School of Pharmacy, Fudan University, Shanghai, China.
Adv Exp Med Biol. 2022;1372:169-188. doi: 10.1007/978-981-19-0394-6_12.
Sphingolipids are the major lipid components on cellular membranes especially on lipid raft regions, intermediating various important biological functions for eukaryotic cells. Sphingolipid metabolism pathways can utilize sugar, protein, nucleic acid, and other metabolites participating lipid transport in the circulation, play an essential role in maintaining cell homeostasis and are related to a variety of different diseases including lysosomal storage disorders (LSDs), Gaucher disease, etc. The dynamic balance of sphingolipid levels in organisms is regulated by a series of sphingolipid synthases, hydrolases, and metabolic enzymes, such as sphingomyelinase (SMase), sphingomyelin synthase (SMS), serine palmitoyltransferase (SPT), ceramide synthase (CerS), glucosylceramide synthase (GCS), etc. Thus, sphingolipids and its related enzymes are potential targets for drug discoveries and receive great research interests by medicinal chemist. In this chapter, we will discuss the relationship between sphingolipids and the regulating enzymes involved in sphingolipid metabolisms, and systematically summarize the advances in the development of new drugs in the field.
鞘脂类是细胞膜的主要脂质成分，特别是在脂筏区域，介导体细胞的各种重要生物学功能。鞘脂代谢途径可以利用糖、蛋白质、核酸和其他代谢物参与循环中的脂质运输，在维持细胞内稳态方面发挥着重要作用，并与多种不同的疾病有关，包括溶酶体贮积症（LSDs）、戈谢病等。生物体中鞘脂水平的动态平衡由一系列鞘脂合成酶、水解酶和代谢酶调节，如神经鞘磷脂酶（SMase）、神经鞘磷脂合成酶（SMS）、丝氨酸棕榈酰转移酶（SPT）、神经酰胺合酶（CerS）、葡萄糖脑苷脂合酶（GCS）等。因此，鞘脂及其相关酶是药物发现的潜在靶点，受到药物化学家的广泛关注。在本章中，我们将讨论鞘脂与参与鞘脂代谢的调节酶之间的关系，并系统总结该领域新药开发的进展。
