Santos Tania C B, Dingjan Tamir, Futerman Anthony H
Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
FEBS Lett. 2022 Sep;596(18):2345-2363. doi: 10.1002/1873-3468.14457. Epub 2022 Aug 4.
Modern cell membranes contain a bewildering complexity of lipids, among them sphingolipids (SLs). Advances in mass spectrometry have led to the realization that the number and combinatorial complexity of lipids, including SLs, is much greater than previously appreciated. SLs are generated de novo by four enzymes, namely serine palmitoyltransferase, 3-ketodihydrosphingosine reductase, ceramide synthase and dihydroceramide Δ4-desaturase 1. Some of these enzymes depend on the availability of specific substrates and cofactors, which are themselves supplied by other complex metabolic pathways. The evolution of these four enzymes is poorly understood and likely depends on the co-evolution of the metabolic pathways that supply the other essential reaction components. Here, we introduce the concept of the 'anteome', from the Latin ante ('before') to describe the network of metabolic ('omic') pathways that must have converged in order for these pathways to co-evolve and permit SL synthesis. We also suggest that the current origin of life and evolutionary models lack appropriate experimental support to explain the appearance of this complex metabolic pathway and its anteome.
现代细胞膜含有种类繁多、令人眼花缭乱的脂质，其中包括鞘脂（SLs）。质谱技术的进步使人们认识到，包括鞘脂在内的脂质的数量和组合复杂性比之前所认为的要大得多。鞘脂由四种酶从头合成，即丝氨酸棕榈酰转移酶、3-酮二氢鞘氨醇还原酶、神经酰胺合酶和二氢神经酰胺Δ4-去饱和酶1。其中一些酶依赖于特定底物和辅因子的供应，而这些底物和辅因子本身由其他复杂的代谢途径提供。这四种酶的进化情况鲜为人知，可能依赖于提供其他必需反应成分的代谢途径的共同进化。在这里我们引入“前体组”的概念，源自拉丁语ante（意为“之前”），用以描述为使这些途径能够共同进化并允许鞘脂合成而必须汇聚的代谢（“组学”）途径网络。我们还指出，当前的生命起源和进化模型缺乏适当的实验支持来解释这种复杂代谢途径及其前体组的出现。
