Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC 3010, Australia.
Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC 3010, Australia.
Biochem Pharmacol. 2023 Jul;213:115621. doi: 10.1016/j.bcp.2023.115621. Epub 2023 May 20.
Mammalian cells contain more than a thousand different glycerophospholipid species that are essential membrane components and signalling molecules, with phosphatidylserine (PS) giving membranes their negative surface charge. Depending on the tissue, PS is important in apoptosis, blood clotting, cancer pathogenesis, as well as muscle and brain function, processes that are dependent on the asymmetrical distribution of PS on the plasma membrane and/or the capacity of PS to act as anchorage for various signalling proteins. Recent studies have implicated hepatic PS in the progression of non-alcoholic fatty liver disease (NAFLD), either as beneficial in the context of suppressing hepatic steatosis and fibrosis, or on the other hand as a potential contributor to the progression of liver cancer. This review provides an extensive overview of hepatic phospholipid metabolism, including its biosynthetic pathways, intracellular trafficking and roles in health and disease, further taking a deeper dive into PS metabolism, including associate and causative evidence of the role of PS in advanced liver disease.
哺乳动物细胞中含有超过一千种不同的甘油磷脂种类,它们是膜的重要组成部分和信号分子,其中磷脂酰丝氨酸(PS)赋予膜负的表面电荷。根据组织的不同,PS 在细胞凋亡、血液凝固、癌症发病机制以及肌肉和大脑功能中起着重要作用,这些过程依赖于 PS 在质膜上的不对称分布和/或 PS 作为各种信号蛋白锚定的能力。最近的研究表明,肝脏 PS 参与了非酒精性脂肪性肝病(NAFLD)的进展,其在抑制肝脂肪变性和纤维化的情况下可能是有益的,或者在另一方面可能是肝癌进展的潜在因素。本文综述了肝脏磷脂代谢,包括其生物合成途径、细胞内运输以及在健康和疾病中的作用,进一步深入探讨了 PS 代谢,包括 PS 在晚期肝病中的作用的相关和因果证据。