Department of Anatomy and Histology, Collegium Medicum, University of Zielona Góra, Zyty 28, 65-046 Zielona Góra, Poland.
Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.
Int J Mol Sci. 2024 Oct 6;25(19):10745. doi: 10.3390/ijms251910745.
Phospholipids are crucial structural components of cells. Phosphatidylcholine and phosphatidylethanolamine (both synthesized via the Kennedy pathway) and phosphatidylserine undergo interconversion. The dysregulation of this process is implicated in various diseases. This paper discusses the role of enzymes involved in the interconversion of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, specifically phosphatidylethanolamine N-methyltransferase (PEMT), phosphatidylserine synthases (PTDSS1 and PTDSS2), and phosphatidylserine decarboxylase (PISD), with a focus on their biochemical properties. Additionally, we describe the effects of the deregulation of these enzymes and their roles in both oncological and non-oncological diseases, including nonalcoholic fatty liver disease (NAFLD), Alzheimer's disease, obesity, insulin resistance, and type II diabetes. Current knowledge on inhibitors of these enzymes as potential therapeutic agents is also reviewed, although in most cases, inhibitors are yet to be developed. The final section of this article presents a bioinformatic analysis using the GEPIA portal to explore the significance of these enzymes in cancer processes.
磷脂是细胞的重要结构组成部分。磷酸甘油胆碱和磷脂乙醇胺(均通过肯尼思途径合成)和磷脂酰丝氨酸可相互转化。该过程的失调与各种疾病有关。本文讨论了参与磷酸甘油胆碱、磷脂乙醇胺和磷脂酰丝氨酸相互转化的酶的作用,特别是磷脂乙醇胺 N-甲基转移酶(PEMT)、磷脂酰丝氨酸合成酶(PTDSS1 和 PTDSS2)和磷脂酰丝氨酸脱羧酶(PISD),重点介绍它们的生化特性。此外,我们还描述了这些酶的失调及其在肿瘤和非肿瘤性疾病中的作用,包括非酒精性脂肪性肝病(NAFLD)、阿尔茨海默病、肥胖、胰岛素抵抗和 2 型糖尿病。还综述了这些酶作为潜在治疗剂的抑制剂的现有知识,尽管在大多数情况下,抑制剂尚未开发。本文的最后一部分使用 GEPIA 门户进行了生物信息学分析,以探讨这些酶在癌症过程中的意义。