The Sj枚gren-Larsson Syndrome Gene Encodes a Hexadecenal Dehydrogenase of the Sphingosine 1-Phosphate Degradation Pathway

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• 作者：Kanae Nakahara¹ ; ³ ; Aya Ohkuni¹ ; ³ ; Takuya Kitamura¹ ; Kensuke Abe¹ ; Tatsuro Naganuma¹ ; Yusuke Ohno¹ ; Raphael  ; A. Zoeller² ; Akio Kihara¹ ; ^{kihara@pharm.hokudai.ac.jp}
• 刊名：Molecular Cell
• 出版年：2012
• 期刊代码：111_10972765
• 类别：bio
• 出版时间：25 May, 2012
• 卷：46
• 期：4
• 页码：461-471
• 文件大小：1004 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferences<h3 class="h3">Summaryh3>Sphingosine 1-phosphate (S1P) 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聽Sj枚gren-Larsson syndrome (SLS)-causative mammalian gene ALDH3A2 are responsible for conversion of聽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 螖faa1 螖faa4 mutant cells.聽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.