Academic Journal
Multiple activities of sphingomyelin synthase 2 generate saturated fatty acid- and/or monounsaturated fatty acid-containing diacylglycerol.
| العنوان: | Multiple activities of sphingomyelin synthase 2 generate saturated fatty acid- and/or monounsaturated fatty acid-containing diacylglycerol. |
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| المؤلفون: | Murakami, Chiaki, Dilimulati, Kamila, Atsuta-Tsunoda, Kyoko, Kawai, Takuma, Inomata, Sho, Hijikata, Yasuhisa, Sakai, Hiromichi, Sakane, Fumio |
| المصدر: | J Biol Chem ; ISSN:1083-351X ; Volume:300 ; Issue:12 |
| بيانات النشر: | Elsevier Science |
| سنة النشر: | 2024 |
| المجموعة: | PubMed Central (PMC) |
| مصطلحات موضوعية: | D609, ceramide, ceramide phosphoethanolamine synthase, diacylglycerol, phosphatidylcholine-phospholipase C, phosphatidylethanolamine-phospholipase C, phospholipase C, sphingomyelin synthase |
| الوصف: | Phosphatidylcholine (PC)-specific phospholipase C (PC-PLC) (EC 3.1.4.3) and phosphatidylethanolamine (PE)-specific PLC (PE-PLC) (EC 3.1.4.62), which generate diacylglycerol (DG) and are tricyclodecan-9-yl-xanthogenate (D609)-sensitive, were detected in detergent-insoluble fractions of mammalian tissues approximately 70 and 35 years ago, respectively. However, the genes and proteins involved in PC-PLC and PE-PLC activities remain unknown. In a recent study, we observed that mammalian sphingomyelin synthase (SMS) 1 and SMS-related protein display PC-PLC and PE-PLC activities in vitro. In the present study, we showed that human SMS2, which is located in detergent-insoluble fractions of the plasma membrane, also possesses PC-PLC activity (approximately 41% of SMS activity), PE-PLC activity (approximately 4%), ceramide phosphoethanolamine synthase (CPES) activity (approximately 46%), and SMS activity in the presence of phospholipid-detergent mixed micelles. Moreover, purified SMS2 reconstituted in detergent-free proteoliposomes (near-native environments) showed PC-PLC, PE-PLC, and CPES activities. Notably, in the presence of approximately 2 mol% ceramide and 4 mol% PC (1:2 ratio), PC-PLC activity was almost equal to SMS activity. SMS2 as PC/PE-PLC showed substrate selectivity for saturated fatty acid- and/or monounsaturated fatty acid-containing PC and PE species. The PC-PLC/SMS inhibitor D609 inhibited all enzyme activities (SMS, PC-PLC, PE-PLC, and CPES) of SMS2. Moreover, Zn2+ strongly inhibited all the enzymatic activities of SMS2. Interestingly, diacylglycerol inhibited the SMS activity of SMS2 (feedback control). These results indicate that mammalian SMS2 has unique enzymatic properties and is a candidate for a long-sought mammalian PC/PE-PLC. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://doi.org/10.1016/j.jbc.2024.107960; https://pubmed.ncbi.nlm.nih.gov/39510177; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663969/ |
| DOI: | 10.1016/j.jbc.2024.107960 |
| الاتاحة: | https://doi.org/10.1016/j.jbc.2024.107960 https://pubmed.ncbi.nlm.nih.gov/39510177 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663969/ |
| Rights: | Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. |
| رقم الانضمام: | edsbas.E74CFE64 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jbc.2024.107960 |
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