Identification of the phytosphingosine metabolic pathway leading to odd-numbered fatty acids

Natsuki Kondo, Yusuke Ohno, Maki Yamagata, Takashi Obara, Naoya Seki, Takuya Kitamura, Tatsuro Naganuma, Akio Kihara

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The long-chain base phytosphingosine is a component of sphingolipids and exists in yeast, plants and some mammalian tissues. Phytosphingosine is unique in that it possesses an additional hydroxyl group compared with other long-chain bases. However, its metabolism is unknown. Here we show that phytosphingosine is metabolized to odd-numbered fatty acids and is incorporated into glycerophospholipids both in yeast and mammalian cells. Disruption of the yeast gene encoding long-chain base 1-phosphate lyase, which catalyzes the committed step in the metabolism of phytosphingosine to glycerophospholipids, causes an ~40% reduction in the level of phosphatidylcholines that contain a C15 fatty acid. We also find that 2-hydroxypalmitic acid is an intermediate of the phytosphingosine metabolic pathway. Furthermore, we show that the yeast MPO1 gene, whose product belongs to a large, conserved protein family of unknown function, is involved in phytosphingosine metabolism. Our findings provide insights into fatty acid diversity and identify a pathway by which hydroxyl group-containing lipids are metabolized.

Original languageEnglish
Article number5338
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

phytosphingosine
yeast
fatty acids
Metabolic Networks and Pathways
metabolism
Fatty Acids
Yeast
Yeasts
Metabolism
genes
Glycerophospholipids
Hydroxyl Radical
lipids
phosphates
Sphingolipids
coding
Lyases
Gene encoding
proteins
Phosphatidylcholines

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)
  • Medicine(all)

Cite this

Kondo, N., Ohno, Y., Yamagata, M., Obara, T., Seki, N., Kitamura, T., ... Kihara, A. (2014). Identification of the phytosphingosine metabolic pathway leading to odd-numbered fatty acids. Nature Communications, 5, [5338]. https://doi.org/10.1038/ncomms6338

Identification of the phytosphingosine metabolic pathway leading to odd-numbered fatty acids. / Kondo, Natsuki; Ohno, Yusuke; Yamagata, Maki; Obara, Takashi; Seki, Naoya; Kitamura, Takuya; Naganuma, Tatsuro; Kihara, Akio.

In: Nature Communications, Vol. 5, 5338, 2014.

Research output: Contribution to journalArticle

Kondo, Natsuki ; Ohno, Yusuke ; Yamagata, Maki ; Obara, Takashi ; Seki, Naoya ; Kitamura, Takuya ; Naganuma, Tatsuro ; Kihara, Akio. / Identification of the phytosphingosine metabolic pathway leading to odd-numbered fatty acids. In: Nature Communications. 2014 ; Vol. 5.
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abstract = "The long-chain base phytosphingosine is a component of sphingolipids and exists in yeast, plants and some mammalian tissues. Phytosphingosine is unique in that it possesses an additional hydroxyl group compared with other long-chain bases. However, its metabolism is unknown. Here we show that phytosphingosine is metabolized to odd-numbered fatty acids and is incorporated into glycerophospholipids both in yeast and mammalian cells. Disruption of the yeast gene encoding long-chain base 1-phosphate lyase, which catalyzes the committed step in the metabolism of phytosphingosine to glycerophospholipids, causes an ~40{\%} reduction in the level of phosphatidylcholines that contain a C15 fatty acid. We also find that 2-hydroxypalmitic acid is an intermediate of the phytosphingosine metabolic pathway. Furthermore, we show that the yeast MPO1 gene, whose product belongs to a large, conserved protein family of unknown function, is involved in phytosphingosine metabolism. Our findings provide insights into fatty acid diversity and identify a pathway by which hydroxyl group-containing lipids are metabolized.",
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