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The Sjögren-Larsson Syndrome Gene Encodes a Hexadecenal Dehydrogenase of the Sphingosine 1-Phosphate Degradation Pathway
| Title: | The Sjögren-Larsson Syndrome Gene Encodes a Hexadecenal Dehydrogenase of the Sphingosine 1-Phosphate Degradation Pathway |
| Authors: | Nakahara, Kanae Browse this author | | Ohkuni, Aya Browse this author | | Kitamura, Takuya Browse this author | | Abe, Kensuke Browse this author | | Naganuma, Tatsuro Browse this author | | Ohno, Yusuke Browse this author | | Zoeller, Raphael A. Browse this author | | Kihara, Akio Browse this author →KAKEN DB |
| Issue Date: | 25-May-2012 |
| Publisher: | Elsevier |
| Journal Title: | Molecular Cell |
| Volume: | 46 |
| Issue: | 4 |
| Start Page: | 461 |
| End Page: | 471 |
| Publisher DOI: | 10.1016/j.molcel.2012.04.033 |
| PMID: | 22633490 |
| Abstract: | Sphingosine 1-phosphate (SIP) functions not only as a bioactive lipid molecule but also as an important intermediate of the sole sphingolipid-to-glycerolipid metabolic pathway. However, the precise reactions and the enzymes involved in this pathway remain unresolved. We report here that yeast HFD1 and the Sjögren-Larsson syndrome (SLS)-causative mammalian gene ALDH3A2 catalyze conversion of the S1P degradation product hexadecenal to hexadecenoic acid. The absence of ALDH3A2 in CHO-K1 mutant cells caused abnormal metabolism of S1P/hexadecenal to ether-linked glycerolipids. Moreover, we demonstrate that yeast Faa1 and Faa4 and mammalian ACSL family members are acyl-CoA synthetases involved in the sphingolipid-to-glycerolipid metabolic pathway, and that hexadecenoic acid accumulates in Δfaa1 Δfaa4 mutant cells. These results unveil the entire S1P metabolic pathway: S1P is metabolized to glycerolipids via hexadecenal, hexadecenoic acid, hexadecenoyl-CoA, and palmitoyl-CoA. From our results we propose a possibility that accumulation of the S1P metabolite hexadecenal contributes to the pathogenesis of SLS. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/49428 |
| 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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