The Sjögren-Larsson Syndrome Gene Encodes a Hexadecenal Dehydrogenase of the Sphingosine 1-Phosphate Degradation Pathway
| Autor: | Kensuke Abe, Tatsuro Naganuma, Aya Ohkuni, Yusuke Ohno, Raphael A. Zoeller, Kanae Nakahara, Takuya Kitamura, Akio Kihara |
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| Rok vydání: | 2012 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Genes Fungal Mutant CHO Cells Palmitic Acids Saccharomyces cerevisiae Biology chemistry.chemical_compound Cricetulus Sphingosine Cricetinae Coenzyme A Ligases Animals Humans Sphingosine-1-phosphate Molecular Biology chemistry.chemical_classification Cell Biology Metabolism Aldehyde Oxidoreductases Yeast Sjogren-Larsson Syndrome Metabolic pathway Enzyme chemistry Hexadecenoic Acid Biochemistry Mutation lipids (amino acids peptides and proteins) Acyl Coenzyme A Lysophospholipids Metabolic Networks and Pathways |
| Zdroj: | Molecular Cell. 46:461-471 |
| ISSN: | 1097-2765 |
| Popis: | 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 Sjögren-Larsson syndrome (SLS)-causative mammalian gene ALDH3A2 are responsible for 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. |
| Databáze: | OpenAIRE |
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