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Metabolism of sphingadiene and characterization of the sphingadiene-producing enzyme FADS3
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| Title: | Metabolism of sphingadiene and characterization of the sphingadiene-producing enzyme FADS3 |
| Authors: | Jojima, Keisuke Browse this author | | Kihara, Akio Browse this author →KAKEN DB |
| Keywords: | Ceramide | | Desaturase | | Lipid metabolism | | 4,14-Sphingadiene | | Sphingolipid |
| Issue Date: | 18-May-2023 |
| Publisher: | Elsevier |
| Journal Title: | Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids |
| Volume: | 1868 |
| Issue: | 8 |
| Start Page: | 159335 |
| Publisher DOI: | 10.1016/j.bbalip.2023.159335 |
| Abstract: | Of the long-chain bases (LCBs) that comprise the ceramides (CERs) present in mammals, only 4,14-sphingadiene (sphingadiene; SPD) has a cis double bond (at C14). Because of this unique structure, the metabolism of SPD may differ from that of other LCBs, but whether this is the case remains unclear. FADS3 is responsible for introducing the cis double bond in SPD. However, the substrate specificity of FADS3 and cofactors involved in the FADS3catalyzed reaction are also unknown. In the present study, a cell-based assay using a ceramide synthase inhibitor and an in vitro experiment showed that FADS3 is active toward sphingosine (SPH)-containing CERs (SPHCERs) but not toward free SPH. FADS3 exhibits specificity with respect to the chain length of the SPH moiety of SPH-CERs (active toward C16-20), but not that of the fatty acid moiety. Furthermore, FADS3 is active toward straight-chain and iso-branched-chain SPH-containing CERs but not toward anteiso-branched forms. In addition to SPH-CERs, FADS3 also shows activity toward dihydrosphingosine-containing CERs, but this activity is approximately half of that toward SPH-CERs. It uses either NADH or NADPH as an electron donor, and the electron transfer is facilitated by cytochrome b5. The metabolic flow of SPD to sphingomyelin is predominant over that to glycosphingolipids. In the metabolic pathway from SPD to fatty acids, the chain length of the SPD is reduced by two carbons and the trans double bond at C4 is saturated. This study thus elucidates the enzymatic properties of FADS3 and the metabolism of SPD. |
| Rights: | © 2023. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/92584 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 木原 章雄
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