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

Nat Commun. 2014 Oct 27;5:5338. doi: 10.1038/ncomms6338.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetate-CoA Ligase / metabolism
  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Fatty Acids / metabolism*
  • HEK293 Cells
  • Humans
  • Lyases / metabolism
  • Metabolic Networks and Pathways*
  • Mice
  • Molecular Sequence Data
  • Palmitic Acids / metabolism
  • Phosphates / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sphingolipids / chemistry
  • Sphingolipids / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / chemistry
  • Sphingosine / metabolism

Substances

  • Fatty Acids
  • Palmitic Acids
  • Phosphates
  • Saccharomyces cerevisiae Proteins
  • Sphingolipids
  • 2-hydroxyhexadecanoic acid
  • Lyases
  • Acetate-CoA Ligase
  • phytosphingosine
  • Sphingosine