Biochemistry and Diseases Related to the Interconversion of Phosphatidylcholine, Phosphatidylethanolamine, and Phosphatidylserine

Abstract

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.