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鞘磷脂合酶2的多种活性产生含饱和脂肪酸和/或单不饱和脂肪酸的二酰基甘油。

Multiple activities of sphingomyelin synthase 2 generate saturated fatty acid- and/or monounsaturated fatty acid-containing diacylglycerol.

作者信息

Murakami Chiaki, Dilimulati Kamila, Atsuta-Tsunoda Kyoko, Kawai Takuma, Inomata Sho, Hijikata Yasuhisa, Sakai Hiromichi, Sakane Fumio

机构信息

Department of Chemistry, Graduate School of Science, Chiba University, Chiba, Japan; Institute for Advanced Academic Research, Chiba University, Chiba, Japan.

Department of Chemistry, Graduate School of Science, Chiba University, Chiba, Japan.

出版信息

J Biol Chem. 2024 Dec;300(12):107960. doi: 10.1016/j.jbc.2024.107960. Epub 2024 Nov 5.

DOI:10.1016/j.jbc.2024.107960
PMID:39510177
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11663969/
Abstract

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, Zn 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.

摘要

磷脂酰胆碱（PC）特异性磷脂酶C（PC-PLC）（EC 3.1.4.3）和磷脂酰乙醇胺（PE）特异性磷脂酶C（PE-PLC）（EC 3.1.4.62）可生成二酰基甘油（DG）且对三环癸烷-9-基-黄原酸酯（D609）敏感，分别于大约70年前和35年前在哺乳动物组织的去污剂不溶性组分中被检测到。然而，参与PC-PLC和PE-PLC活性的基因和蛋白质仍不清楚。在最近的一项研究中，我们观察到哺乳动物鞘磷脂合酶（SMS）1和SMS相关蛋白在体外具有PC-PLC和PE-PLC活性。在本研究中，我们表明位于质膜去污剂不溶性组分中的人SMS2也具有PC-PLC活性（约为SMS活性的41%）、PE-PLC活性（约为4%）、神经酰胺磷酸乙醇胺合酶（CPES）活性（约为46%）以及在磷脂-去污剂混合胶束存在下的SMS活性。此外，在无去污剂的蛋白脂质体（接近天然环境）中重构的纯化SMS2显示出PC-PLC、PE-PLC和CPES活性。值得注意的是,在存在约2摩尔%神经酰胺和4摩尔%PC（1:2比例）的情况下，PC-PLC活性几乎与SMS活性相等。作为PC/PE-PLC的SMS2对含饱和脂肪酸和/或单不饱和脂肪酸的PC和PE种类表现出底物选择性。PC-PLC/SMS抑制剂D609抑制了SMS2的所有酶活性（SMS活性、PC-PLC活性、PE-PLC活性和CPES活性）。此外，锌强烈抑制SMS2的所有酶活性。有趣的是，二酰基甘油抑制了SMS2的SMS活性（反馈控制）。这些结果表明，哺乳动物SMS2具有独特的酶学性质，是长期寻找的哺乳动物PC/PE-PLC的候选者。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/3c0fb2f7d384/gr14.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/8a8178c5927f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/080e982f3683/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/02e93dc05d00/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/ee668b343359/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/4c29515b51be/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/921dbf137f53/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/bcd481c37333/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/312d5c0ad9ca/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/a9302a614822/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/c45fc249229f/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/3e6ffdf2d876/gr11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/77d6be561ffd/gr12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/3b370a1dc343/gr13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47f2/11663969/3c0fb2f7d384/gr14.jpg

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