由多个连续步骤组成，这些步骤在内质网和高尔基体之间进行区室化。几十年来的研究已经确定了该途径中的酶、它们的定位、拓扑结构以及一系列调控机制。然而，对于构成这一复杂途径及其前体组（即汇聚到鞘脂生物合成途径并对其活性至关重要的代谢途径）的进化驱动力，我们知之甚少。在简要描述该途径之后，我们将讨论鞘脂生物合成途径中的酶靶向其不同亚细胞位置的机制、该途径本身可能的进化方式（包括其区室化）以及该途径与真核生物起源的关系。我们将讨论鞘脂途径进化的循环相互依存关系，并评论当前的达尔文进化模型是否能够真正深入地从机制上解释该途径是如何形成的。
