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

• Published in: Nature communications 2014-10, Vol.5 (1), p.5338-5338, Article 5338
• Main Authors: Kondo, Natsuki, Ohno, Yusuke, Yamagata, Maki, Obara, Takashi, Seki, Naoya, Kitamura, Takuya, Naganuma, Tatsuro, Kihara, Akio
• Format: Article
• Language: English
• Subjects: 13/106; 42/41; 631/443/319; 631/45/287/1183; 82/1; Acetate-CoA Ligase - metabolism; Amino Acid Sequence; Animals; CHO Cells; Cricetinae; Cricetulus; Fatty Acids - metabolism; HEK293 Cells; Humanities and Social Sciences; Humans; Lyases - metabolism; Metabolic Networks and Pathways; Mice; Molecular Sequence Data; multidisciplinary; Palmitic Acids - metabolism; Phosphates - metabolism; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - metabolism; Science; Science (multidisciplinary); Sphingolipids - chemistry; Sphingolipids - metabolism; Sphingosine - analogs & derivatives; Sphingosine - chemistry; Sphingosine - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms6338

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. Most cellular fatty acids contain even-numbered chains, and the origin of the small fraction of odd-numbered fatty acids remains unclear. Kondo et al. show that odd-numbered fatty acids are generated by metabolism of the long-chain base phytosphingosine in yeast and mammalian cells.