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

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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)

Submitter: 木原 章雄

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