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Sphingolipid Metabolism via Sphingosine 1-Phosphate and Its Role in Physiology, Pathology, and Nutrition

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Bioactive Lipid Mediators

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Abstract

A delicate balance between the synthesis and degradation of sphingolipids must be kept to maintain cellular sphingolipid levels. Otherwise, cellular functions are impaired, leading to various disorders. Complex sphingolipids are degraded to sphingosine by the actions of a series of lysosomal hydrolases, mutations in the genes of which are known to be responsible for approximately ten sphingolipid storage diseases to date. The resultant sphingosine is either recycled to sphingolipids or metabolized to glycerophospholipids via sphingosine 1-phosphate (S1P). Extracellular S1P is well known to be a lipid mediator, whereas intracellular S1P is a key intermediate of the sphingolipid metabolic pathway linking sphingolipids to glycerophospholipids. This pathway is important for sphingolipid homeostasis, and its impairment results in several harmful effects on cells and tissues. We have recently identified and described in detail the downstream metabolic pathway of S1P. S1P is metabolized to palmitoyl-CoA via trans-2-hexadecenal, trans-2-hexadecenoic acid, and trans-2-hexadecenoyl-CoA, and then incorporated into glycerophospholipids. One of the genes involved in this pathway is ALDH3A2, the causative gene of Sjögren–Larsson syndrome. This review focuses on the physiological, pathological, and nutritional aspects of S1P as an intermediate of the sphingolipid-metabolic pathway.

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Authors and Affiliations

  1. Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo, 060-0812, Japan

    Akio Kihara

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Correspondence to Akio Kihara .

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  1. Department of Biochemistry, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Takehiko Yokomizo

  2. Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

    Makoto Murakami

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Kihara, A. (2015). Sphingolipid Metabolism via Sphingosine 1-Phosphate and Its Role in Physiology, Pathology, and Nutrition. In: Yokomizo, T., Murakami, M. (eds) Bioactive Lipid Mediators. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55669-5_9

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