Publications

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

  Kondo N., Ohno Y., Yamagata M., Obara T., Seki N., Kitamura T., Naganuma T., Kihara A.

  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 phyt ... >> More

  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. << Less

  Nat. Commun. 5:5338-5338(2014) [PubMed] [EuropePMC]

  This publication is cited by 6 other entries.

• Yeast Mpo1 is a novel dioxygenase that catalyzes the alpha-oxidation of a 2-hydroxy fatty acid in an Fe2+-dependent manner.

  Seki N., Mori K., Kitamura T., Miyamoto M., Kihara A.

  Phytosphingosine (PHS) is the major long-chain base component of sphingolipids in <i>Saccharomyces cerevisiae</i> The PHS metabolic pathway includes a fatty acid (FA) α-oxidation reaction. Recently, we identified the novel protein Mpo1, which is involved in PHS metabolism. However, the details of ... >> More

  Phytosphingosine (PHS) is the major long-chain base component of sphingolipids in <i>Saccharomyces cerevisiae</i> The PHS metabolic pathway includes a fatty acid (FA) α-oxidation reaction. Recently, we identified the novel protein Mpo1, which is involved in PHS metabolism. However, the details of the FA α-oxidation reaction and the role of Mpo1 in PHS metabolism remained unclear. In the present study, we revealed that Mpo1 is involved in the α-oxidation of 2-hydroxy (2-OH) palmitic acid (C_16:0-COOH) in the PHS metabolic pathway. Our <i>in vitro</i> assay revealed that not only the Mpo1-containing membrane fraction but also the soluble fraction was required for the α-oxidation of 2-OH C_16:0-COOH. The addition of Fe²⁺ eliminated the need for the soluble fraction. Purified Mpo1 converted 2-OH C_16:0-COOH to C_15:0-COOH in the presence of Fe²⁺, indicating that Mpo1 is the enzyme body responsible for catalyzing the FA α-oxidation reaction. This reaction was also found to require an oxygen molecule. Our findings indicate that Mpo1 catalyzes the FA α-oxidation reaction as 2-OH fatty acid dioxygenase, mediated by iron(IV) peroxide. Although numerous Mpo1 homologs exist in bacteria, fungi, protozoa, and plants, their functions had not yet been clarified. However, our findings suggest that these family members function as dioxygenases. << Less

  Mol. Cell. Biol. 39:0-0(2019) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.