Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Curr Mol Med. 2010 Jul;10(5):454-66. doi: 10.2174/156652410791608225.
One of the most intriguing enzymes of sphingolipid biology is acid sphingomyelinase (ASMase). In a phospholipase C reaction, ASMase catalyzes the cleavage of the phosphocholine head group of sphingomyelin to generate ceramide. Cumulative efforts of various laboratories over the past 40 years have placed ASMase and its product ceramide at the forefront of lipid research. Activation of the ASMase/ceramide pathway is a shared response to an ever-growing list of receptor and non-receptor mediated forms of cellular stress including: death ligands (TNFalpha, TRAIL, Fas ligand), cytokines (IL-1, IFNgamma), radiation, pathogenic infections, cytotoxic agents and others. The strategic role of ASMase in lipid metabolism and cellular stress response has sparked interest in investigatig the molecular mechanisms underlying ASMase activation. In this article, we review the translational role of the ASMase/ceramide pathway and recent advances on its mechanisms of regulation.
鞘氨醇脂质生物学中最引人关注的酶之一是酸性鞘磷脂酶（ASMase）。在磷脂酶 C 反应中，ASMase 催化鞘磷脂的磷酸胆碱头部基团裂解，生成神经酰胺。过去 40 年来，各个实验室的不懈努力将 ASMase 及其产物神经酰胺置于脂质研究的前沿。ASMase/神经酰胺途径的激活是对越来越多的受体和非受体介导的细胞应激形式的共同反应，包括：死亡配体（TNFalpha、TRAIL、Fas 配体）、细胞因子（IL-1、IFNgamma）、辐射、致病性感染、细胞毒性剂等。ASMase 在脂质代谢和细胞应激反应中的战略作用激发了人们对研究 ASMase 激活的分子机制的兴趣。在本文中，我们回顾了 ASMase/神经酰胺途径的转化作用及其调控机制的最新进展。
