학술논문
Human sphingomyelin synthase 1 generates diacylglycerol in the presence and absence of ceramide via multiple enzymatic activities.
Document Type
Article
Author
Source
Subject
*CERAMIDES
*SPHINGOMYELIN
*DEAFNESS
*LIPODYSTROPHY
*LECITHIN
*
*
*
*
Language
ISSN
0014-5793
Abstract
Sphingomyelin (SM) synthase 1 (SMS1), which is involved in lipodystrophy, deafness, and thrombasthenia, generates diacylglycerol (DG) and SM using phosphatidylcholine (PC) and ceramide as substrates. Here, we found that SMS1 possesses DG‐generating activities via hydrolysis of PC and phosphatidylethanolamine (PE) in the absence of ceramide and ceramide phosphoethanolamine synthase (CPES) activity. In the presence of the same concentration (4.7 mol%) of PC and ceramide, the amounts of DG produced by SMS and PC‐phospholipase C (PLC) activities of SMS1 were approximately 65% and 35% of total DG production, respectively. PC‐PLC activity showed substrate selectivity for saturated and/or monounsaturated fatty acid‐containing PC species. A PC‐PLC/SMS inhibitor, D609, inhibited only SMS activity. Mn2+ inhibited only PC‐PLC activity. Intriguingly, DG attenuated SMS/CPES activities. Our study indicates that SMS1 is a unique enzyme with PC‐PLC/PE‐PLC/SMS/CPES activities. [ABSTRACT FROM AUTHOR]