Lysophosphatidylcholine metabolism in Saccharomyces cerevisiae

The role of P-type ATPases in transport and a broad specificity acyltransferase in acylation

Wayne Riekhof, James Wu, Miguel A. Gijón, Simona Zarini, Robert C. Murphy, Dennis R. Voelker

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Abstract

We recently described a new route for the synthesis of phosphatidylethanolamine (PtdEtn) from exogenous lyso-PtdEtn, which we have termed the exogenous lysolipid metabolism (ELM) pathway. The ELM pathway for lyso-PtdEtn requires the action of plasma membrane P-type ATPases Dnf1p and Dnf2p and their requisite β-subunit, Lem3p, for the active uptake of lyso-PtdEtn. In addition, the acyl-CoA-dependent acyltransferase, Ale1p, mediates the acylation of the imported lysolipid to form PtdEtn. We now report that these components of the lyso-PtdEtn ELM pathway are also active with lyso-1-acyl-2-hydroxyl-sn-glycero-3-phosphocholine (PtdCho) as a substrate. Lyso-PtdCho supports the growth of a choline auxotrophic pem1Δ pem2Δ strain. Uptake of radiolabeled lyso-PtdCho was impaired by the dnf2Δ and lem3Δ mutations. Introduction of a lem3Δ mutation into a pem1Δ pem2Δ background impaired the ability of the resulting strain to grow with lyso-PtdCho as the sole precursor of PtdCho. After import of lyso-PtdCho, the recently characterized lyso-PtdEtn acyltransferase, Ale1p, functioned as the sole lyso-PtdCho acyltransferase in yeast. A pem1Δ pem2Δ ale1Δ strain grew with lyso-PtdCho as a substrate but showed a profound reduction in PtdCho content when lyso-PtdCho was the only precursor of PtdCho. Ale1p acylates lyso-PtdCho with a preference for monounsaturated acyl-CoA species, and the specific LPCAT activity of Ale1p in yeast membranes is >50-fold higher than the basal rate of de novo aminoglycerophospholipid biosynthesis from phosphatidylserine synthase activity. In addition to lyso-PtdCho, lyso-PtdEtn, and lyso-phosphatidic acid, Ale1p was also active with lysophosphatidylserine, lysophosphatidylglycerol, and lysophosphatidylinositol as substrates. These results establish a new pathway for the net synthesis of PtdCho in yeast and provide new tools for the study of PtdCho synthesis, transport, and remodeling.

Original languageEnglish (US)
Pages (from-to)36853-36861
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number51
DOIs
StatePublished - Dec 21 2007

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Acyltransferases
Acylation
Lysophosphatidylcholines
Metabolism
Yeast
Saccharomyces cerevisiae
Adenosine Triphosphatases
Acyl Coenzyme A
Yeasts
CDPdiacylglycerol-Serine O-Phosphatidyltransferase
Substrates
Phosphatidic Acids
Mutation
Phosphorylcholine
phosphatidylethanolamine
Biosynthesis
Cell membranes
Choline
Hydroxyl Radical
Cell Membrane

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lysophosphatidylcholine metabolism in Saccharomyces cerevisiae : The role of P-type ATPases in transport and a broad specificity acyltransferase in acylation. / Riekhof, Wayne; Wu, James; Gijón, Miguel A.; Zarini, Simona; Murphy, Robert C.; Voelker, Dennis R.

In: Journal of Biological Chemistry, Vol. 282, No. 51, 21.12.2007, p. 36853-36861.

Research output: Contribution to journalArticle

Riekhof, Wayne ; Wu, James ; Gijón, Miguel A. ; Zarini, Simona ; Murphy, Robert C. ; Voelker, Dennis R. / Lysophosphatidylcholine metabolism in Saccharomyces cerevisiae : The role of P-type ATPases in transport and a broad specificity acyltransferase in acylation. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 51. pp. 36853-36861.
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