Human sphingomyelin synthase 1 generates diacylglycerol in the presence and absence of ceramide via multiple enzymatic activities

Author:

Suzuki Rika1,Murakami Chiaki12ORCID,Dilimulati Kamila1ORCID,Atsuta‐Tsunoda Kyoko1,Kawai Takuma1,Sakane Fumio1ORCID

Affiliation:

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

2. Institute for Advanced Academic Research Chiba University Japan

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.

Funder

Hamaguchi Foundation for the Advancement of Biochemistry

Hokuto Foundation for Bioscience

Japan Foundation for Applied Enzymology

Japan Science Society

Japan Society for the Promotion of Science

Mishima Kaiun Memorial Foundation

Ono Medical Research Foundation

Sumitomo Foundation

Suzuken Memorial Foundation

Tojuro Iijima Foundation for Food Science and Technology

Toyo Suisan Foundation

Uehara Memorial Foundation

Publisher

Wiley

Subject

Cell Biology,Genetics,Molecular Biology,Biochemistry,Structural Biology,Biophysics

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